Tracking the Evolution of the Stem Cell Genomics Applicants

The plan to create one or two stem cell genomics centers in California at a cost of $40 million began in 2012. Since then there have been some changes, some of which resulted from the failure of reviewers to recommend any proposals in 2013.

Last week, the California Stem Cell Report (CSCR) asked the California stem cell agency(CIRM), which is scheduled to make a decision today on an at least one application, about several of the changes. Here are the texts of the questions and answers from the agency.

CSCR: Has the cast of applicants changed since the initial review in early 2013? Have some dropped out or been added? Have the applications been recast significantly for the most recent review?

CIRM: Applicants to the first round of review were eligible to participate in the second round.  Although review criteria remained the same as those stated in the RFA, applicants were allowed to change proposal components, establish new collaborations and/or combine efforts.  

CSCR: How many letters of intent (LOI) were received with a breakdown on the number from academic and business enterprises?  How many applications were received, also with a breakdown on academic and business?

CIRM: For the first round, there were 9 LOI's; 7 of these submitted applications.  No LOI was required for the second round.  All first round applicants participated in the second round of competition, but several have combined efforts, so there were 5 applications in the second round.  Three of these applications were collaborative proposals combining both for-profit and not-for-profit organizations, while the other two were from not-for-profit institutions.

Upcoming: Live and Complete Coverage of Tomorrow's $80 Million Stem Cell Meeting

Check in tomorrow on the California Stem Cell Report for gavel-to-gavel coverage of the meeting of the governing board of the $3 billion California stem cell agency. As much as $80 million is at stake, including a $33 million plan by a Stanford consortium to create a world-leading stem cell genomics center.

The meeting is scheduled to begin at 9 a.m. PST. Coverage will begin at that time with stories filed as developments warrant.

For those who want to attend the event, it will be in Berkeley. Teleconference locations are in La Jolla and Los Angeles. The meeting will be audiocast on the Internet with a WebEx transmission of documents that are displayed for the board. Full instructions are on the meeting agenda along with the addresses of the teleconference locations and the actual meeting.

Goldberg Departs from California Stem Cell Board; Panetta and Miller Join

The California stem cell agency is losing another of the original members of its governing board but two new ones with markedly different backgrounds will be joining the 29-member panel tomorrow.

Departing is Michael Goldberg, a venture capitalist from the San Francisco Bay area. He has served as head of the board's finance subcommittee. Along with Marcy Feit, another longtime board member, he has cleaned up the accounting

Michael Goldberg
Mobihealth News photo

mess that once made the $3 billion agency's operational budget nearly incomprehensible.

In response to a question from the California Stem Cell Report, Goldberg said,

"John Thomas's leadership (as agency board chairman) has long been firmly established and it is now time for me to step aside to allow for a new appointee to contribute to taking CIRM to the next level.

"I will be forever indebted to have had the privilege to serve my fellow Californians as a member of the ICOC(the agency governing board). As a patient advocate and member of industry I am extraordinarily proud of what CIRM has accomplished to date and enormously enthusiastic about our future prospects for improving patient care and bettering the health care economics of our state."

Joe Panetta
Biocom photo

Joining the board in Berkeley tomorrow are expected to be Joe Panetta, head of Biocom, and Hollywood actress and writer Lauren Miller. Both were appointed by California Gov. Jerry Brown, who sometimes is noted for his unusual choices in personnel.

Panetta, however, does not fit that category. He is a longtime figure in the biotech community in California. He has been head of Biocom, the life sciences industry association in the San Diego area, since 1999. He fills the vacancy left by the death of Duane Roth, who was also came from the San Diego business community.

Lauren Miller
Ivan Nikolov/WENN photo

Brown's other appointment, Lauren Miller, comes from a far different perspective. She wrote the script for the movie "For a Good Time, Call..." Last spring, she and her husband, actor and director Seth Rogen, staged a fundraiser last year called “Hilarity for Charity” on behalf of Alzheimer's, generating more than $500,000 in donations.

CIRM quoted Miller in a press release as saying,

“To have the opportunity to learn about, and support the research for so many important diseases is such a great honor and responsibility and I look forward to starting.”

The agency also said,

“Miller’s commitment to raising awareness about Alzheimer’s comes from her family’s battle against the disease. Her grandfather died of Alzheimer’s and her mother was diagnosed with it when she was just 55 years old.”

Miller replaces Leeza Gibbons, another celebrity who is a patient advocate for Alzheimer's.

$21 Million Likely for California's Basic Stem Cell Research

Directors of the California stem cell agency tomorrow are expected to approve at least $21 million for basic research into “significant, unresolved issues in human stem cell biology.”

The round was originally slated for $40 million but grant reviewers decided to fund only 20 applications out of 62. The round began with 341 scientists filing pre-applications.

(Here is a link to reviewers' summaries and rankings as well as a link to the CIRM staff's Power Pointpresentation.)

CIRM President Alan Trounson and his staff recommended approval of five additional applications totaling$4.8 million. The rationale in their recommendations could be considered fulsome compared to what Trounson offered on the $40 million genomics round also to be considered tomorrow.

Five additional researchers filed letters with the CIRM governing board seeking its approval. Those letters can be found on the agenda for tomorrow's meeting. Seven researchers filed formal appeals with the CIRM, which are now dealt with behind closed doors by the agency's staff.

The 20 applicants given the nod by reviewers were placed in a tier one category that is virtually certain to be approved by the board with no debate. Others were ranked in a wobbler category called tier two, meaning it could go either way for the scientists. The remainder fell into tier three – not recommended for funding by reviewers.

The board is increasingly turning to proposals that will turn more advanced research into clinical treatments. If directors do not go for spending the entire $40 million budgeted, they would save money that could be used for clinical trials. However, aside from the general arguments for doing basic research, those grants provide large sums to recipient institutions to pay for their overhead. And many of the agency's board members come from institutions that could benefit from payments for those overhead costs. Those board members will not be allowed to vote on applications involving their institutions.

(Editor's note: The number of researchers filing formal appeals was not contained in an earlier version of this article.)

California's Stem Cell CEO Search: Dangling a 16-page Lure

The California stem cell agency yesterday posted what could be called a recruiting brochure for the effort to hire a new president to replace Alan Trounson.

The document, which was prepared by the search firm Korn Ferry, is couched in language designed to stimulate interest in those seeking a challenge and opportunity.

• “Few technologies have captured the imagination of the public quite like human stem cells,” the brochure begins.
• “Transformative public funding,” it says at one point.
• “One of the most influential agencies in the universe of stem cell research,” it says at another.

The 16-page brochure deals directly with less pleasant aspects of the job such as the likelihood that the agency could wind up in hospice care in three years when the money for new grants runs out.

It is also surprisingly forthright about the longstanding and controversial problem of the dual executive arrangement decreed by law. It may be the first time that the agency has so directly admitted publicly and formally that the overlapping responsibilities of the president and chairman have caused serious difficulties. 

The document says,

“This unique partnership has amply demonstrated its value when the president and chair have worked well together, but the organization has suffered when this has not been the case. An ability to adapt to this model of governance and management will be a critical attribute for the next president.”

The CIRM/Korn Ferry brochure is explicit about the direction of the agency towards pushing therapies into the marketplace and clinic. That is significant because of continuing pressures to well fund basic research, which means less money for efforts that are closer to clinical use. The document says,

"With the remaining resources of the state’s commitment, it is CIRM’s intention to focus its funding decisions increasingly on a host of projects with particular clinical promise, bringing the science it has strategically cultivated to the fruition of human therapy.  Both the governing board and the staff of CIRM are committed to this pivot in organizational priorities, driven to fulfill the dream of the people of the State...."

It is unclear when a new president will be on the scene. There is talk about a hire being made by April or May, but having the new person actually in the office five or more days a week could be a different matter. Trounson said last November he would stay on for awhile. But his family remains in Australia, where he is seeking to return.

The directors' Presidential Search Subcommittee meets tonight in Berkeley to discuss the brochure, which the agency labels a "candidate position statement." Korn Ferry has a $160,000 contract with the agency. The agency has previously used search firms in its presidential recruitment. None of them have come up with the person that was ultimately hired.  

Teleconference locations where the public can comment are available in Costa Mesa, La Jolla and San Francisco. Specific addresses can be found on the agenda.

(Editor's note: The three sentences on the size of the Korn Ferry contract and the success of previous search firms were not contained in an earlier version of this story.)

Inside Stem Cell HQ: A Look at the Tiny Staff

The staff of the $3 billion California stem cell agency is small – very small.

Cynthia Schaffer
CIRM photo

At one point point midway in its history, they probably probably amounted no more than the number of workers at your average Burger King. Today the staff even outnumbers the 29 persons who sit on its governing board. At one point in years past, it did not.

The staff has had its share of turnovers, but there is something certainly different about its esprit compared to most state agencies.

Yesterday, one of its longtime staffers, Cynthia Schaffer, wrote a little about the nuts-and-bolts operations and the nearly 60 persons who work at stem cell HQ at 210 King Street, across the street from the the San Francisco Giants baseball park. Her item appeared on the agency's blog. Check it out.

California's $40 Million Genomics Awards: Stem Cell Agency Defends its Review Practices

The California stem cell agency today defended itself against charges that scoring on grant applications was manipulated in its $40 million genomics grant round to the benefit of a consortium headed by Stanford University researchers.

In response to a query from the California Stem Cell Report, the agency said its practices were “consistent with many previous reviews.” The agency also said that its RFA specifically allowed the adjustments that were made by the agency.

In a letter to the agency's board, Pui-Yan Kwok, leader of a proposal offered by UC San Francisco and UC Berkeley, had challenged the scoring on a $33 million proposal from the Stanford consortium. If the board goes along with reviewers and CIRM President Alan Trounson, Stanford's application will be the only one approved on Wednesday at the board meeting in Berkeley.

Trounson has recommended to the board that it not fund three other applications that were approved for funding by reviewers. He offered no rationale for his recommendation. The board, however, has almost never rejected positive recommendations from its reviewers on hundreds of applications during the last nine years. 

Here is the full text of the agency's response as delivered by Kevin McCormack, senior director of public communications.

“I think the UCSF researcher was mistaken when he said: 'We were surprised to see that the genomic center scores of the top two applications were based on the reviewers removing from consideration the poorest performing center-initiated projects.  The fact that the reviewers could propose removal of individual center-initiated projects was never mentioned in the RFA.'  

“Because the RFA specifically states: 'The GWG will make funding recommendations to the ICOC concerning which Centers and which Center-initiated projects (within a particular award) to fund. The GWG may also make specific recommendations concerning the budget for each proposed award. The ICOC will make final funding decisions.' 

“This practice is consistent with many previous reviews in which the GWG recommended removal of distinct Specific Aims or proposed activities. 

“Also in the letter, the UCSF researcher says: 'Even more appalling is that this was applied only to the two applications (that) ended up with the highest scores.  The end result is that two centers' scores were artificially inflated to 88 and 82, respectively.  Despite this uneven application of the review process, two other applications received Tier 1 (recommended for funding) scores.  This appearance of preferential treatment makes the process suspect.' 

“However, reviewers were instructed that they could recommend removal of specific Center Initiated Projects (provided that at least 2 remain) if they felt this action would strengthen the overall proposal. This option was available for every application considered.

“For proposals where there was no recommendation to remove Center Initiated Projects, reviewers did not believe that the overall score would be significantly increased by such removal.”

California's $40 Million Genomics Round and Conflicts of Interest

Concerns about conflicts of interest have dogged the California stem cell agency since its earliest days, and they continue into this week's $40 million genomics round.

They were first raised in the ballot campaign of 2004 when California voters were asked to create the $3 billion research program. And they were of sufficient concern eight years later that the highly regarded Institute of Medicine said in a $700,000 study of the agency that it should act to minimize potential damage.

The institute said in its 2012 report, commissioned by the agency itself,

“Far too many board mem­bers represent organizations that receive CIRM funding or benefit from that funding. These com­peting personal and professional interests com­promise the perceived independence of the ICOC(the governing board), introduce potential bias into the board’s decision making, and threaten to undermine confidence in the board.

The latest concerns arise, however, not in connection with the governing board. They have surfaced in connection with the closed-door grant review process and subsequent recommendations by CIRM President Alan Trounson in a plan to create one or two stem cell genomic centers. Trounson advised the board to approve $33 million for a single proposal led by researchers at Stanford University.

Two applicants in the genomics round, UC San Francisco and the Scripps Research Institute, have complained in letters to the agency's board about unfairness, apparent preferential treatment and manipulation of scores on the Stanford application, among other things. The applicants do not specifically allege that conflicts of interest exist in the genomics round. Nor do they identify a motive behind what one applicant said were “appalling” actions.

But the round has a checkered history that does, in fact, involve actual conflicts of interest.  connected to Trounson, CIRM grant reviewer Lee Hood of Seattle and Stanford stem cell researcher Irv Weissman. Some concerns were also voiced privately by researchers as far back as 2012 when renown genomics researcher Craig Venter, now part of the Stanford application in this week's round, pitched the CIRM board on stem cell genomics. Only an hour or two following his presentation, the board, with virtually no discussion, approved the concept behind the genomics round along with a $40 million budget. Approval came on a voice vote with no dissent.

Applications came in about eight months later for what CIRM said would be one or two awards that would propel California into a world class leadership position in the new field. Trounson recruited Hood, who is another internationally recognized genomics expert, to serve as a grant reviewer. As reported by the California Stem Cell Report in May 2013, one reviewer in the first of two genomics grant review sessions raised a question about Hood's participation. Hood subsequently acknowledged that he failed to disclose his relationship with Weissman, who was involved in what was then a $24 million application from Stanford. The men are friends and partners on a ranch in Montana. CIRM staff had failed to detect the conflict.

Prior to the genomics round Trounson had acknowledged he had a conflict-of-interest in connection with another Weissman-related proposal. In 2012 in a round not related to genomics, Trounson, who has visited the Hood-Weissman ranch as Weissman's guest, recused himself from the board's public discussions of applications from StemCells, Inc., a company founded by Weissman.

Under CIRM's procedures, Trounson does not vote on applications during the review process. But beginning last year the board gave him and his staff new authority to make recommendations on applications after they were acted on by reviewers.

Following the Hood violation, the proposals were sent back to scientists for resubmission. By the time Stanford's proposal was approved by reviewers and came to Trounson for his consideration, Stanford had removed Weissman's name. According to a letter from Stanford, the associate director of Weissman's stem cell institute at Stanford, Michael Clarke, is now a “collaborator” on the project.

In documents on the CIRM Web site, Trounson also told the board, with no explanation, that it should not approve any cash for the applications for two competing proposals from UC San Francisco and Scripps and a third believed to be from UCLA. All three were recommended for funding by CIRM's blue-ribbon reviewers, all of whom are from out of state. Normally the board has rubber-stamped hundreds of such recommendations by reviewers. It would be a radical change for the board to turn its back on reviewers' opinions on three major proposals.

The California Stem Cell Report asked the agency last week whether all staff members, including Trounson, who were involved in the recommendations were screened for “personal, professional and financial conflicts.”

Kevin McCormack, senior director of communications for the agency, replied,

“Dr. Trounson’s participation in the staff recommendations regarding the stem cell genomics award was consistent with state law and CIRM policies.”

McCormack also said that the CIRM legal staff “ensured, as they always do, that employees with conflicts did not participate in the review of applications in which they had a conflict.”

Our take:

It is not unreasonable to consider that Clarke, the associate director of Weissman's institute, is a surrogate for Weissman in the Stanford proposal and presents at the very least the appearance of a conflict of interest for Trounson

The situation does not well serve the agency, which is in the process of trying to develop funding for its operations after 2017, when money for new grants will run out. Prospective investors, be they private or public, would expect the agency to act in such a manner that would avoid the sort of flap that has arisen in the genomics round. That is not to mention the need to maintain the confidence of the public and the stem cell community. 

California's Stem Cell Genomics Round Receives National News Attention

The Associated Press, a worldwide news service, has picked up and distributed a rewritten version of Sunday's story in The Sacramento Bee about the California stem cell agency's $40 million genomics round.

The AP article has appeared on a wide array of online news sites served by the AP including the San Francisco Chronicle, Newsdaily, Modern Healthcare, California Healthline, the Washington Times, a host of television station news sites and many more.

The California stem cell agency is not often the subject of national media attention but stem cells and genomics can combine to generate media interest. 

The AP story does not go beyond the story that appeared in The Bee (written by yours truly) and does not include charges of unfairness and score manipulation reported Saturday on the California Stem Cell Report. The story in The Bee had an early deadline and the information on the allegations surfaced too late to include in The Bee article.

The stem cell agency says it is preparing a response to the charges.  

The AP is a member-based business. Under the usual arrangements with its members, such as The Bee, it is entitled to pick up and redistribute stories that are published by its members. 

Alan Trounson's Opaque Messages, Genomics and $40 Million

Cryptic is probably a good word for the messages delivered last week by the president of the California stem cell agency, Alan Trounson, in his recommendations in the agency's $40 million genomics round. Odd might be another.

Some might say Trounson is ill-serving both the board that hired him and California taxpayers.

Alan Trounson
UCSD photo

In a document on the CIRM Web site, Trounson, who is a noted researcher from Australia, says the 29-member governing board of the agency should give $33 million to a Stanford-led consortium to create a stem cell genomics center. That coincides with the opinions of the agency's blue-ribbon scientific reviewers.

Trounson's rationale, however, is no more than a 23-word phrase among four paragraphs that are little more than a generic description of a stem cell genomic center. The Stanford proposal, he said, “will fulfill all of the aims of the RFA and provide an excellent, responsive and comprehensive genomics resource for California stem cell researchers.”

Trounson's recommendations on three competing proposals(here, here and here), all of which were also approved for funding by reviewers, are even more opaque. He simply says,

“CIRM Staff Recommendation: Do not fund”

Trounson's name is missing from the CIRM documents nixing the three proposals. But Trounson calls the shots at the agency and signs off on any advice to his board.

His recommendations would be a dramatic and major change in how the board treats the positive decisions of its reviewers. Over its nine-year history, the board has almost never overridden positive findings by reviewers. Invariably they are rubber-stamped with no discussion at public board meetings.

CIRM's directors are loathe to substitute their judgment for reviewers for a variety of reasons. One is that the board members do not see the actual applications – only the same review summaries provided to the public. The identities of the applicants are also withheld from directors prior to their vote on applications. Board members have repeatedly said they do not have sufficient information to reverse reviewer decisions. They also do not want to offend reviewers. The board fears that they might abandon the task of reviewing applications for the agency if their decisions are not supported by the board.

Trounson, who announced last fall he is leaving the stem cell agency, offered no explanation for his move to turn the longstanding board practice on its head. Nor did he discuss why the genomics round should be limited to one award when the RFA stipulated one or two.

He did not discuss the policy implications of the state of California giving a $33 million leg-up to a single consortium in a hot, fast-growing scientific and business arena. He did not comment on the possibility that this consortium would be less than welcoming to rival researchers. 

He did not discuss whether creation of this consortium was akin to creating an organization like WARF that sets the rules and controls the playing field on the use of important human embryonic stem cell lines, much to the displeasure of many scientists, including Trounson himself. Nor did he even publicly disclose the amount of money that was requested by researchers whose applications he would deny.

There may be good reasons for Trounson's position. But he owes the board and the public more than a cryptic decree sent forth from his post at 210 King Street in San Francisco.  Especially in light of the charges of unfairness, score manipulation and more leveled last week by rival researchers in the round.

Sacramento Bee: California Stem Cell Agency Betting Big on Genomics

The Sacramento Bee today published an article by yours truly on this week's $40 million genomics round and its significance.

It was a freelance piece that was aimed at a general audience. The article also had an early deadline – last Wednesday. After it was submitted, additional developments popped up, some of which made it into the article. However, the piece was actually in print by the time of the most recent developments related to researchers' serious complaints about the genomics review process. So those elements did not make it into the story .

Here is the article. See here for how it looked on The Bee's Web site.

California’s stem cell agency poised to bet big on genomics research

By David Jensen
Special to The Bee

The state of California is preparing to make a bet of up to $40 million on a fast-moving field that promises to revolutionize medicine and ultimately lead to personalized stem cell treatments that can be tailored for a patient’s genetic makeup.

Directors of the California stem cell agency are meeting in Berkeley on Wednesday to create one or two stem cell genomic centers that they predict will make the state a world leader in the new field. Scientists and businesses from biotech centers in the Bay Area, San Diego and elsewhere are competing for the money.

The move into genomics comes as the $3 billion agency struggles to fulfill the promises of the ballot initiative campaign of 2004, when voters approved its creation with a total of $6 billion in state spending, including the interest on bonds sold to finance the endeavor. So far, no therapies or cures have emerged from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. It will run out of cash for new awards in less than three years and needs some high-profile results to raise more money.

Scientists and biotech businesses say they hope that genomics, the study of genes and their relationships, can lead to a catalog of disease genes and pave the way for new therapies that are tailored to individual needs. Linking stem cell treatments, which also promise extraordinary results, could provide even more effective treatments. UC Davis stem cell researcher and blogger Paul Knoepfler describes the stem cell genome effort as part of a “revolution.”

“Genomics is going to become a key part of all of our lives whether you like it to be or not,” he says on his blog.

“Right now, in a lot of ways, doctors are making educated guesses as to how to treat us patients more generally,” Knoepfler says. “By knowing our genomic information, our genotype – the information tucked away in our genomes –they could be making far more educated choices about treatments, and we could be making far more informed decisions about our health.”

The National Institutes of Health says that genes play a role in nine out of the 10 leading causes of death in this country. “Genomics is helping researchers discover why some people get sick from certain infections, environmental factors and behaviors, while others do not,” the institute says.

The nascent field is not without controversy. The U.S. Food and Drug Administration recently cracked down on the Google-backed genetics firm 23andMe of Mountain View, saying that it had failed to show that its testing produced accurate results. The company last month said it would stop providing health information with its tests. The danger to the public, say some medical experts, is that people might act on inaccurate or poorly understood genetic information and unnecessarily undergo drastic or harmful procedures intended to ward off future disease.

Such concerns haven’t slowed growth in the genomics industry, however. Various studies say that the current annual sales of genomic products exceed $3 billion and peg the annual growth rate at anywhere from 10 percent to 17 percent.

The stem cell agency two years ago this month sized up the situation and decided it was time to jump in. The agency’s governing board gave the go-ahead – on a voice vote with virtually no discussion – to the concept behind this week’s awards. CIRM directors had already been primed at the time by a presentation by Craig Venter, head of the La Jolla Institute bearing his name and internationally famed for his genomics work. Venter told the CIRM board that “there will not be any clinical stem cell applications without understanding genomics.”

Venter said genomics is needed to tell whether a particular stem cell therapy will cause more harm than good. Venter also told the board that he already had embarked on a stem cell genome effort. He is believed to be competing for the CIRM funding, and his talk raised eyebrows among some researchers because it was so closely tied to the board action.

The agency opened the door to applications from researchers and institutions in October 2012, eight months after the talk by Venter, who appeared at the agency’s invitation. The review of those applications and the identities of the applicants are cloaked in secrecy, which is the traditional way scientific grants are awarded in this country even when they involve public funds.

A combination of out-of-state scientists and six CIRM board members scores the grants and makes its decisions. The full, 29-member CIRM board will have the final say in a public meeting in Berkeley on Wednesday, but it almost never departs from the recommendations for approval by its reviewers. CIRM announces only the names of the winners and does not release the names of rejected applicants because it might embarrass them.

Last week, CIRM President Alan Trounson and his staff recommended funding only one of the applications – for $33 million – although reviewers had approved four, according to documents at the CIRM website. No public explanation was immediately provided, except that CIRM spokesman Kevin McCormack said the reviewers actually “did not recommend funding all of the applications,” although that was clearly stated on the website, as has been the practice on the review of thousands of previous applications.

The funding round is budgeted for $40 million, but could be more or less depending on the wishes of the board.

A number of the major educational institutions in the state are likely to be involved in this week’s awards. Stanford University’s name surfaced last year when a conflict-of-interest violation in the initial grant review was reported by the California Stem Cell Report. CIRM grant reviewer Lee Hood of Seattle, renowned internationally for his genomics work, acknowledged that he had failed to disclose his conflict in connection with a $24 million application involving Irv Weissman, director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine.  Weissman and Hood are longtime friends and own property together in Montana.

The closed-door review also marked the first time in CIRM’s history that reviewers, all from out of state, failed to finish with a decision supporting any of the proposals, according to CIRM. Reviewers’ comments were sent back to applicants, who resubmitted their proposals for review in November in another closed-door session. This time, Hood did not participate.

In addition to Stanford, California enterprises that have a strong interest in genomics and that are possibly involved in the competition include: Illumina and Sequenom of San Diego, Life Technologies of Carlsbad, CombiMatrix of Irvine, Pacific Biosciences of Menlo Park and Complete Genomics of Mountain View, which is owned by BGI, a Chinese business that is the largest genomics sequencing firm in the world. Others include Scripps, the San Diego Supercomputer Center at UC San Diego, the Novartis Genomics Institute and Fate Therapeutics, both of San Diego, and UC Santa Cruz.

UC Davis has just begun an $18 million genome operation in partnership with BGI, but Richard Michelmore, director of the Davis Genome Center, said it was not involved in any of the CIRM applications. (Ken Burtis, who is a member of the faculty of the Davis Genome Center, is a member of the CIRM governing board.)

The expected winner of the $33 million award is a group headed by Stanford University’s Michael Snyder, director of its Center for Genomics and Personalized Medicine, based on documents posted Friday on the stem cell agency’s website.

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David Jensen publishes the California Stem Cell Report – californiastemcellreport.blogspot.com --and has followed the stem cell agency since 2005.

California's $40 Million Genomics Round: Charges of Unfairness, Factual Error and More

Scientists at two major California research institutions have leveled charges that the state stem cell agency's $40 million genomics round is tainted with unfair and non-scientific considerations along with factual errors, manipulation of scores and apparent preferential treatment.

The statements were contained in letters (see here and below) to the governing board of the state agency from researchers at UC San Francisco and the Scripps Research Institute in La Jolla, who were competing in the round. The allegations involve the agency's closed-door grant review process in which a seven-member consortium led by Stanford University appears the likely winner.

CIRM President Alan Trounson has recommended approval of Stanford's $33 million bid. It was the only application that he supported out of four recommended for funding by CIRM's prestigious grant reviewers. Trounson also specifically recommended not funding the three other applications, including those from UCSF and Scripps. The board's longstanding practice has been to fund all awards recommended by reviewers.

Pui-Yan Kwok
UCSF photo

Pui-Yan Kwok, leader of the UCSF bid, and Jeanne Loring, who heads Scripps effort, have taken their complaints about the process to the agency's 29-member board which meets Wednesday in Berkeley to act on the applications to create one or two stem cell genomics centers in California.

In an e-mail to the California Stem Cell Report today, Kwok said his team has examined the summaries of the grant reviews posted on the CIRM Web site. He said,

“We were surprised to see that the genomic center scores of the top two applications were based on the reviewers removing from consideration the poorest performing center-initiated projects.  The fact that the reviewers could propose removal of individual center-initiated projects was never mentioned in the RFA. 

“Even more appalling is that this was applied only to the two applications (that) ended up with the highest scores.  The end result is that two centers' scores were artificially inflated to 88 and 82, respectively.  Despite this uneven application of the review process, two other applications received Tier 1 (recommended for funding) scores.  This appearance of preferential treatment makes the process suspect."

In his letter late yesterday to the board, Kwok said such actions are “inconsistent” with practices of the National Institutes of Health, whose standards are the norm for virtually all scientific grant reviews. The stem cell agency's review practices are patterned after those of the NIH.

Jeanne Loring
Scripps photo

In her letters to the board and the CIRM staff, Loring addressed four major factual errors that she said were made by reviewers. They ranged from a belief by reviewers that the RFA sought a matching financial commitment from applicants to a belief that Loring's partner in the project, Illumina, Inc., of San Diego, would not make its scientific tools easily available to researchers.

Loring said, however, the only “serious concern” expressed by reviewers in the CIRM review summary was the “lack of material commitment” from the applicants.

Loring said,

“This comment...suggests that other applications did offer to provide extra money for their (genomic) centers. Since there was no written request for additional funds, and we were not informed that contributions would be expected or considered as a measure of scientific merit, we were put at a significant disadvantage.”

(Reviewers praised the Stanford application for its “very substantial matching funds from multiple participating institutions.”)

Loring also stressed the benefits of the partnership with Illumina, a world leader in genomics. The firm recently announced a device that can sequence a human genome for $1,000, which sent its stock jumping this month. She said that Illumina's sequencer is the only one approved by the FDA for clinical diagnostics. She said that partnering with Illumina will give researchers access to tools that can have an “immediate impact” on their clinical studies on cancer, heart disease and inherited diseases.

(On Jan. 27, the agency released a statement defending its procedures. An item dealing with that can be found here.)

The stem cell agency has long come under fire from the biotech community because of the tiny percentage of its funding that goes to industry. Loring noted that last week that the only body charged with overseeing the finances of the agency, the Citizens Financial and Oversight Committee, stressed that it was necessary to form partnerships with industry.

In addition to Illumina, Loring is working with researcher Nicholas Schork, who this month joined Craig Venter's institute in the San Diego area. Venter is internationally famed for his genomics work. She said that the linkage with the institute will provide her project with “even broader access to genomic expertise.” The Venter Institute is involved with the Stanford application as is UC Santa Cruz.

Illumina also sent a letter to the CIRM written by Mostafa Ronaghi, the company's senior vice president and co-project director on the Loring application. Ronaghi said that Illumina makes affordable research tools and will help with planning experiments and analysis. Also involved in the Scripps-Illumina bid is co-investigator Jian-Bing Fan of Illumina.

Kowk said Ophir Klein of UCSF and Steven Brenner of UC Berkeley are co-directors of their effort. Other researchers involved are Michael McManus, Joe Costello, Susan Fisher, Neil Risch and Arnold Kriegstein, all of UCSF; Lin He and Dan Rokhsar, both of UC Berkeley, and Amander Clark of UCLA.

The California Stem Cell Report has queried Stanford concerning a list of its participants.

The names of the other applicants in genomics round are not known. The stem cell agency will not release the names of winning applicants until after the board acts and never releases the names of rejected applicants. The agency also withholds the names of applicants from the board prior to its action on them unless the applicants “self-identify,” usually in the form of letters to the board, which are a public record. Board members also do not have access to the actual application nor does the public. Some board members have complained in the past about not having enough information to act when applicants appear directly before the board.

Directors have final legal say on all applications. They do not, however, have to act on any of them. They can increase funding beyond the $40 million originally budgeted for this round or lower it. They can also send the applications back to reviewers for reconsideration or approve them with conditions.

Here is a copy of Kwok's letter, which the stem cell agency has not yet posted.

  UCSF letter re $40 Million California Genomics Round by DavidJensen

Stanford Genomics Consortium Likely Winner in $33 Million Stem Cell Agency Project

A seven-member consortium led by Stanford University's Center for Genomics and Personalized Medicine is expected next week to win a $33 million award from the California stem cell agency to create a stem cell genomics center.

Michael Snyder
Stanford photo

Information confirming the identity of the likely winner was posted on the CIRM Web site today. It came in the form of a letter from Michael Snyder, director of the Stanford genomics center.  In the document, Snyder told stem cell agency directors that his group is “very pleased with the overall enthusiasm” for its
application.

CIRM's reviewers gave the proposal an overall scientific score of 88 and recommended it for funding. It was the only application in the genomics round that was also supported by CIRM President Alan Trounson and his staff.

Trounson recommended no funding for the three other applications that the agency's prestigious reviewers had approved for cash.

The board is certain to hear presentations at its meeting next Wednesday from one or more of the applicants that were rejected by Trounson and his staff. The board has final say on all applications and can add or subtract money for the genomics round, which is budgeted for $40 million.

The nine-year-old practice of the board has been to fund virtually all of the applications backed by its scientific reviewers, all of whom come from out of state. Trounson's recommendations would represent a sharp departure from that practice.

Earlier this week the agency offered no public rationale on its Web site for its recommendations to reject the reviewer-backed applications. However, either late yesterday or early today, a CIRM document dated Jan. 15 was posted by the agency that provided more information. The terse statement said that the Stanford proposal – with the changes recommended by the CIRM staff –  “will fulfill all of the aims of the RFA and provide an excellent, responsive and comprehensive genomics resource for California stem cell researchers.”

Snyder's letter to the CIRM board asked it to approve Stanford's entire application and rebuff staff recommendations for changes. He said that some of the grant reviewer objections were “based on material errors of fact or scientific details that were not explicitly addressed in the proposal due to space limits.”

Stephen Quake
Stanford photo

Michael Clarke
Stanford photo

Snyder's letter also identified two other Stanford researchers involved in the project:  Stephen Quake, a professor of bioengineering, and Michael Clarke, associate director of the Stanford stem cell institute headed by noted stem cell scientist Irv Weissman. Clarke was identified as a “collaborator” and Quake as a principal investigator on one of the consortium's projects.

None of the other competing institutions was identified by CIRM. The stem cell agency does not release the names of winners until after the board acts on their applications. The agency never releases the names of rejected applicants for fear of embarrassing them.

CIRM's summary of the grant review said the Stanford proposal involves seven major academic and nonprofit institutions that are providing “very substantial matching funds.”

The summary continued,

“Although some reviewers expressed minor concerns that the multiple, geographically separated components of this large and interdependent program could pose an administrative challenge, overall, reviewers expressed much confidence in the demonstrated abilities and collaborative experience of the program leaders for achieving a shared vision.”

Reviewers cited as a “major strength” the ability of applicants to handle the processing of massive amounts of data needed for genomics research. The summary said,

“The leader of this center component is a pioneer in the field and has an outstanding track record in the proposed activities.”

California's Stem Cell Genomics Awards: An Untidy Affair

The California stem cell agency's $40 million genomics round seems to be turning into a bit of a muddle.

The agency's Web site said this week that four applications were approved for funding by CIRM's prestigious grant reviewers, whose recommendations go to the agency's governing board next week. However, CIRM President Alan Trounson and his staff are recommending that only one of those applications, a $33 million proposal, be approved by the board. Those other recommendations from reviewers, the agency said today, are not really recommendations.

Alan Trounson
CIRM photo

The move by Trounson, who announced last fall that he is leaving the agency, reflects the most aggressive action taken by the staff on grant applications since they began making recommendations on them last year. 

As of this writing, the CIRM Web site has yet to offer a rationale for the staff's recommendations. The review summaries of the applications said simply, 

"CIRM Staff Recommendation: Do not fund"  

So the California Stem Cell Report queried the agency this morning about the matter.

Kevin McCormack, CIRM's senior director for communications, replied that the reviewers actually “did not recommend funding” the three out of the four applications despite what the agency officially says on its Web site. The language and graphic on the Web site, however, conform to the agency's practice involving thousands of applications over the last nine years. Its governing board has been exquisitely careful to heed the positive recommendations of its reviewers. 

The unusual situation – not to mention the dollars at stake -- seems certain to trigger public presentations by rejected applicants at the governing board's meeting next Wednesday in Berkeley. The board can override both staff and reviewer recommendations as well as increase or decrease the money available for the genomics round.

To fully understand the muddle, it is necessary to understand some details of the CIRM grant review process. The CIRM Grants Working Group -- composed of six voting CIRM board members, and a long list of out-of-state scientists plus other experts from time to time, or some subset of the group -- examines the applications behind closed doors. The scientific members score the grants and then they are voted on by the full panel. The results of the reviewer decisions are presented to the public in tiers. Tier one is invariably funded by the board with no discussion at the later public board meetings. In the history of CIRM, only one or two applications have been downgraded from tier one. The definition of tier two has varied, but these basically are wobblers – applications with some merit but not quite enough to win approval from reviewers. Occasionally the board reaches into tier two to approve an application. Tier three applications are not recommended for funding by reviewers.

Four applications for funding to create stem cell genomics centers were placed in tier one, according to documents on the CIRM Web site this week. Their scientific scores range from 88 to 75. A fifth application was scored at 70 and placed in tier two. The names of the applicants were withheld in keeping with CIRM's practice. The agency only announces the names of winners. CIRM says it withholds the names of rejected applicants to avoid embarrassing them.

Here is McCormack's full explanation for the variation between the longstanding practice of the agency and what has happened in the genomics round.

“Tier 1 in this case really means 'fundable' as in adequate for funding.  Assignment to this tier was based solely on scores from scientific review.  Reviewers understood that only one or possibly two centers would be funded (that was clearly stated in the RFA) and did not recommend funding all of the applications.”

McCormack is correct that the RFA said one or two. Most CIRM RFAs have similar language. The RFA for the basic biology round, also to be considered on Wednesday, for example, says that as many as 30 grants may be awarded. It could be less, and it could be more depending on the board's druthers.

In the past, CIRM staff has offered the board a brief written statement supporting their recommendations on applications. Presumably that will be posted on the CIRM Web site soon.

Craig Venter
Venter Institute photo

The latest situation is not the first unusual event in the genomics round, which began publicly two years ago this month at a CIRM board meeting in San Diego. It was then that the board approved the concept for the $40 million round on a voice vote with almost no debate. The CIRM directors had already been primed by 30-minute presentation by Craig Venter, the famed genomics expert who heads the San Diego area institute bearing his name. Venter, who was invited to appear by the agency, built a case for the importance of genomics and said he had already begun a stem cell genomics effort. He is believed to be one of the competitors for next week's funding for CIRM. His presentation raised eyebrows among some scientists because of its close tie to the board vote on the plan.

The genomics round was also marked by a conflict-of-interest violation last year involving eminent Stanford stem cell researcher Irv Weissman and Lee Hood of Seattle, renowned internationally for his genomics work. Hood had been recruited by Trounson to be a reviewer in the round. However, at the review session, Hood failed to disclose his relationship to Weissman, who was involved in a $24 million application from Stanford. They are longtime friends and own property together in Montana.

Reviewers at that session were unable to come up with recommendations for funding. It was the first time in CIRM history that has occurred. The reviewer comments were subsequently sent back to applicants who resubmitted their proposals for review last November.

As for the $33 million proposal recommended by Trounson and his staff, the review summary says it involves seven major academic and nonprofit institutions. The review said the applicants are offering “very substantial matching funds.”

The institutions are also widely scattered. The review summary said,

“Although some reviewers expressed minor concerns that the multiple, geographically separated components of this large and interdependent program could pose an administrative challenge, overall, reviewers expressed much confidence in the demonstrated abilities and collaborative experience of the program leaders for achieving a shared vision.”

The study of genomics also requires manipulation of massive amounts of data, a matter of importance to reviewers. The review summary said that aspect of the proposal was a “major strength.” The summary said,

“The leader of this center component is a pioneer in the field and has an outstanding track record in the proposed activities.”

During its public discussion of grant proposals, the CIRM board is not told the name of the applicants. It only works from the public summary of the proposal and does not see the actual application. Board members with conflicts of interest are prohibited from engaging in the discussion or voting.

Jerry Brown: California Leads the Way on Stem Cell Research

Governor's office photo

California Gov. Jerry Brown this week praised the state's biotech industry, specifically mentioning stem cell research as example of leadership in medicine.

While he did not mention the stem cell agency by name in his state of the state speech yesterday, it was clear that he thought highly of its efforts. Here is what he said, which BayBio, an industry group, highlighted on its Web site.

“California is the nation’s leader in developing medical and scientific advances that will cure diseases and lower costs. We have six of America’s twelve top-performing metropolitan areas in biotechnology: San Diego, San Jose, San Francisco, Oakland, Los Angeles and Orange County. Last year, we created a tax credit to help innovators, in these regions and beyond, hire and expand in California. Four out of the world’s twenty leading academic bioscience institutions are located here in California: UCSF and Berkeley, UCLA, Stanford and UC San Diego. Just as California has led the way with stem cell research, so too can we pioneer the new field of precision medicine which uses genomics, medical devices, computer sciences and other fields to treat individual patients, instead of broad populations.”  

California Stem Cell Agency to Hand Out $80 Million for Stem Cell, Genomics Research

Directors of the California stem cell agency are set to give away up to $80 million late this month as they pursue their efforts to turn research into cures.

The most attention-getting award round would create one or two stem cell-genome centers in California that the agency says will advance medicine and make the Golden State a world leader in stem cell genomics. Cost of the effort could run as high as $40 million.

The initial review of the applications last year was marked by a conflict of interest involving reviewer Lee Hood of Seattle, Wash., an internationally known genomics researcher, and Irv Weissman of Stanford, who was involved in one of the applications. The conflict was first reported by the California Stem Cell Report and subsequently received attention in international scientific publications. 

The other $40 million round (possibly 30 awards) is a continuation of the agency's basic biology funding. CIRM, however, is increasingly turning towards research that is either in a clinical trial or close to one. It is seeking to fulfill the promises of the 2004 ballot campaign that created the agency and also to create some excitement that will lead to more funding of the agency, which is scheduled to run out of cash in less than three years.

Also on the agenda for the Jan. 29 meeting in Berkeley is the search for a new president and unspecified changes in CIRM rules that deal with research involving human eggs. More details are expected to appear on the agenda in the coming week along with summaries of the grant review applications and scores.

The California Stem Cell Report will have more on the genomics round also in the coming week.

CEO Search at California Stem Cell Agency: Board Discussions Set for Late This Month

Directors of the $3 billion California stem cell agency late this month will act on what it calls a “candidate position statement” in its search for a new president for the research effort.

The agency scheduled a meeting Jan. 28 of its Presidential Search Subcommittee to consider the document, which was not available on the CIRM Web site as of this writing. On Jan. 29, the full CIRM board is expected to act on the document at its meeting in Berkeley.

The agency's agenda material did not specify what it means by a “candidate position statement.” In normal parlance, a candidate position statement is offered by a person seeking a position. Our best guess is that what CIRM is considering is a document that would specify the positions that it would like a candidate for president to address. The board last month approved a statement of criteria that implied that candidates should address certain questions. We are querying CIRM concerning the matter.

Both the subcommittee meeting and the full board meeting include closed-door sessions during which the search for a new president will be discussed. The current president, Alan Trounson, has announced that he is resigning to return to Australia. Directors of the agency have said they are emphasizing speed in selection of a replacement. Trounson announced his departure more than three months ago.

Teleconference locations for the subcommittee meeting Jan. 28 where the public can participate are located in La Jolla, San Francisco and Costa Mesa. The base for the meeting is at the Claremont Hotel in Oakland. Specific addresses can be found on the agenda. 

Big Sangamo Deal for California Stem Cell Agency with an Asterisk

It was a $20 million deal -- possibly as much as $300 million --for Sangamo BioSciences, and its president told the California stem cell agency,

“We wouldn't be where we are today without you.”

The $3 billion agency has pumped $5.4 million into the publicly traded Richmond, Ca., firm for HIV/AIDS research and another $6.4 million last May for a phase one clinical trial dealing with beta-thalassemia, a genetic blood disease.

Last week Sangamo announced that Biogen Idec of Cambridge, Mass., would buy into its research related to beta-thalassemia as well as sickle cell anemia. The announcement said Biogen Idec will also reimburse Sangamo for “its internal and external research and development program-related costs.” Payments of up to another $300 million could come Sangamo's way if it meets certain goals.

Kevin McCormack, CIRM's senior director of public communications,wrote on the agency's blog that it has been “a very good start” in 2014 for CIRM. He noted that the Sangamo announcement followed similar good news from Capricor, another CIRM grant recipient that has announced funding from Big Pharma.

He quoted Ellen Feigal, senior vice president at the agency, as showing how “important the funding we provide is in helping companies like Sangamo get their research to a point where big pharmaceutical companies stand up and take notice, and invest.” 

McCormack wrote that Edward Lanphier, president of Sangamo, sent an email to CIRM in connection with the announcement that said,

"Thank you for ALL of your support over the past several years. We wouldn't be where we are today without you."

The Sangamo deal, however, has an asterisk. In May 2012, a “special advisor” to the stem cell agency, Saira Ramasastry, was nominated to the seven-member Sangamo board of directors. Following an item in the California StemCell Report, the agency announced that her contract was not being renewed. CIRM said she was not involved in a decision-making role and was not required to file a statement of economic interests with the agency. Ramasastry subsequently was elected to the Sangamo board where she still holds a seat.

Sangamo's stock closed at $19.84 today, up 46 cents. Its 52 week high is $20.33 and its low $6.86.

Our take: The investment in Sangamo is a healthy sign of expanding interest from larger firms in stem cell therapies. However, it is darkened by the "revolving door" situation involving Ramasastry. CIRM does not require public disclosures of the financial interests of its consultants. Nor does it restrict revolving door arrangements with them that permit later employment at CIRM-connected firms. At the same time, the agency is moving aggressively to engage industry ever more closely and to generate results that will resonate with the public. The agency would do well to heed the conflict-of-interest study from the prestigious Institute of Medicine in 2009. Bernie Lo of UCSF was one of the editors of the study. He wrote that medical research and the private sector have sharply divergent priorities and sometimes irreconcilable differences. The stem cell agency should act to ensure that both the appearance and reality of cronyism, insider dealings and conflicts-of-interest do not blemish its scientific track record.

Changes Made in Tobacco Tax/Stem Cell Proposed Ballot Measure

The proposed tobacco tax initiative that could provide roughly $200 million a year to the California stem cell agency has been revised by its backers, although the changes initially appear not to affect the potential cash for the research effort.

Backers of the effort reported the changes today after the original version of the proposal dropped off the state attorney general's Web site this week, its first stop on the way to qualifying for the ballot.

In response to a query from the California Stem Cell Report, attorney Phil Kohn of the Rutan & Tucker law firm of Costa Mesa said the measure had been altered and was being resubmitted. We asked him to indicate the nature of the changes and their location in the document. He replied,

"There is a language change in Section 3(a) of the 'Purpose and intent' portion.  In addition, the following sections of the Act were modified (in minor part):  130161, subdivisions (e)(1), (e)(2) and (e)(3); 130163, subdivision (d)(2); 130164, subdivisions (c)(2) and new (c)(4); and 130165, subdivisions (b)(2) and new (b)(4)."

He also said that the Frank Barbaro of Santa Ana, the man responsible for the initiative, is a litigation lawyer and is currently deeply involved in a trial matter. He said Barbaro, who is also the former chairman of the Orange County Democratic Party, will elaborate on the initiative once he is free of his pressing professional obligations.

Here is the initial version of the ballot measure.

  Tobacco Tax Stem Cell Initiative Version 1 -- 2014

Here is the latest version of the ballot measure as provided by Kohn.

  Tobacco Tax Stem Cell Initiative Version 2  --2014