Some Question CIRM Grant Oversight as Excessive

The California stem cell agency is receiving “mixed reviews” for its oversight of its research grants, which now total $1 billion, according to an article today in The Scientist magazine.

Commonly governmental agencies are chastised for failing to ensure that taxpayer funds are spent effectively. In this case, the stem cell agency is being faulted -- by some -- for being too tough.

The case in point is the termination -- first reported by the California Stem Cell Report -- of three out of more than 300 grants. The amounts are tiny compared to the $3 billion that CIRM expects to give away, accounting for only $1.8 million in a $46 million round approved in 2007.

The Scientist article by Jef Akst said,

“Clearly, funding agencies need to offer some oversight of grants to avoid misuse of funds. But can there be too much of a good thing? “

She continued,

“There are mixed reviews among the scientific community about whether CIRM's close watch of their grantees is a good thing. To some, it is an important practice for public funding agencies such as CIRM to show the taxpayers that their money is going towards productive and fruitful research. 'I think the oversight is outstanding,' said John Simpson, the stem cell project director at the advocacy group Consumer Watchdog in California. 'It shows that they're not asleep at the switch. CIRM is functioning as both a grant making agency [and] also something of a steward of the funds it hands out.'

“But others say this kind of intense supervision can burden investigators -- and the science itself. 'In theory, it's a terrific thing,' agreed David Kaplan of Case Western Reserve University in Ohio, who has written about the peer review system at NIH. "To have the granting agency being involved enough to be helpful to their grantees, I think that is a terrific idea. The problem with that kind of a system is that you can be too intrusive. That eliminates that kind of serendipity [in scientific discovery].'“

Akst wrote that CIRM's “short timeline” may lie behind its grant monitoring, which is more rigorous than performed by the NIH.

She said,

“While the NIH will exist for many years to come, CIRM has a 10-year lifespan, as approved by California voters in 2004. 'CIRM has very defined goals,' said the Burnham Institute for Medical Research's Huei-Sheng Vincent Chen, another SEED grant recipient. '[They] wanted something within 10 years so they have to be more aggressive.'"

The Scientist magazine also chose to publish the names of the scientists whose grants were terminated. Their names are by law public record. Only one of the three scientists spoke with Akst, John Cooke of Stanford.

Akst's story said,

"'I anticipated that they would be happy with that [new] proposal,' Cooke recalled. 'But] they weren't happy.' In January 2009, after a second, more detailed progress report, follow up phone discussions, and a petition for reconsideration from Cooke, CIRM revoked his second year of funding -- nearly half of what he had originally been awarded -- citing the new directions his research had taken.

'I can understand their reasoning,' Cooke said. 'I just wish I had understood that that applied to the SEED grants.'"

Last month, CIRM approved $230 million for 14 grants up to $20 million each that appear to require even more rigorous oversight than earlier rounds. Some CIRM directors said publicly that they expect to see some of the latest grants terminated early because they will fail to meet the required benchmarks.

You can find a list here of all the items published on the California Stem Cell Report concerning the terminated grants. They include comments from the other two scientists, who we have chosen not to identify for previously discussed reasons.

$30 Million Available for Immunology Research

The California stem cell sweepstakes began another round this week with a $30 million jackpot for about 20 researchers.

CIRM is looking for applications from both research institutions and businesses as well as proposals for scientific collaboration with researchers from Germany and Australia.

This round will finance “transformative” research into cell transplantation immunology. The hope is that it will lead to development of immune tolerance of pluripotent stem cell derivatives and potential correction of autoimmunity.

Mandatory letters of intent are due Dec. 15. Winners should expect checks in the mail next summer.

Applications and details can be found here.

A Look at Tucson's Calimmune and $20 Milllion

The global headquarters of Calimmune, Inc., which shares in a $20 million grant from the California stem cell agency, stands on one of the more unlovely thoroughfares in Arizona.

The three-year-old firm is only a short walk on East Broadway in Tucson from O'Reilly Chevrolet and a Burger King. While Calimmune's address may not electrify folks on Wall Street, it has a pedigree that it is hard to quibble with.

By one account, Calimmune was founded by David Baltimore (see photo), a former member of the board of directors of the $3 billion California stem cell agency. Baltimore also is a Nobel Prize winner and former president of Caltech. Other accounts state that Irvin Chen, director of the UCLA AIDS Institute, was a co-founder.

Late last month, California's stem cell agency approved a $20 million grant to Chen and Geoff Symonds, chief scientific officer of Calimmune, a little-known company with no Web site but a laboratory in Australia, lab space in Pasadena, Ca., and more facilities soon to come at UCLA.

CIRM said the grant was aimed at generating an FDA application in four years for a clinical trial “to treat HIV/AIDS using an RNA interference approach to modify the patient’s blood-forming stem cells. When transplanted back, those cells will produce T cells that are resistant to HIV infection.”

The proposal echoes Calimmune goals articulated earlier on the Web site of Grayhawk Capital, a private equity investment company in Phoenix, Az., that has cash in Calimunne. Some initial research involving Symonds and UCLA was published last February with partial funding from Johnson & Johnson in Australia.

In response to email queries, Calimmune's CEO, Louis Breton, told the California Stem Cell Report that Symonds will perform his CIRM-funded work in California. He said the closely held firm is aware that CIRM is barred from funding out-of-state grants. Breton did not respond to questions about the number of Calimmune employees and their locations, although he said he anticipated more hiring for the CIRM grant. He said the Tucson location houses a small administrative staff. The company is incorporated in Delaware.

As for Calimmune's funding, we asked Breton whether any originated with Johnson & Johnson. Until the last year or so, Symonds was senior research director at Johnson & Johnson Research Pty Ltd. in Sydney, Australia, where the Calimmune lab is located. According to one report earlier this year, he holds more than $10,000 in Johnson & Johnson stock. At least one of the other Calimmune scientists in Australia worked as well for Johnson & Johnson until February. Breton, however, said none of the company's funding originated with Johnson & Johnson. Grayhawk did not respond our email query.

A Johnson & Johnson company document said in 2008 that the purpose of the Johnson & Johnson research operation involving Symonds was “to identify new medical discoveries in Australia and facilitate their commercial development into new products for Johnson & Johnson.”

CIRM reviewers were enthusiastic about Chen and Symonds disease team project. A CIRM summary of the application said,

“Reviewers stated that the resources and investigators are outstanding and the team is superb, both scientifically and in therapy development. The Disease Team comprises a collaboration between two complementary groups, one academic and one corporate. Each brings unique expertise to the project, with the academic group providing scientific know-how and proof of concept and the corporate group providing expertise in biologics development and commercialization. The team leaders are accomplished, highly productive investigators with a demonstrated track record in the field of HIV research, gene therapy, and/or clinical drug development. Key members of this team made the initial scientific observations leading to their hypothesis and demonstrated proof of concept in tissue culture and relevant models. A subset of the team has direct experience with a gene therapy trial in humans.”

Rundown on Grant Termination Stories

Our grant termination story last week is continuing to draw readers. However, other stories were carried as far back as last April. Here is a complete list of articles on the subject.

April 24, 2009
CIRM: Some Scientists' Grants to be Pulled
Some researchers who have been funded by California's $3 billion stem cell agency are going to lose their grants because of a lack of progress, according to a top CIRM official.

June 14, 2009
CIRM Pulls a Grant, Aggressive Monitoring Reported
In what appears to be a first, the California stem cell agency has pulled at least one grant from one of its researchers, apparently because of a lack of progress.

June 17, 2009
CIRM Pulls Three Grants from Researchers
SAN DIEGO -- The California stem cell agency tonight said it has terminated three research grants for lack of progress, but declined to release immediately the names of the researchers or the institutions involved.

Nov. 2, 2009
CIRM Scrutinizes Grantee Performance: The Tale of Three Terminations
Playing the rich uncle to California stem cell researchers is unquestionably satisfying, but the folks at the state's $3 billion stem cell agency sometimes bear messages for scientists that may be less than warmly received.

Text of Csete's Description of CIRM Grant Monitoring

CSCR Withholds Names of Terminated Grantees to Avoid Unnecessary Harm
The California Stem Cell Report is not naming the three scientists whose grants were terminated by the state's stem cell agency because doing so would unnecessarily damage their reputations.

CIRM as Regulator, Compliance Enforcer
In addition to handing out $3 billion in grants to California stem cell researchers, CIRM is also a regulator, monitoring the conduct of its grantees' research to ensure they adhere to the agency's stringent ethical standards.

Nov. 5, 2009
More on the Tale of Three Terminations
Some confusion has arisen in connection with a story in the Scientist magazine concerning our account of the termination of three grants by the California stem cell agency. In an attempt to clarify the situation, we are providing more information on the decision by the California Stem Cell Report to withhold the names of the researchers and also on the actions of the California stem cell agency.

Torres Hails CIRM Innovation, Leadership

The Sacramento Bee last week carried an op-ed piece by Art Torres, co-vice chairman of the $3 billion California stem cell agency, touting the virtues of CIRM, its innovation and the wisdom of the California electorate.

Torres, a former state legislator and former head of the state Democratic party, said,

"(The) drive to innovate is what led voters to create the California Institute for Regenerative Medicine and its charter to invest in stem cell research. The goal was clear: Keep California, its universities and biotech industry on the forefront of this most promising area of innovation in health care."

Torres focused particularly on CIRM's ambitious, $230 million disease team grant and loan effort, the largest research round in the agency's history.

Torress said,

"There are no other funding organizations in the country that are able to make this kind of investment in stem cell innovation."

He continued,

"We don't yet know what researchers will discover. But we do know that, whatever they discover, this new approach to science means we will be able to turn it into viable treatments for people much, much faster than ever before. That will move stem cells from the promise of new therapies to delivering on that promise for the people of California.

"And that's exactly what the voters wanted when they created CIRM: for it to reflect the innovative leadership that is this state."

Torres" piece drew only three comments online from readers. All were negative.

Off-topic: No White Whale

Regarding our Oct. 29, 2009, off-topic item about a whale attack on a sailboat, it now appears that it was a mere collision -- not an assault.

You can read the latest information in Latitude 38. See the "real story" item on this page. There is no guarantee that the story won't change again.

More on the Tale of Three Terminations

Some confusion has arisen in connection with a story in the Scientist magazine concerning our account of the termination of three grants by the California stem cell agency.

In an attempt to clarify the situation, we are providing more information on the decision by the California Stem Cell Report to withhold the names of the researchers and also on the actions of the California stem cell agency.

CIRM was slow to release the information, which by state law is public record, but the agency did not withhold it. Here is the string of events.

Last June, I was at the CIRM board meeting at which Marie Csete , then CIRM's chief scientific officer, gave her account of how the CIRM SEED grants were monitored. (CSCR carried the text of her remarks and those of directors in the four related items posted this week.)

At the meeting, I asked both the CIRM attorney, James Harrison, and the chief communications officer, Don Gibbons, for the names. They asked for a week or so delay in providing them in order to be sure the researchers had been told their names were public record and to discuss the matter with CIRM's executive committee. Given the potential impact on the researchers, that seemed appropriate.

Some weeks passed, and I still had not heard back. So I queried Gibbons by email concerning the names. He ultimately provided information that led to their identification.

Over the decades that I have spent as a reporter and editor, my practice then and now is to publish the names of individuals involved in public matters. In the case of CIRM, the agency leads an unprecedented, $6 billion (including interest) experiment with taxpayer dollars that could have a major impact on science, making it all the more important that the agency be critically examined.

That said, it is incumbent on journalists to consider the personal and professional impact of the publication of names on the individuals involved, many of whom are secondary to the matter at hand. In marginal cases, editors and reporters should weigh the pros and cons of such publication and whether the potential damage outweighs the possible public good. In this case, some of the questions for me were: Will better policy result if the individuals are identified? Was there wrongdoing? Is it unfair to single out these individuals while others who may be involved in more serious misdeeds (say for example, possibly some NIH grant recipients) remain anonymous?

Given current practices surrounding government research grants, public disclosure of the names in this case would carry a great potential for harm to the individuals and little public benefit. The problem is largely created by NIH grant monitoring practices, among others. As I understand it, the NIH rarely, if ever terminates a grant for lack of progress. When NIH grants are terminated, they appear to involve cases of malfeasance or some sort of wrongdoing. Such does not appear to be the case involving the three CIRM grants. However, the perception in the scientific community, right or wrong, is certain to be colored by the NIH approach. I also think it is fair to say that many CIRM researchers are not accustomed to CIRM's monitoring, particularly the three researchers, all of whom have long and respected careers.

Probably the most important question raised by this case is: Why does the NIH give away money and not monitor the grant progress much as CIRM does? CIRM Director Floyd Bloom, former editor-in-chief of Science magazine, said that under NIH practices a researcher is free to "change directions, convert personnel into equipment funds, and essentially re-program the proposed project." It may be stretching it a bit, but some folks from Enron and WorldCom are serving prison time for doing much the same thing.

As for CIRM's openness and transparency, given decades of experience with California state government, it is not much different than many state agencies, which is not a high hurdle. CIRM certainly could do better, especially considering the conflicts of interest that are built into its board.

The agency has pledged to adhere to the highest standards of openness but has fallen short of that measure, which goes beyond mere legal requirements. For example, CIRM's 29 directors and additional top management must file statements of economic interest under the state's conflict of interest laws. The governor of the state of California posts his statement online along with the top officials in his administration. CIRM does not meet that standard. Instead, interested parties must make a specific request for a public record that is not on the CIRM Web site. Responses on records requests sometimes take weeks and weeks. CIRM refuses to disclose in any form the economic interest reports from the reviewers who make the de facto decisions on grant applications. That makes it all but impossible for grant applicants or the public to determine if conflicts exist. CIRM also regularly fails to post important background material well in advance of its directors meeting, meaning that interested parties do not have enough time to comment intelligently or make plans to attend the meetings. More examples could be cited.

The Scientist story has generated little comment on its Web site, but one remark caught my eye today. Rafaela Canete-Soler said,

“The (monitoring and termination) policy at the CIRM seems to me timely and appropriate. By the tone of the article and the sentiments of the researchers, I can only express my admiration for them, as well as for CIRM and the way the evaluation seems to have taken place. We all know that projects and ideas do not always work the way that we had planned.

“I once heard that changes for the best almost always happen first in California, then in the United States and then in the rest of the world. The policy of NIH of liberty to take the research where it leads you does not appear to be sustainable any longer. For a very simple reason: resources are finite. Priorities and objectives, particularly those proposed by researcher, and for which they are funded, are to be followed up and nurtured within the framework of a sound and healthy competition system.”

The Podesta Watch: White House Visits, Red Shoes and 61 Percent Gains

Tony Podesta, the California stem cell agency's man on the Potomac, is making news again, largely for flashy fundraising and access to the Obama White House.

Podesta was hired as a federal lobbyist by CIRM last February under a 10-month, $240,000 contract. California state agencies, rarely if ever, hire federal lobbyists, although the state does maintain a lobbyist on the state payroll in Washingon.

Podesta visited the White House five times in six months, but the clients were not identified. Our guess is that they did not include CIRM. So far, CIRM Chairman Robert Klein has not reported publicly to his board of directors on what California taxpayers are receiving for their money. Podesta's contract with CIRM is due to expire in December but could be extended.

Here is a rundown on recent Podesta stories:

“Podestas Rule Washington and Obama Guest List” – US News and World Report – The story says it shows “the power of the Podesta family. Between them, Obama adviser and former Clinton Chief of Staff John Podesta; his brother, lobbyist Tony Podesta; and Tony's lobbying wife Heather made 25 visits. By comparison, House Speaker Nancy Pelosi made one visit.”

“Holdouts to Obama's Vow to Change” – Commentary by Albert R. Hunt, formerly of the Wall Street Journal and now of Bloomberg, “Heather and Tony Podesta are conscientious objectors to the culture of change in Washington. The husband and wife, with separate lobbying firms, are raking in millions from the insurance and drug industries, tobacco companies and corporate interests fighting changes to labor laws or the overhaul of the student-loan program.” In New York Times also.

Tony Podesta Scoops Up Nearly $19 million in Third Quarter, Up 61 percent – National Journal

"Tony Podesta has happy feet for 65th birthday” – Washington Examiner - Podesta and friends celebrate his birthday at a high-profile fete wearing red shoes.

“Big money buys seats at lawmakers' dinner tables” – Washington Times --Heather Podesta, wife of Tony and a lobbyist herself, throw fundraiser at her $2 million home

Then there is this paean to Heather Podesta in the Washington Post in August that had, as they say, tongues wagging along the Potomac.

Releasing the names of the White House visitors was a first. The Bush administration refused to do so. Initially Obama adopted that position but wisely changed his mind. The release of the list attracted a great deal of coverage because of its novelty but that will diminish.

Here is a link to the White House list of Podesta visits.

As readers may recall, we have raised questions about the effectiveness and propriety of CIRM's efforts to become a player in Washington politics. We do not object to CIRM making its voice heard in Congress nor particularly in Sacramento. But CIRM has more than enough laundry to take care of in the Golden State. Attempting to become a major influence in Washington will require funds and time that CIRM cannot afford.

Here is a link to one article on the subject. You can also search on the terms “podesta” and “lobbying.”

Scientist Magazine Picks Up Grant Termination Story

The Scientist magazine today picked up our report on the termination of three grants by the California stem cell agency.

In a piece by Jef Akst, the magazine said CIRM “giveth and it taketh away.”

The Scientist piece, which credited the California Stem Cell Report, did not add a great deal to our report, but Akst wrote,

"'Termination is a last option,'" CIRM's chief communications officer Don Gibbons wrote in an email to The Scientist. 'We first work with grantees who are not progressing to get them back on track.'"

Nature on Disease Team Round: The Race is On

Nature magazine has published another piece on the California stem cell agency's ambitious, $230 million disease team round, calling it the “starting gun” to confirm the promise of stem cells.

The Nov. 2, 2009, story by Erika Check Hayden said that some researchers around the country say the grants and loans will benefit the field as a whole. She also carried a comment from the former chairman of the CIRM grants review group, Stuart Orkin. Orkin resigned his post last November and did not participate in the review of the disease team grants.

Hayden wrote,

“Other researchers have welcomed the awards, but note that many of the projects test ideas that are similar to work being funded elsewhere.

"'The general [new-grant] portfolio strikes me as being similar to what is going on elsewhere,'" says haematologist Stuart Orkin of the Children's Hospital Boston in Massachusetts. 'I don't see anything radically different from what I see people thinking about in other institutions, but it's great to have the funding to do it.'

“For instance, two of the grants will fund work to develop monoclonal antibodies — targeted biological drugs that are already approved for many indications — to target cancer cells. Another grant will try to use a patient's own cardiac stem cells to repair damage from heart attacks, a controversial approach that is already being tested in patients. A fourth grant aims to modify patients' bone-marrow cells to correct the genetic defect that causes sickle-cell anaemia, then implant the cells back into patients.

“A similar approach has been used to treat severe combined immunodeficiency disorder. 'That would have been called gene therapy before, instead of stem-cell therapy, and there are a number of people doing that,' Orkin points out.”

The magazine also carried an item last week on its blog.

Don Gibbons, chief communications officer for CIRM, has pointed out that the grants received more coverage than we reported last week. We found another story in a local paper in Los Angeles, the Daily News, and one on a Los Angeles radio station, KPCC. The Daily News story was reprinted in the Contra Costa Times. Other stories appeared elsewhere as well.

In our reporting on news coverage of CIRM events, we rely on Internet search engines, which are not perfect and sometimes slow. Plus we do not necessarily mention every news report in our items, just the ones of interest with higher impact or interesting reporting or commentary.

CIRM has a standing invitation to comment on any subject, including accounts of CIRM news coverage, on the California Stem Cell Report. We have told the agency on more than one occasion we will carry their commentary verbatim, a practice that is not found in the mainstream media.

Correction

The “stem cell web” item Nov. 1, 2009, incorrectly reported that only one reporter was present at the CIRM disease team news conference, based on information provided by a person who was also present. CIRM says two other reporters from local outlets were also on the scene.

CIRM Scrutinizes Grantee Performance: The Tale of Three Terminations

Playing the rich uncle to California stem cell researchers is unquestionably satisfying, but the folks at the state's $3 billion stem cell agency sometimes bear messages for scientists that may be less than warmly received.

That's when they become regulators and stewards of the public's money. Particularly when they exercise that responsibility in a more rigorous way than is the practice at the NIH.

CIRM is not making much of the fact that it has revoked three grants because of a lack of progress. It took us more than a month to secure the identities of the researchers who fell under CIRM's scrutiny. The agency, however, should take pride in its oversight. It enhances the credibility of the $3 billion agency and serves notice to all grantees that CIRM is more than a sugar daddy and takes its responsibilities seriously.

Only four months ago, CIRM directors heard a report on monitoring of grants that merits attention following approval of the largest research grant round in the agency's five-year history. The $230 million in disease team grants pose special challenges for the tiny agency. Its staff, currently without a chief scientific officer, will be called on to make go, no-go decisions on continued funding as researchers hit or miss bench marks in projects involving as much as $20 million.

One can only imagine the ruckus if CIRM staff recommends that funding be halted on a $20 million, four-year grant involving such high-profile and respected institutions as UC San Francisco, UCLA, Stanford, Salk and City of Hope, among others.

CIRM opened the window a bit on its oversight of grants at the board meeting in San Diego last June. Marie Csete, then chief scientific officer for CIRM, described in a positive fashion her office's monitoring of the $45 million SEED program, the first ever research grants by CIRM. She said CIRM's efforts saved some grants that would have perished. But it took a question from director Ricardo Azziz, chairman of the Department of Obstetrics and Gynecology at Cedars-Sinai Medicial Center, to bring out the information that three grants had been terminated.

As for the issues raised during the monitoring, Csete said,

“In general, I have to say it was slow progress. It wasn't bad progress. And it allowed us to identify some issues that are, I think, endemic with a new agency and new ideas. Institutions had trouble getting lines for their investigators. People had trouble hiring post docs who were able to do the work. We had trouble getting some of the (grants) out the door for various reasons.”

CIRM director Floyd Bloom, former editor of Science magazine and executive director, science communication, at Scripps, praised Csete and her staff's work. He said,

“This kind of nurturing, interactive relationship with the PIs's is absolutely unique in the grant world. And so I think it's a wonderful thing that you've instituted. It's going to be a tremendous amount of additional work on your staff to be able to do that, but it's highly commendable, and it's going to make the difference between success or failure, particularly for these intermediate level of successful early experiments where they have to be encouraged to go on and push.”

We spoke by telephone with two scientists whose grants were revoked and exchanged email with the third, who was out of the country. None are particularly pleased about losing their grants, but their comments offer insight into the process. We are not identifying them in this piece. To do so would place an unnecessary onus on them, given the current practices in the scientific grant community and the different monitoring procedures at the NIH. None of the issues with the grants appear to involve malfeasance.

One of the researchers said he was “bitter” about CIRM's action, declaring it caused a “huge uproar” at his institution. (Prior to our conversation, we had heard unconfirmed reports about significant unhappiness on the part of recipient institutions.) This researcher said CIRM's monitoring practices were a departure from those of the NIH, which allows “the liberty to take the research where it leads you.” Nonetheless, he continues to support CIRM.

Another scientist said he parted “amicably” with CIRM but confirmed that its practices are different than the those of the NIH. (The NIH has not responded to our queries concerning how many grants it has revoked for lack of progress.)

This researcher told us,

“I think that it is very important for CIRM to closely monitor its grantees. As a California taxpayer, I want to know that state revenues supporting the CIRM effort are well utilized. Furthermore, CIRM (and its grantees) need to make good on the promise of translating the science of stem cell biology into novel therapies.”

The third told us in an email that his grant had been “prematurely terminated.” He said the work has been completed without the CIRM support and the research accepted for publication in a prestigious journal next year. He also called CIRM a “great organization” and expressed the hope that it will lead to “great cures.”

The round of grants that Csete reported on involved only $45 million, substantially less than the $230 million in the disease team round. The stakes are now much larger. Powerful teams, some international, will be at work. Impending clinical trials will also create a vision of handsome profits, in addition to hoped-for prestige and accolades. CIRM directors have indicated they expect some of the disease team grants to fail. But revoking funds for one of those grants or loans will require a lot of steel on the part of the CIRM staff.

Csete abruptly resigned from CIRM after the June meeting. Her departure and the workload at CIRM likely meant that some of the monitoring efforts were pushed back. Most of the work is done by science officers, but at crucial points, it requires the intervention of CIRM's highest level scientist.

In the wake of Csete's departure, CIRM President Alan Trounson created a new position, vice president for research and development. A search firm has been hired for $100,000 to help recruit a candidate who will make go, no-go decisions on the disease team round along with other grants. Trounson is hoping to find someone with substantial experience in the biotech industry.

Whoever fills the job should not only be something of a scientific diplomat but also be able to face the big dogs of stem cell science and tell them no. CIRM's first responsibility is to generate results for the people of California and to serve as ardent stewards of the public's money.

(Below is a transcript of the entire discussion by the CIRM board in June concerning Csete's monitoring effort. Also below is a piece concerning our decision not to publish the names of the scientists whose grants were revoked as well as another item dealing with CIRM's efforts to ensure compliance with its ethical and research standards.)

Editor's note: The California Stem Cell Report first published an item on the termination of CIRM grants last April. Here is a rundown on all the stories published on this site as of Nov. 9, 2009, concerning grant termination.

CSCR Withholds Names of Terminated Grantees to Avoid Unnecessary Harm

The California Stem Cell Report is not naming the three scientists whose grants were terminated by the state's stem cell agency because doing so would unnecessarily damage their reputations.

It is our understanding that none of the issues involved malfeasance. Additionally, CIRM's progress monitoring appears to be more rigorous than the standards applied by the NIH, whose practices have set benchmarks in the scientific community.

Publication of the names could create erroneous, negative perceptions about the individuals involved.

We made the decision not to publish their identifies after discussions with a number of individuals, including two of the researchers. In our past occupation as an editor at a mainstream newspaper, publication of their identities would have been pretty much of a foregone conclusion. But given that we are no longer constrained by newspaper standards, some of which are very good and some not so good, we did not want to mindlessly do something that would unnecessarily harm the three.

We also asked CIRM director Floyd Bloom, former editor of Science magazine and executive director, science communication at Scripps, for his thoughts on publication of the names. Here is how he responded.

“For NIH grants, after the grant is awarded, one writes a 'progress report' annually in what is termed a 'non-competitive' renewal. For the duration of the award, the investigator is free to follow leads, change directions, convert personnel into equipment funds, and essentially re-program the proposed project. Only if the PI seeks to renew that grant must the changes be justified.

“In process described to us in June by Marie Csete, the scientific staff are in frequent contact with our CIRM-supported PIs, assessing their progress towards the goals they were approved to pursue, and for several of our competitions with stated milestones, assessing whether that progress will get them to their milestones. Lack of progress can be sufficient grounds to terminate the funding, and apparently those are the 3 cases you mention. Since we are kept blind to the PI names and institutions when we decide to award funding, I don't see that it is constructive to CIRM or those PIs to disclose names after termination.”

Text of Csete's Description of CIRM Grant Monitoring

On June 17, 2009, Marie Csete, then chief scientific officer for the $3 billion California stem cell agency, briefed its directors in San Diego on how CIRM monitors the progress of its grantees. Following her presentation, one director asked her how many grants had been terminated because of lack of progress. Three, she replied.

Here is the transcript of her remarks and the discussion by directors. Here is a link to the slides that she used. They begin on p. 22 of the file.

Csete: I guess the last thing I'm supposed to speak about is our mechanism for looking at progress reports. And the first opportunity we had to aggregate data on this was for the SEED grants, which are now more or less in their second year of funding for most of the investigators. And as a reminder, I think all the way back a few years, this was a grant program designed to develop human embryonic stem cell biology in the state. And since it was early, it was more idea based rather than preliminary data-based, and we really hoped to attract nonstem cell biologists to the field as well as cell and developmental biologists who were working perhaps on other stem cells, but had not done human embryonic stem cell work.

As such, the seed grants were acknowledged to be rather high risk, high gain. And I was involved in the SEED grants as a reviewer. So I have insight into the process from the beginning even before I came here to CIRM. I have to say that the overwhelming message I want to leave you with here is that despite a slow start, that was the bump in the road, that the SEEDs are really overwhelmingly successful. And we looked this week to find that there are already 64 papers coming out of the SEED program even though, again, these were new investigators in this field.

So it is important also, thanks to Bettina (Stephen, a CIRM science officer), to remind you that progress reports are not just progress reports -- and this has been an education for both the science office and for our scientists – that they really serve as a focus of a way that the science officers and our grantees can have a point of communication. It also allows us to get a heads up on where the data is, on what papers are being submitted, on potential patents that are coming out. Also when we discuss the progress reports in the science office meeting, it allows us to match scientists from our individual portfolios with other scientists whose progress we're hearing about in the meeting. In general, I have to say that I've gotten a lot of positive feedback from our PI's about the interactions with our science officers and our grantees.

So this is the process that we've sort of come to. And I've condensed a very complex diagram that has arrows going out every which way. On the right(on a slide she presented), you have a lot of gold stars. And the gold stars is what usually happens. On the left I put symbols showing how much communication happens at each one of these steps. So for the vast majority of the progress reports, things look good, and we generate an NGAs(notice of grant approval) with the next year's funding on the SEED grants.

But what I'm showing you in the middle is what happens when we receive a progress report that's not satisfactory. So we did receive some where we saw that the projects were not advancing. They were slow. The vast majority were those gold stars that, you know, went right back for the second year of funding.

In general, I have to say it was slow progress. It wasn't bad progress. And it allowed us to identify some issues that are, I think, endemic with a new agency and new ideas. institutions had trouble getting lines for their investigators. People had trouble hiring post docs who were able to do the work. We had trouble getting some of the NGAs out the door for various reasons. So right away, by having a communication with the PI after the progress report was in, we could help them. We could intervene and make the right calls to try to get and kick start these programs.

When there was insufficient data for us to judge how much work had been done, the science officer would request supplemental data. That often required a couple of phone calls and a couple of exchanges of e-mail because, again, we were interested in hearing what people would normally not send in as a progress report: difficulty getting cell lines grown, difficulty doing certain kinds of experiments so that we could see common features across our SEED grantees and allow them to help each other.

When the supplemental data suggested that there was still insufficient progress, I would look at the report, and we also had discussions with the entire science office. At that point, if we couldn't come to a way to jump start a project, we would have a conference call with the PI, and at this point we'd bring in the institutional official as well, the science officer who has this PI in their portfolio, and I, and we would have another call to try to get this program back on track. And very often what that meant was that we made a plan with the investigator to give them some more time so that they could generate some data and try to pick up where the progress was slow. So the time differed depending on the problems that were there, hiring problems, for example. If after this time period another supplemental progress report comes in and there was inadequate progress, we decided that we would notify the investigator that the project just didn't seem to be going anywhere, that there was no real plan to get it back on track and that there was a potential for termination.

Again, the AOOs were all involved in this as well. and if there was no response within two weeks to that potential termination letter, then the grant was terminated and the second year's funding was not advanced.

So what did we learn from this process? We learned that it's critical for us to be working with the PIs to keep the grants on track and how appreciative the PIs are when we do work with them to keep them on track. By the way, we also found several grants that would not have gone on because the investigator was interested in not pursuing the original goal of the research and was going to drop the work. We felt that these areas were so critical for the ideas that were part of the seed program, that we found other investigators who were co-PIs or related to the grant to take over and worked with these new investigators and found mentorship to keep that work going. So it went in both directions. We saw adequate progress where the grants would not have gone on had we not intervened. And I think that this is a very interim report for you because the final success of the SEEDs will be seen over the next year when the final reports come back. We know that papers are going out. We know that research is proceeding apace now; I think much to the effort of each of the individual science officers who worked very closely with the grantees. But it will be important to evaluate how many new labs were brought into human embryonic stem cell and pluripotent stem cell research. And I should also say that a lot of the investigators left to their own devices would have stopped what they were doing with their SEED grants and simply gone on to derive ips cells, and we would have had no portfolio had we (not) been actively managing the grants. But most importantly, the success of this program will be determined on how these investigators go into others of our programs and other large-scale funded grants with the work that was developed from the SEED. And we already have success in that area. We're seeing that one SEED grantee continued on and got an early translation award from CIRM last month.

So overall we've had enormous success, I think, with the SEED program, and we're still in the middle of it. And we've learned a lot about process that will help us to be managing larger scale projects and to work with our investigators in a really positive way.

CIRM Chairman Robert Klein: So, Dr. Csete, will you remind us the number of SEED grants originally awarded?

Csete: Seventy-four.

Klein: So 74 grants, and we've seen 62 or 63 papers at this point.

Dr. Csete: Sixty-four papers.

Klein: So a very high level of productivity. Thank you very much.
Dr. Bloom?

Director Floyd Bloom: This kind of nurturing interactive relationship with the PIs is absolutely unique in the grant world. And so I think it's a wonderful thing that you've instituted. It's going to be a tremendous amount of additional work on your staff to be able to do that, but it's highly commendable, and it's going to make the difference between success or failure, particularly for these intermediate level of successful early experiments where they have to be encouraged to go on and push. So it's a wonderful thing you've done.

Director Ricardo Azziz: I just want to echo that, for starters. I think it takes a tremendous amount of work to help these investigators forward. Again, presumably, they are also very appreciative of your efforts. of the 74 applications, how many – you spoke about the process that you are going through -- how many have been terminated for nonproductivity?

Csete: Three.

Azziz: Three of the 74. Thank you.

Klein: Okay. any additional board comment? Thank you very much, Dr. Csete.

CIRM as Regulator, Compliance Enforcer

In addition to handing out $3 billion in grants to California stem cell researchers, CIRM is also a regulator, monitoring the conduct of its grantees' research to ensure they adhere to the agency's stringent ethical standards.

The subject came up briefly at last week's board meeting in Los Angeles and is expected to come up again at the board meeting in December.

Geoff Lomax, senior officer for medical and ethical standards, had prepared a presentation to discuss, among other things, the agency's research standards monitoring program. But it was caught in the hurly-burly surrounding the disease team applications and was delayed until the next board meeting.

However, his slides are available and provide an introduction to the scope of what CIRM calls its compliance program.

The effort includes financial tracking, reporting on publications and IP and examination of institutions' own oversight programs along with site visits.

Lomax's slides also said,

“CIRM provided recommendations to two institutions regarding the need for more explicit procedures and policies to govern their oversight programs.

“CIRM identified one patent that had not been reported; grantee has now addressed.

“CIRM has worked with two grantee institutions to ensure compliance with AALAC (animal care accreditation) requirements.”

Lomax's slides start with number 25 in this file.

A $230 Million California Stem Cell Web

The publicity last week from recipients of $230 million from the California stem cell agency portrays an impressive web of scientists in the Golden State and beyond.

The list below began as a simple update of an earlier item with links to news releases from the beneficiaries of CIRM largess, in this case the agency's largest ever research round. But, as we gathered the information, what became abundantly clear are the significant financial and scientific ties between institutions that might seem to be rivals under other circumstances.

No doubt they continue to compete in other areas and will be competitors in the future for grants, talent and more. But in this case researchers put together powerful teams that won tens of millions of dollars for themselves and their institutions.

The releases from the institutions contain more information about the researchers and their projects than is contained in CIRM's press release on the disease team grants. But CIRM also provides separately summaries of the scientific reviews of the applications, which carry analysis, criticism and praise of the proposals.

Here is the latest list of news releases issued by the institutions and businesses.

Beckman Institute, shares $15 million with City of Hope and USC

Burnham Institute, no news release available, shares $19 million with UC San Francisco and Ludwig Institute

Calimmune, Inc., of Tucson, Az, no news release available, shares $20 million with UCLA

Cedars of Sinai Medical Center, $6 million

Children's Hospital, Los Angeles, no news release available, shares $9 million with UCLA

City of Hope, $18 million and shares $15 million with USC and Beckman Institute

Ludwig Institute for Cancer Research, no news release available, shares $19 million with UC San Francisco and Burnham, $16 million with Salk and UC San Diego

Novocell, shares $20 million with UC San Francisco

Salk Institute. shares $16 million with UC San Diego and Ludwig Institute

Sangamo Biosciences, Inc., of Richmond, Ca., shares $15 million with City of Hope

Stanford, $32 million, and shares $20 million with UCLA and USC, $20 million with UCLA

UCLA, shares $20 million with Calimmune, Inc., of Tucson, Az.; $9 million with Children's Hospital, Los Angeles; $20 million with Stanford and USC; $20 million with Stanford

UC San Diego, $20 million , shares $16 million with Salk and Ludwig

UC San Francisco, shares $39 million with Ludwig Institute, Novocell and Burnham

UC Santa Barbara, shares $16 million with USC

The international partners listed in the CIRM news release are the Medical Research Council of the United Kingdom($8 million via the Weatherall Institute of Molecular Medicine, Oxford University, no news release available from Weatherall); the University Health Network ($35 million)of Toronto, Canada.

Here is a link to CIRM's disesease team press package, including a video of the lengthy news conference. Only one reporter from a major publication was present at the news conference, Andy Pollack of the New York Times. No television stations sent crews.

(Editor's note: The earlier item that we posted concerning the institutional press releases has vanished from this Web site for reasons probably only fully understood by Google, which provides the blogging service that we use. Also, an earlier version of this item incorrectly said Pollack was the only reporter present at the news conference. CIRM reports that two other reporters from local outlets were on the scene.)

Correction

The “Loan” item on Oct. 29, 2009, misspelled the last name of Alex Lash as Kash.

Off-Topic: Shades of Moby Dick

Stories are told from time to time and then retold and retold about whales attacking sailboats. Some of them sound fanciful and are third and fourth hand.

Here is a current account of what appears to be a genuine attack by whales or whales on a sailboat yesterday off the Baja California coast. The boat sank in a matter of minutes but no one was seriously injured.

This is the first verifiable whale attack that we have heard about off the Mexican coast in 11 years of sailing here.

Blogger Talks to Novocell About First CIRM Loan

Little information was dispensed yesterday by the California stem cell agency about the first step in what is proposed to be a $500 million loan program for the biotech industry.

But a biopharmaceutical industry blogger provided some information about the $20 million loan to Novocell, Inc., a San Diego stem cell engineering company with an emphasis on diabetes therapies. It is the first beneficiary of the loan program.

CIRM directors approved the loan to help develop a novel cellular therapy for diabetes. The disease team effort includes a $2.8 million Novocell contract with Jeff Bluestone of UC San Francisco.

Alex Lash of the In Vivo blog talked to Novocell CEO John West. Kash wrote,

“West...says the cash infusion from 'the stem-cell experts' was a validation of the firm's work and puts it in a 'good position' to look for its next round of venture funding.

“There are some minor details to work out first, though. West says Novocell hasn't yet received a loan document from CIRM and isn't exactly sure about the terms. Based on the loan program's guidelines, West is aiming for 10% warrant coverage and a payback period closer to 10 years, the far end of the range. 'We have a good feeling we'll work it out,' said West.

“CIRM loans will certainly have more generous terms than typical bank loans, and the agency has said it doesn't expect many of them to be paid back. West said he was surprised that Novocell was the only for-profit to lead a disease team application. But he noted that not many of the state's stem-cell related firms were far enough along to push a program into the clinic within four years, one of the top criteria of the agency's reviewers.”

(Editor's note: An earlier version of this item misspelled Alex Lash's last name as Kash.)

Disease Team News Coverage, Irony and a 'Sinking' State

The California stem cell agency's $230 million disease team research effort, which boosted CIRM's spending beyond $1 billion, attracted moderate news coverage this morning and late yesterday.

Some publications, however, appeared to ignore the story entirely, including the Los Angeles Times and The Sacramento Bee, based on our Internet searches. The performance of the Times was particularly strange since more than $80 million is going to institutions in that area.

The San Francisco Chronicle published a page one story by Erin Allday, who listed all the approved programs and interviewed some scientists. She quoted CIRM director Jeff Sheehy as saying,

"These are not well-placed bets. These are carefully considered projects. We are not casually throwing away money hoping we'll get a cure at the end of the day. We're moving forward aggressively but with a rigorous review of science."

The Chronicle, New York Times, Nature and the San Diego Union-Tribune all noted that most of the disease team grants do not involve human embryonic stem cell research, which was the rallying cry for Prop. 71, the political device that created CIRM. Thomas Kupper of the San Diego paper called that fact ironic.

One sharp-tongued blogger, Wesley J. Smith of “Second Hand Smoke,” wrote,

“So, do I now think that the CIRM is peachy keen because it is beginning to support ethical stem cell research? No! I don’t care if the CIRM swore off ESCR for good. The state is sinking beneath the red ink waves. School funds are being cut, the UC system is a mess, health care is shriveling, and our state parks are only going to be open on weekends. The Bay Bridge is falling–literally–apart and other infrastructure is in trouble. We have debt past the horizon with no relief ship in sight. If the CIRM really wanted to help California, it would close up shop.”

On an industry blog, In Vivo, Alex Lash focused on Novocell, which will receive CIRM's first-ever loan for its research.

The Toronto Sun carried a small story. It appears that coverage was light in Canada and the United Kingdom, probably because the size of the grants involved there was relatively modest.

Here are our reports yesterday on the NY Times and Nature coverage.

NY Times: CIRM Moves Away From hESC

The New York Times today reported that the California stem cell agency has made a “tacit acknowledgment that the promise of human embryonic stem cells is still far in the future.”

Reporter Andrew Pollack wrote that only 4 of the 14 disease team projects approved by CIRM today involve embryonic stem cells. He said,

"The others will use so-called adult stem cells or conventional drugs intended to kill cancer stem cells, which are thought to give rise to tumors."

Pollack continued,

“The grants thus represent a departure from the program’s original mission. California voters approved the 10-year, $3 billion effort in 2004 largely to get around restrictions on embryonic stem cell research imposed by the administration of President George W. Bush.”

Pollack asked CIRM Chairman Robert Klein about the emphasis on non-hESC projects in the disease team round at news conference today. Klein said that the commitment to voters was to “pursue the very best cell type for each disease.”

Nature magazine also pointed out today that the disease team round involved few grants using hESC.

A Peek at News Coverage of CIRM's $230 Million Disease Team Round

California's stem cell research effort today climbed over the $1 billion mark with its whopping disease team round. The awards began generating news coverage internationally this afternoon, and more stories will surface later today and tomorrow.

Erika Check Hayden filed a report on Nature magazine's breaking news blog. She said CIRM regards the round as the “crown jewel of its portfolio.” She said that some of the grants will go “for therapies that, in some cases, are unlike any ever before approved by the FDA.”

Hayden wrote,

“Only a handful will employ human embryonic stem cells, despite the fact that most of the fanfare surrounding the passage of Proposition 71, the ballot measure that created CIRM, concerned the fact that CIRM would fill the gap left by a lack of federal funding for work on these cells. But Bob Klein, architect of Proposition 71 and chair of CIRM's governing board, said, 'Our commitment to the voters was that we would pursue the very best cell type for each disease based on the scientific and clinical evidence.'"

Rob Waters of Bloomberg emphasized the business aspects and had a separate piece on Sangamo Biosciences of Richmond, Ca., a publicly traded company that shared in a $14.6 million award with City of Hope in Duarte, Ca.

Oddly, the largest newspaper in California, the Los Angeles Times, had not carried a word as of this writing on the roughly $80 million in grants to institutions in the Los Angeles area.

The New York Times may well have story late today or tomorrow. Its Los Angeles-based reporter, Andy Pollack, could be seen on the Webcast of the news conference, asking a question about the slim use of human embryonic stem cells in the disease team grants.

Here are links to other stories:
Thomas Kupper of San Diego Union-Tribune
San Diego News Network
Steven Brown of the San Francisco Business Times
DelMar Times

CIRM News Release: More than $250 Million in Disease Team Round, Including International Partners

The California stem cell agency has posted its press release on the largest research round in its history.

The release notes that, with funding from international partners, the total comes to more than $250 million. The release also contains the identities of all the winning researchers and their institutions.

CIRM News Conference Link

Here is a link to the live news conference on CIRM's $230 million disease team program.

California Stem Cell Agency Approves $230 Million Aimed at Clinical Trials

The California stem cell agency today formally awarded $230 million to 14 teams of scientists in the largest and most ambitious round of research grants in CIRM history.

Already the world's largest source of funding for human embryonic stem cell research, the $3 billion agency said the grants and loans would lead to the beginning stage of clinical trials in four years.

The disease team round also marks the first foray into what is expected to be a risky, $500 million loan program for the biotech industry. The round is additionally a critical step in building support for continued funding of the agency, which will lose the ability to finance itself sometime in the next decade.

The goal of the disease team effort is to generate filings to begin a clinical trial within four years or less. That would presumably lead to creation of therapies that could alleviate the suffering of thousands. CIRM could also use the results to ask the legislature or the people of California, by ballot measure, for additional funding.

The disease team round is the first major effort involving international partners, Canada and the United Kingdom. Organizations in those countries are collaborating with California partners and adding many more millions to the research largess.

All of the grants in tier one were approved, although application 1471 had conditions attached because of a change in the employment of a co-PI in the United Kingdom.

Concerns About Size of Disease Team Round

Some CIRM directors seem to be concerned about the overall size of the disease team package and the original budget of $210 million.

There may well be an effort to trim the overall size, which would mean that some grants in tier one are removed. Normally all grants in tier win ultimate approval from directors, but they have the ability to do whatever they want.

City of Hope Wins Initial Appeal

Directors of the California stem cell agency this morning gave a positive nod to an attempt to win approval of an application from the City of Hope in the agency's disease team round.

The board approved, on a unanimous vote, a motion to move the application into the first tier of grants expected to be approved later today.

The grant was proposed by Karen Aboody of City of Hope in Duarte, Ca., to study development of treatments for brain tumors.

Aboody filed an extraordinary petition to overturn a negative decision by CIRM reviewers, who gave the application a score of 43 on a scale of 100.

CIRM Vice Chairman Duane Roth said he would support the grant because information in the review was incorrect. Another director concurred with Roth's comments.

The size of the grant was not immediately available.

(Editor's note: The vote tally is based on votes that were audible on the board Web audiocast. The ultimate figure may vary slightly.)

City of Hope Grant Being Discussed

The CIRM board is now discussing an appeal on a grant proposal by Karen Aboody of the City of Hope.

CIRM Directors Nix Buck Appeal

Directors of the California stem cell agency turned back an attempt to win approval of a $17 million application from the Buck Institute on a stem cell research proposal involving Parkinsons disease.

The board rejected, on a 6-11 vote with one abstention, a motion to move the application into the first tier of grants expected to be approved later today.

The grant was proposed by Xianmin Zeng of Buck and co-PI Mahendra Rao, vice president of Invitrogen and former head of the stem cell group at National Institute of Aging.

Scientific reviewers gave the application a score of 53 and did not recommend it for funding.

Zeng filed an “extraordinary petition” and personally appeared before the board this morning. She said the criticisms by reviewers were minor or technical and have already been addressed or are being addressed.

The motion to move ahead on the grant was offered by CIRM Director Joan Samuelson, who has Parkinsons.

(Editor's note: The vote tally is based on votes that were audible on the board Web audiocast. The ultimate figure may vary slightly.)

Buck Institute Application Being Discussed

The board of the California stem cell agency has resumed its discussion of disease team grants and loans. Currently it is considering an effort by Xianmin Zeng of the Buck Institute for Age Research to overturn a negative decision on her application by science reviewers.

Looking at CIRM Grant Appeals Issues

Here are links to documents relating to the California stem cell agency and complaints about fairness in its grant review process.

Text of CIRM policy on appeals via "extraordinary petition."

An October 2008 examination of transparency and conflict of interest issues

Consumer Watchdog Identifies Businesses Rejected for CIRM Grants

First ever successful conflict appeal, December 2008

CIRM's August 2008 proposal for a reconsideration procedure

Transcript of August 2008 CIRM Meeting

Proposal by CIRM Director Jeff Sheehy on grant appeals, July 2008.

First mainstream media article ( July 2008) about complaints about fairness in CIRM grant-making

Cascade LifeSciences Seeks Reconsideration

Text of Cascade's Reconsideration Letter

CIRM Response to Cascade

Transcript of June 2008 CIRM Meeting Involving Cascade

Transcript of the January 2008 CIRM directors meeting, which heard the first public appeal of a scientific review. Search on the term "luben," which is the misspelling of the name of Bertram Lubin, president of Childrens Hospital Oakland Research Institute, who appeared before the directors seeking reconsideration.

Nature magazine article April 30, 2008, in which Lubin comments on CIRM

California Stem Cell Report account of part of the January meeting involving the Lubin appeal.

Weissman's $20 Million Proposal Dodges Rejection

A $20 million grant application from reknown scientist Irv Weissman of Stanford tonight avoided disaster as CIRM directors overturned a decision by scientific reviewers to reject the proposal.

The application was moved, 14-2 vote with two directors abstaining, into the top tier of disease team grants that are headed for approval by the directors tomorrow morning.

Another $20 million application from Stanford's Gary Steinberg was also moved into the first tier on a separate vote, which was either 13-3 or 12-4. One director's vote was inaudible on the Web audiocast.

The Steinberg and Weissman applications bring to 13 the number of grants in the first tier for a total of $207 million. That is just under the $210 million budgeted for the disease team effort, the largest research grant round in CIRM history.

Both applications were the subject of an “extraordinary petition,” along with four other applications. One of those efforts was not successful tonight. No director made a motion to move a $12 million proposal by Aileen Anderson of UC Irvine to the first tier.

(Weissman's petition can be found here, Steinberg's here, Anderson's here. The other petitions are from Judith Shizuru of Stanford(here), Karen S. Aboody of the City of Hope(here) in Duarte, Ca., and Xianmin Zeng of the Buck Institute(here) in Novato, a town north of of San Francisco.)

The directors have recessed until tomorrow morning. They did not take up the other petitions tonight as they worked their way through the grants that CIRM's grant reviewers said were not worthy of funding. Weissman's application received a scientific score of 65, below the cutoff line of 70. Steinberg's and Anderson's scores were not available.

Regarding the Weissman application, CIRM Chairman Robert Klein said some of the reviewers may have been less than objective because they do not believe that cancer stem cells exist. The subject is a matter of some scientific dispute. CIRM President Alan Trounson disagreed with Klein on the possibility of prejudice but said that the grant could be worthy of funding.

Director Ted Love, who served as CIRM's chief scientific officer during the review, said the board could feel comfortable funding the grant or not. He said he did not think it would be “unwise” to fund the application.

Weissman's name was not mentioned during the discussion, but some commented about respect for the principal investigator. The United Kingdom is also involved in the grant, providing an additional $4.3 million, according to Trounson.

The board is scheduled to resume deliberations at 8:30 a.m. PDT tomorrow in Los Angeles. CIRM has scheduled an 11 a.m. news conference to formally announce the grant winners. The meeting will be audiocast on the Web. Directions for listening are on the agenda.

Correction

The “public appeal” item on Oct. 27, 2009, incorrectly said that extraordinary petitions filed by six grant applicants were not available on the CIRM Web site. The petitions were not noted on the CIRM board agenda but could be found three layers down on six of the 20 summaries of the grants rejected by reviewers.

Weissman's Grant and Appeal Now Being Discussed

Currently being discussed by the CIRM board is a rejected grant (1485) by noted Stanford scientist Irv Weissman.

Advisory

The meeting of the California stem cell agency board has resumed with much improved clarity. Up for discussion are the $167 million in disease team grants and loans.

Six Rejected Grant Applicants Make Public Appeal to CIRM Board

Six research teams that lost out in CIRM's closed door reviews of their applications for up to $20 million dollars are now seeking to overturn the decisions.

The rejected applicants include three from Stanford(Irv Weissman, Judith Shizuru and Gary Steinberg), one from the City of Hope (Karen S. Aboody) in Duarte, Ca., one from UC Irvine(Aileen Anderson) and one from the Buck Institute(Xianmin Zeng) in Novato, a town north of of San Francisco.

Their “extraordinary petitions” are not yet available on the board's agenda, but their existence was confirmed by John M. Simpson, stem cell project director for Consumer Watchdog of Santa Monica, Ca. Simpson was attending the meeting in Los Angeles and supplied the applicants' identities from CIRM documents available at the session.

We queried him about the petitions after hearing a partial comment on the Web audiocast of the meeting, which has been largely muddled at our location in Mazatlan.

Simpson also said that one key board member told him that the six petitions raise “substantive scientific issues.” The efforts to overturn the negative results raise some other interesting issues because CIRM budgeted $210 million for the disease team grant round while reviewers only approved $167 million.

The extraordinary petition process is relatively new at CIRM. It was created in September 2008 in response to public appearances by rejected applicants at CIRM board meetings. None have been successful using that method and none have been successful in using the extraordinary petition process.

A number of board members have been clearly uncomfortable with the public presentations by unhappy applicants. They have also been loath to overturn the decisions of the Grants Working Group and the scientists who are members of it.

The issue bubbled up in June 2008, leading to an extended public board discussion of the appeal or reconsideration process. CIRM allows "appeals" only in the case of conflicts of interest on the part of reviewers. However, reviewers do not have to publicly disclose their economic or professional interests.

The extraordinary petition process requires the applicant to file a request for reconsideration five days prior to a directors meeting. CIRM's president will then evaluate it and make a finding on whether it has merit.

Here is an account of how the petition process worked last January.

(Editor's note: An earlier version of this item incorrectly said the petitions were not available on the CIRM Web site.)

CIRM Board Recesses for Confidential Grant Review

Directors of the California stem cell agency have gone into executive session to discuss confidential information related to applications for $167 million grants and loans in the agency's disease team round.

The CIRM board moved into closed door discussions tonight shortly after the CIRM staff presented a brief overview of the round. It is not clear when the board will return to open session.

The agency has called a news conference for 11 a.m. PDT tomorrow to formally announce the awards and publicly identify the winners.

Advisory

If you are having difficulty hearing the audiocast of the meeting of the CIRM board, so are we. We are told that they are working on improving the quality.

Trounson's Report to Directors Posted by CIRM

The California stem cell agency has posted the slides that its president, Alan Trounson, will use to brief directors this afternoon on the state of CIRM.

They include his assessment and summary of recent stem cell research worldwide, his priorities and upcoming rounds for new grants.

Also on tap is a briefing by Geoff Lomax, senior officer for medical and ethical standards, on CIRM's Compliance Program. It is a presentation that CIRM grant recipients and their allied institutions should pay close attention to.

CIRM is expected to have about $1 billion in grants in place by the end of this week. Close monitoring of that cash and the performance of the recipient institutions and scientists is critical to CIRM's credibility.

Brighter Financial Outlook for CIRM

The California stem cell agency began 2009 with an alarming and surprising report about its financial condition. Today the picture is much brighter.

John Robson, vice president for CIRM operations, is scheduled to brief the agency's directors this afternoon about the current state of CIRM finances.

His best news will be about the $118 million CIRM received from the recent California bond sale. The cash will provide funding up to about June of 2011. Unless something truly catastrophic happens, California is likely to sell billions in more bonds between now and then, some of which will keep CIRM research funds flowing.

In response to a query, Don Gibbons, CIRM's chief communications officer, also told us a few days ago that $14.8 million of previous CIRM(state) debt has been reclassified as tax-exempt bonds. That means lower interest costs for the state.

You can find Robson's Power Point presentation (slide 36) here.

Coverage Advisory

Assuming all goes with our Internet connection here in Mazatlan, we will bring you coverage this afternoon and evening of today's meeting of the board of directors of the California Institute for Regenerative Medicine, otherwise known as the the California stem cell agency. The main order of business tonight is discussion and possible action on $167 million in disease team research. The meeting begins 4:30 p.m. PDT.

How the Lucky 11 Made Their Way: A $200 Million Tale

Seventy-three pilgrims started out on California's disease team trail last March, looking to share $210 million. Only 11 have finished, unless the men and women who control $3 billion decide differently.

The initial number of stem cell argonauts was substantially less than predicted by Alan Trounson, president of the California stem cell agency, which is financed by $3 billion borrowed by the state.

Last January, Trounson told CIRM directors that he anticipated more than 100 applicants. The prizes were alluring: up to $20 million each.

But only 73 teams filed “pre-applications,” Trounson said in April. Thirty-two of those were invited to submit full applications following CIRM's new grant triage process, which involved scientific specialists from outside California and CIRM staff.

In June, Trounson reported to directors that eight of the 32 invitees had commercial partners or were led by a business. Nine involved international collaborations, down from 18 in preliminary process. (CIRM reported scores on only 31 applications. Presumably one of the 32 did not apply or failed to qualify for some other reason.)

CIRM is ballyhooing the international aspects of the disease team round, whose original California budget was $210 million with up to 12 successful teams. The 11 likely winners account for only $167 million. But funds from the United Kingdom and Canadian teams will boost the combined total to $200 million, according to CIRM.

The results of the disease team round could be an important indicator of CIRM-industry relations. Some businesses have expressed dismay in the past with CIRM after their applications were denied, sometimes appearing at board meetings to vent their concerns. They are generally rebuffed by directors.

Trounson and others, however, have been talking for months about improving ties with the biotech. The updated strategic plan(also up for a final vote this week) calls for closer links. And Trounson has created a new position (yet to be filled), vice president for research and development, to help encourage more amicable relations. He is hoping to attract a candidate with industry experience.

CIRM reviewers rejected 20 disease team applications. Based on our latest look at the agenda, none have sought to overturn the result via the agency's “extraordinary petition” process. But those appeal letters often show up late publicly. Any applicant can also appear before the board and ask for reconsideration of reviewers' decisions for any reason. Few have.

Only four applications received scientific scores above 80. The highest was 90. The other seven ranged in the 70s. Rejected applicants fell below that line, although their scores are not released publicly. The general ranking of the unsuccessful applicants can be determined by examining the listing of the grants. CIRM has made a practice of ordering all the application summaries by their score. For example, application 1480 is the first to fall below the 70 cutoff. If CIRM follows past practice, 1480 has a much higher score than the last application, 1449, listed on the summary.

Sometimes CIRM directors have discussed whether the difference between a score of 70 and 68 has any significance. Those discussions usually come up when they are considering moving an application out of the “not recommended” category. Given that there is more cash available, some directors may move to approve an application just below the cutoff line.

Directors, with the exception of those on the grant review group, do not have access to the full application. Nor are the names of the individuals or institutions disclosed to directors, although considerable information is contained in the review summaries that provide clues to applicants' identities.

Directors also are barred from voting or even discussing applications in which they have a conflict of interest. Usually directors vote on the top-tier grants as a block, officially recording their votes with this language, “Yes, except for those on which I have a conflict.”

Since many of the 29 directors come from institutions that often have applications before CIRM, the votes of the “non-conflicted” board members (mainly patient advocate representatives) are very important in order to complete legal action on the applications.

CIRM has a supermajority quorum requirement – 65 percent – written into state law by Prop. 71, which created the stem cell agency. The quorum is based on those eligible to vote. While quorum and attendance problems have hampered the board with some frequency in the past, we suspect that will not be the case this week. CIRM Chairman Robert Klein has more than once emphasized the importance of the disease team round in terms of producing results that will help CIRM find funding to continue its work beyond the 10 years it can issue bonds.