$1 Million Evaluation of Stem Cell Agency Comes Up Next Week

Directors of the California stem cell agency appear ready to commission a $1 million “gold standard” study of its operations with the hope that it will pave the way for voter approval of billions more for stem cell research, perhaps as early as November 2012.

The proposal is scheduled to be voted on at the CIRM board meeting next Wednesday and Thursday meeting at Stanford. However, few details of the latest version of the plan are currently available on the CIRM Web site.

Nonetheless, some information can be gleaned from the transcripts of the directors' Science Subcommittee meetings in May and July, when the proposed study was discussed.

Here is what we have been able to extract. The study would be performed by the prestigous Institute of Medicine(IOM). The cost would be in the $1 million range. CIRM Chairman Robert Klein is proposing that about half of the amount would come from private donors. In July, Klein referred to a 15-month timetable, which might be quite speedy for the Institute of Medicine, which moves slowly, according to the transcripts. If work begins in January, the study could be completed in time for the presidential election in the fall of 2012. Politically speaking, that is the likely to be the best time to seek approval of another multibillion dollar bond measure, given the larger voter turnout in presidential elections. Klein, however, did not mention a specific election timetable.

During the two subcommittee meetings, no CIRM director raised the possibility that the study would identify serious flaws in the agency's $3 billion operation. Klein predicted that the study “would be a solid milestone.”

Jeff Sheehy, chairman of the Science Subcommittee and a communications manager at UC San Francisco, said the IOM would provide a “gold standard objective evaluation.”

Sheehy continued,

“I certainly don't want to go off the board in two years without this report being finished. I don't think I could go to any member of the public, any editorial board, any member of the legislature, the governor, any elected official without some sort of external review of what's gone on with a billion dollars of the taxpayers money, especially in the middle of this horrible recession.”

Sheehy noted that the IOM is less than a household word. In May, he provided this description,

“The Institute of Medicine is an independent nonprofit organization that works outside government to provide unbiased and authoritative advice to decision makers and the public. established in 1870, theIOM is the health arm of the National Academy of Sciences, which was chartered under President Abraham Lincoln. The IOM asks and answers the nation's most pressing questions about health and healthcare. And the aim is to help those in government and the private sector make informed health decisions by providing evidence upon which they can rely.”

During the Science Subcommittee meetings, CIRM directors often referred to the IOM's vaunted independence, which they implicitly did not think would be affected by a $1 million contract. There also was no discussion of limitations that CIRM might impose on the scope of the study before signing a contract. In the case of a current $300,000 contract to assess the economic impact of the agency, CIRM specified that its economic consultants must “execute a vibrant and aggressive strategy” supporting CIRM, a requirement that fundamentally damages the credibility of whatever the their report says.

At subcommittee meeting in July, CIRM Director Philip Pizzo, dean of the Stanford School of Medicine and a member of the Institute of Medicine, said,

“Of any organization that I'm familiar with on a national level, there isn't any other that carries the weight of independence and critical review (of) the IOM and the National Academy of Sciences.”

Klein, who ran the 2004 Prop. 71 campaign that created the organization he now chairs, repeatedly framed the study in the context of a ballot campaign. He said he wanted it “finished in time that the public can analyze it before we go back and put forth the question about whether we're entitled to more bonds.”

Klein did not publicly identify potential donors to help pay for the study. A question could be raised about whether he or others intend to solicit funds from persons who have financial ties to enterprises that would stand to benefit from CIRM funding.

Directors acknowledged that the $1 million price tag appears steep. However, it is a tiny amount when compared to the $6 billion cost (including interest) of the stem cell research effort.

Klein's support for an IOM study seems to be in some contrast to his previous complaints about the amount of scrutiny (audits and otherwise) that CIRM has received from various sources. This spring, the agency also successfully stripped out of pending legislation a requirement that the state controller, who chairs a Prop. 71-created panel to oversee CIRM finances, commission an independent performance audit. Instead, the now CIRM-backed legislation (SB1064) places that audit squarely in the hands of the stem cell agency.

At the July meeting, Klein mentioned a proposal from the IOM. We have asked CIRM for a copy of that document.

Leadership and Small Things

Author and Harvard business professor Rosabeth Moss Kanter weighed in this week on “big traps in small lapses.”

The case in point was the recent resignation of HP CEO Mark Hurd, a man who made more than $66,000 a day, because he fudged a $20,000 expense report.

Kanter asked,

“How can very smart, accomplished people do such stupid things?”

Kanter, whose 18 books have won her recognition as one of the 50 most influential business thinkers in the world, noted that Hurd has a fair amount of company.

“Hurd is not the first, and probably won't be the last, top leader to fall from grace over seemingly trivial and avoidable lapses of judgment.”

Citing several cases ranging from the US military to politics, she said the underlying causes include embarrassment (fear of disclosure), lack of attention and arrogrance.

Her bottom line:

“As is often said, the devil is in the details — and so is the angel. Signs of character are most visible when they are least visible — that is, demonstrated by what people do when they think no one is watching, such as following the rules or taking the moral high ground with no audience observing them. That's why the signals of a leader's judgment lies in the small things.”

Her comments apply to leadership in any organization.

Cedar-Sinai's Melmed Named to CIRM Board

Shlomo Melmed 

The governing board for the $3 billion California stem cell agency has a new member – Shlomo Melmed, who is senior vice president for academic affairs and dean of the medical faculty at Cedars-Sinai Medical Center in Los Angeles.

Gov. Arnold Schwarzenegger named Melmed to replace Ricardo Azziz, who left California to head the Medical College of Georgia. Azziz was also a top executive at Cedars-Sinai.

The Cedars news release last week on the appointment said,

“Melmed, the Helene A. and Philip E. Hixon Chair in Investigative Medicine at Cedars-Sinai, is an internationally recognized endocrinologist and specialist in pituitary disorders. His research, which is primarily focused on the regulation of growth hormones and causes and treatments of pituitary tumors, has impacted endocrine care worldwide, and has consistently been funded by the National Institutes of Health since 1980.

“He has authored more than 300 articles in prestigious peer-reviewed journals, trained more than 60 physicians, scientists and graduate students, and played a major role in leading the growth of research and educational programs at Cedars-Sinai.”

Melmed is also professor and associate dean at the UCLA School of Medicine.

(Cedars-Sinai photo)

Emotionalism and Potential Favoritism Cited as Need for Changes in CIRM Grant Appeals

Passion and favoritism, democracy and gamesmanship – all are part of the ongoing discussion among directors of the $3 billion California stem cell agency as they try to fix what some of them call a “broken” grant appeal process.

Hundreds of researchers will be directly affected by whatever decisions the governing board might make. The agency still has roughly $2 billion to hand out.

Indirectly affected are patient advocates and others who may think that research that could help them -- and others like them -- is receiving short shrift.

CIRM's directors have been bedeviled for more than 2 ½ years by appeals from researchers whose applications have been rejected by grant reviewers. It wasn't an issue up to that point because most rejected researchers did not avail themselves of the opportunity to make a personal pitch to the board – an action that they are entitled to under state law. Either scientists weren't aware they could speak to the board directly, as any member of the public can, or they weren't brazen enough to do so.

The directors' new Science Subcommittee has taken up the extraordinary petition process in two meetings this year. But nothing has been heard at those meetings from researchers. One likely reason is the agency's failure to make public in a timely fashion a draft of what they are considering. In July, a proposal for “re-scoring” rejected applications, under certain circumstances, was not made available to the public until one business day before the subcommittee meeting.


Jeff Sheehy, a communications manager at UC San Francisco, is chairman of the Science Subcommittee. A patient advocate member of the CIRM board and a member of the grants review committee, he is one of those who describe the petition process as broken. None of the 29 CIRM directors has expressed satisfaction with how petitions are handled.

At the July Science Subcommittee meeting, Sheehy noted that “a lot of applicants” see no disadvantage to filing a petition and consume an “an enormous amount” of CIRM staff time. According to the transcript, he said the petitions have degenerated into “gamesmanship.” Sheehy said, however, the ability of any person to appear before the CIRM governing board is a “positive feature of the California public policy process.”

CIRM director Joan Samuelson, also a patient advocate member of the board, said,

“I don't see it as a broken system exactly. There are concerns about it. But maybe it's like democracy. We're not nuts about it, but it's the best we've got.”

CIRM divides its grant appeal process in two ways. One is formally called an appeal. It is handled behind closed doors, but probably shouldn't be, and involves conflicts of interests. The staff makes decisions on those issues, although they could be raised publicly by a researcher if he or she chose to do so. Over the past few years, more scientists came before directors seeking reconsideration on other grounds. As a result, the board created something called an extraordinary petition, which is just another way of appealing a negative decision by reviewers.

This spring, nine researchers filed petitions, nearly one-third of rejected applications that were rejected. Four petitions were successful. The process, however, tested the patience of the board.

Some scientists have appeared before the board backed by a small cadre of patient advocates for diseases and persons suffering from serious afflictions, which has raised concerns about the role of emotions in making funding decisions. The presentations are powerful. It would take a cold, cold individual not to be swayed.

In July, CIRM Director Philip Pizzo, dean of the Stanford School of Medicine, brought up what he described as the “emotional overtone” of the presentations. He said that board members understandably respond “when someone speaks with deep concern and passion, particularly about a member of their own family.”

Sheehy responded,

"To be perfectly honest, Dr. Pizzo, that was one of the driving forces for this policy because a lot of times I find myself compelled by emotion, and I've lost the science.”

Sheehy said the re-scoring plan could evaluate a petition in “an atmosphere where there is no emotion.”

CIRM Director Oswald Steward, director of the Reeve-Irvine Research Center at UC Irvine, said he did not think that a new policy was needed on re-scoring. He said that directors already have the power to send back a grant for re-evaluation, although that has never happened as far as we know. It would seem to require nothing more than a vote of the board. However, no procedures are in place for staff to deal with such an action.

Steward also discussed how petitions can lead to favoritism. In the normal CIRM grant approval process, the names of applicants are not disclosed when their applications come before the board. However, in some cases it is not too difficult to determine their identities. But under the petition process, the researchers are required to publicly identify themselves, even if they do not appear before the board. The board also does not have copies of the actual applications, only a summary of reviewer comments.

Steward said,

“This is a more fundamental thing, and I've been thinking about this in terms of this whole issue of extraordinary petitions. The thing that we most often run into is an investigator who, first of all, identifies themselves, which is really...one of the fundamental problems with this process, because if this is somebody we all know, we say, 'Oh, well, this person deserves some really extra attention.' And if it's not somebody we know, then maybe we pay less attention to it. It really is a fundamental...unleveling of the playing field.

“The problem that we most often run into is that whoever says...the reviewer missed this, or there's a mistake or whatever, and we have in front of us the letter from the investigator, but we're still unable to look at the grant itself or the comments of the review panel. So my specific proposal that now I'm going to make for all of the extraordinary petitions is that if an investigator wants to make an extraordinary petition, they should volunteer themselves to provide the (directors) with a copy of the original proposal and a copy of the review. In other words, let's get all the issues out on the table for our consideration.”

An odd bit of CIRM management muddle also surfaced during the July session. CIRM President Alan Trounson said he was not aware of the staff proposal for re-scoring grants and expressed reservations. Trounson's comments triggered some irritation on the part of Sheehy, who said he had been working for some time with CIRM staff on the matter.

No decisions were made last month on changes in the petition process. Another Science Subcommittee hearing is likely in the next couple of months.

California stem cell scientists do have something significant at stake in all this. Even if they cannot appear directly before the subcommittee, it is in their best interests to weigh in with constructive suggestions. They can be sent Gil Sambrano, the staff member who deals with grant reviews. His email address is gsambrano@cirm.ca.gov.

Stem Cell Directors Putting Off More Recruitment Grant Decisions

Directors of the California stem cell agency will meet for two days at Stanford University Aug. 18 and 19, and they are not scheduled to give away any money.

The board orginally was scheduled this month to approve some new, multimillion dollar recruitment packages for star researchers from out-of-state. The grant review group met in July to consider applications in the $44 million program. However, the matter is not on next week's agenda.

We are querying the agency concerning the absence of the awards. A number of possibilities exist. One is that no applications were of sufficient quality. Another is that the matter was delayed until a researcher is actually signed. That would avoid the awkward situation that occurred with the first recipient of the awards, Robert Wechsler-Reya of Duke. The board approved $6 million for him in April, although he had not yet made a decision to come to California and the Sanford-Burnham institute. He did not actually make a decision until last month.

Don Gibbons, chief communications officer for CIRM, said the award was postponed because "the candidate being brought forward wanted more time to notify their current

home institution."

(Editor's note: The preceding comment from Gibbons was not contained in an earlier version of this item.)

The board is also considering a proposal for another round of disease team grants, commissioning an expensive, Institute of Medicine study of CIRM and approving a policy that could lead to compensation of up $15,000 annually to patient advocate members of the board.

With only five business days remaining before the meeting, CIRM has listed only cryptic descriptions of the matters to be considered next week. It has failed to post on the agenda any material explaining exactly what the directors are planning to act on.

CIRM Directors Pay Proposal Advances; Another Openness Failure on Grants Management System

The California stem cell agency is set to pay 1/3 of its 29-member board of directors as much as $15,000 a year.

The action, however, is contingent on passage of legislation (SB1064) that is now in the “suspense” file in the Assembly Appropriations committee. Legislation in “suspense” is usually on hold pending action on the state budget, which is not likely to be adopted any time soon.

According to a CIRM spokesman, the agency's directors' Governance Subcommittee on Tuesday approved the new pay policy, which is aimed at compensating the 10 patient advocate members of the board for the extra time that they must put in. The policy will go before the entire board later this month.

A large part of the burden placed on patient advocate members of the board stems from the conflicts of interests built into the board by Prop. 71,  drafted by CIRM Chairman Robert Klein and a handful of others. The ballot initiative requires a super-majority (65 percent) for a CIRM governing board quorum, which is based on the number of board members eligible to vote. Since many of the board members have conflicts of interest that prevent them voting on matters before the board, the presence of patient advocates is necessary to take action – much more so than many other members of the board.

According to Don Gibbons, CIRM's chief communications officer, the subcommittee took no action on staff reports on CIRM's ongoing efforts to build a custom system to deal with its $3 billion in grants. Directors asked for a report after expressing concerns the effort could be an expensive failure. Details on their discussions will have to wait for release of the transcript.

However, once again, CIRM failed in its responsibility to the public by not posting the reports publicly in a timely fashion. The failure effectively bars the public from being able to make informed comments and violates CIRM's promise of highest standards of openness and transparency. Two reports were prepared. One did not appear until one business day before the Governance Subcommittee meeting. The other appears to have been posted on CIRM's Web site only minutes before the meeting was scheduled to begin.

We will have more on the grants management system when the transcript is posted.

Extremely Modest Coverage of Wechsler-Reya Signing; Status of Tannishtha Unclear

The signing of Duke stem cell “star” Robert Wechsler-Reya generated only one news story in California and none in North Carolina, where Duke is located, according to a Google/Yahoo search today on the Internet.

Other search engines, including Dogpile(an aggregator of search engines) and Bing, reported no stories on the successful multimillion dollar recruitment of the researcher to the Sanford-Burnham institute in La Jolla.

The lone article appeared in the San Diego Union-Tribune. Reporter Gary Robbins did not quote any officials from CIRM, which put up nearly $6 million as a signing bonus for Wechsler-Reya. But Robbins did specifically mention the agency and its recruitment program in the second paragraph.

Robbins quoted Josh Baxt, a spokesman for Sanford-Burnham, as saying,

"This is exactly what the award was meant to do: serve as a magnet. Dr. Wechsler-Reya is an ace, a star, who left a tenured post at Duke University to come here. We're very happy to get him."

The story said that Wechsler-Reya will be director of a 20-investigator tumor development program.

Robbins quoted the researcher as saying via email,

"I chose to move to Sanford-Burnham because of the diverse and vibrant research community there, and because of the tremendous resources the Institute offers for doing the kind of science I feel is important.

"The move will allow me to interact and collaborate with world-class cancer biologists and stem cell biologists, not only at SBMRI but in the broader San Diego area. I'm really excited about this opportunity, and look forward to being there."

We queried Sanford-Burnham yesterday concerning Wechsler-Reya's start date and the status of his spouse, Tannishtha Reya, also a Duke stem cell researcher.

A CIRM summary of the Weschler-Reya grant review last spring said,

“Reviewers also noted that the applicant institution has committed to recruiting the candidate's spouse, who is an independent stem cell scientist; this represents a particularly beneficial leveraging of award funds.”

Baxt replied by email,

“Dr. Wechsler-Reya will be starting around November 1. We cannot comment on Tannishtha Reya at this point.”

Neither scientist has responded to our queries regarding Reya's status with Sanford-Burnham.

It's Official: Wechsler-Reya Signs with Sanford-Burnham

The $6 million-plus recruitment of a Duke stem cell researcher to California seems certain to be the topic of considerable discussion this week in research labs around the nation, if not overseas.

The move – first reported by the California Stem Cell Report on Sunday – was officially confirmed today by the Sanford-Burnham Medical Research Institute in La Jolla and the California stem cell agency.

The agency put up $5.9 million in taxpayer funds in the form of a research grant. Sanford-Burnham added an “extremely generous commitment” to bring Robert Wechsler-Reya to the Golden State. He is the first recipient in CIRM's $44 million research leadership award program.

The stem cell agency's program is also likely the first of its kind in the nation. The Wechsler-Reya recruitment starts it off well, given its goal of bringing "franchise players" to California. The agency sent a message to stem cell researchers across the nation that they should be looking ever more closely at California if they want to move forward aggressively with their careers.

The effort also highlights the built-in conflicts of interest at CIRM. Potential beneficiaries of the program include 12 members of the 29-member CIRM governing board whose institutions could use the funds to lure talent.

Others outside of the state may not look kindly on the effort. It could increase the cost of retaining talent, which, of course, could lead to sweeter deals for researchers, even if they stay in place.

In California, some researchers may regard the recruitment as boosting the field generally. Others are likely to think the money may have been better used to fund scientists already in the state. Adding Wechsler-Reya to the pool of potential applicants for CIRM's remaining $2 billion also increases the competition.

Robert Klein, chairman of the California stem cell agency, said in a statement that scientists recruited through the effort will help develop innovative therapies and push CIRM's mission forward. He touted the effort as something of a job creation program for California, which is mired in a serious economic slump and a state budget crisis. Klein said,

“Bringing this caliber of scientist to California also creates high paying positions to staff the labs, providing new jobs and tax revenue to the state.”

The official statement from Sanford-Burnham today said that Wechsler-Reya was appointed professor and director of the Tumor Development Program in the institute’s NCI-designated cancer center.

The announcement quoted Wechsler-Reya as saying,

“The strength of the scientific community there, particularly in cancer biology, stem cell biology and neurobiology, is unparalleled. This move promises to transform the way we do science, and I am grateful to Sanford-Burnham and CIRM for making it possible.”

The news release did not mention Wechsler-Reya's wife, Tannistha, who is also a Duke stem cell researcher. We are querying the couple and Sanford-Burnham about whether she is also joining the institute, as was originally expected.

Oddly, CIRM's news release on the consummation of the deal seemed to downplay the monetary size of its role. It said that the grant to Wechsler-Reya was only $5 million, as opposed to $5.9 million.

California Gains Two Bright Stem Cell Stars from Duke

Robert Wechsler-Reya

Following a lengthy, multimillion dollar courtship, two Duke University stem cell researchers have decided to migrate to the Golden State's Sanford-Burnham Medical Research Institute, the California Stem Cell Report learned today.

Robert Wechsler-Reya is the first scientist to be recruited through a $44 million effort by the California stem cell agency. CIRM's board awarded him $6 million last April, although he was yet to make a final decision. Also believed to be coming to Sanford-Burnham is his spouse, Tannishtha Reya.

In addition to CIRM's signing bonus, Sanford-Burnham is providing “an extremely generous commitment of laboratory space, matching funds for equipment, additional support for relocation and research, and access to excellent core facilities,” according to CIRM documents.

Tannishtha Reya

An anonymous but well-informed source told us that the couple had made a final decision on the move to La Jolla in Southern California. We are querying the Duke researchers, CIRM and Sanford-Burnham for comment.

CIRM directors created the program last year to bring “paradigm-shifting” scientists – “franchise players” – to California. At least 12 members of the 29-member CIRM board are connected to institutions that can benefit from the program.

Look for more of what CIRM calls “research leadership awards” later this month. Reviewers met behind closed doors last month to pick some new, lucky recipients. Their decisions should go to the full CIRM board at its meeting later this month.

(Photos from the Reya and Wechsler-Reya labs)

Geron's Clinical Trial: Risk, Front-loading and Costs

The Vatican doesn't particularly care for the idea. "Unacceptable" was the word it used.

Over at Bioworld Today, it was "the dawn of a new era."

A reader of the New York Times warned of the danger of "front-loaded" arguments that can be detrimental to stem cell research.

What they were talking about is Geron and its re-vitalized clinical trial of an hESC therapy for spinal injuries. The FDA late this week lifted its hold on the effort. Andy Pollack of the New York Times said "cysts were discovered in some mice injected with the cells. Geron had to do another mouse study and develop better ways to check the purity of its cells."

Pollack wrote,

"Years of further testing will be required before the therapy would be proven and ready for widespread use, assuming it works."

Among the readers of Pollack's story was a person from Seattle who said,

"As in the case of most things in science, we just do not know enough to say which scientific modalities will bear fruit first if at all and when and hence multi-pronged approaches are needed. And the field of stem cell biology painfully realized a few years ago, some of these discoveries are fads that cannot be replicated by others ( I am referring to Catherine Verfaillie's assertion that adult stem cells can do most of what embryonic stem cells can do, a claim that has since been refuted/ withdrawn or generally agreed to be highly exaggerated at best). The damage done to stem cell biology from that fiasco is still evident. Hence most scientists would agree that front-loaded arguments for and against particular technologies are dangerous and can be detrimental to general scientific progress."

(Verfaillie is a CIRM grant reviewer.)

Over at UC Davis, stem cell researcher Paul Knoepfler, writing on his blog, called it a “milestone,” but noted that while the potential is high, the risk is very high as well.

Donna Young, Washington editor of Bioworld Today carried a detailed account concerning the trial. Her story began,

"The FDA's blessing Friday of the world's first clinical trial of a human embryonic stem cell (hESC) therapy has not only launched what may be 'the dawn of a new era' for medical treatment, but if successful, the therapies could alleviate much of the burdensome costs plaguing the nation's health care system, insisted Geron Corp. CEO Thomas Okarma."

Most of the news reports did not mention the seminal role of UC Irvine in the research leading to the clinical trial. You can find more details about that here on the Califoria Stem Cell Report.

Geron Go-Ahead Rouses Industry and Researchers

Geron Corp. said today that it hopes to begin within the next two months a clinical trial for an hESC therapy for spinal injuries, triggering a wave of ebullience from scientists, investors and patient advocates.

The company disclosed its plans following the lifting by the FDA of a hold on the effort.

Clive Cookson of the Financial Times of London caught the global significance. He wrote,

“The world’s first treatment based on human embryonic stem cells is set to begin a clinical trial within the next two months, in patients with acute spinal cord injury.”

For patient advocate Don Reed of Fremont, Ca., it was an emotional event. Writing on his blog, Reed said,

“The research behind this ground-breaking event was paid for a California law named after my paralyzed son, the Roman Reed Spinal Cord Injury Research Act of 1999.”
Reed continued,

“Christopher 'Superman' Reeve gave us his blessing, saying, 'One day, Roman and I will stand up from our wheelchairs, and walk away from them forever.' Cure did not come in time for our paralyzed champion, but we still believe in that great dream.”

Shares of Geron, a firm in Menlo Park, Ca., shot up 17 percent or 83 cents to $5.63. Analysts predicted skyrocketing share prices if the clinical trial proves successful.

Rob Waters and Molly Peterson of Bloomberg News interviewed Thomas Okarma, CEO of Geron. Bloomberg said,

"The FDA action strengthens Geron’s ability to start similar trials in the future, Okarma said. It also leaves regulators with a better grasp of how to review a completely new type of therapy.

"'It’s helped both of us to get up the learning curve together,' Okarma said. 'We’ve brought the FDA to a higher level of understanding which has been very positive and mutually beneficial. And phew, it’s about time.'"

Peterson and Bloomberg continued:

"Two other U.S. companies are working with embryonic stem cells. Advanced Cell Technology;of Marlborough, Massachusetts(and Los Angeles), is awaiting FDA approval to start a clinical trial in patients with Stargardt’s macular dystrophy, an eye disorder that causes severe vision loss.

"Viacyte, formerly known as Novocell Inc., a closely held San Diego company, is working on methods of turning embryonic stem cells into insulin-secreting cells for the treatment of diabetes."

Paul Knoepfler, a stem cell researcher at UC Davis, had predicted on his blog on July 1 that the FDA hold on Geron would be lifted “very soon.” Today he said,

"The hold was placed because of a 'higher frequency of cysts.' However many of us were wondering why the serious concern (and seemingly long hold) about non-tumorigenic cysts that were somewhat unremarkable in appearance. That remains unclear except that perhaps it was the "higher frequency" part. Despite being a bit puzzled about the length of the hold, I think in the long run caution makes sense."

CIRM President Alan Trounson said in a statement,

“This is an important milestone for the whole field to have an embryonic stem cell therapeutic in clinical trials. We are looking with hope and expectation that the transplant will be safe and effective.”

Geron is expected to be one of three firms (including Advanced Cell Technology) seeking funding from the California stem cell agency in its upcoming $50 million clinical trial round. The RFA was originally scheduled for May but was rescheduled for this month. CIRM appears likely to miss that target.

Pay Proposal for Patient Advocates on CIRM Board

The California stem cell agency is proposing to pay the 10 patient advocate members on its 29-member board of directors up to $15,000 a year for work performed in connection with their responsibilities for CIRM.

The move would implement some provisions of legislation that also removes the 50 person cap on the size of the CIRM staff. That legislation (SB1064) seems likely to be enacted this year. It is up for consideration in Sacamento next Wednesday by the Assembly Appropriations Committee.

Both the cap and the problem being addressed by the patient advocate proposal stem from Prop. 71, the ballot initiative that created CIRM and also wrote variety of minutia into law. The proposition requires a super-majority (65 percent) for a CIRM governing board quorum, which is based on the number of board members eligible to vote. Since many of the board members have conflicts of interest that prevent them voting on matters before the board, the presence of patient advocates is necessary to take action – much more so than many other members of the board.

A memo by James Harrison, outside counsel to the CIRM board, said,

"As a result of the requirements in Proposition 71, the Patient Advocate members of CIRM’s Governing Board are required to devote a substantial amount of time to the review of applications for research and facilities funding and the development of the standards pursuant to which research must be conducted. The time devoted to service on the Working Groups is above and beyond the time devoted to Board, subcommittee and task force meetings. In the aggregate, this service can seriously affect members’ ability to serve while simultaneously carrying out their other responsibilities, including their current occupations.

“Under the proposed bylaw, the Board would have the authority to set a daily consulting rate to compensate Patient Advocate members of the Grants Working Group and the Vice Chairs of the Facilities and Standards Working Groups for their service on the Working Groups. The Patient Advocates would continue to be limited to a per diem of approximately $116 per day for their service on the Board, Board subcommittees, and task forces. The proposed bylaw also addresses concerns that SB 1064 imposes no cap on the daily consulting rate the Board could set for Patient Advocate members of the Working Groups. Thus, it would impose a $15,000 annual cap and it would limit the daily rate to no more than 75% of the rate paid to scientific members of the Grants Working Group. In addition, the bylaw would require the Board to find that service on the Working Groups requires an extraordinary commitment of time.”

The CIRM directors' Governance Subcommittee will take up the pay plan at its meeting next Tuesday. Also on tap for the session are changes in outside contracting procedures. The agency is heavily reliant on contractors because of the 50 person staff limit.

The panel is additionally slated to discuss CIRM's grants management system, which has been a critical issue for the agency since 2007. A number of directors expressed concern at their June meeting about the staff decision to build a custom system, declaring that such efforts often have unfortunate outcomes. The staff report on the matter is not yet available to the public.

The public can take part in the subcommittee meeting at a number of teleconference locations throughout the state. The specific addresses can be found on the agenda.

Managing More than 300 Grants: CIRM's Thin Ice Question

A key panel of directors of the California stem cell agency on Tuesday will wrestle with ongoing issues involving its critical grants management system and consider changes in its policies concerning the many outside contractors CIRM is forced to rely on.

The agency has already posted some background information for the Governance Subcommittee meeting including a list of current contracts and the proposed changes in contracting. However, still missing is a report on the grants management system, which stirred strong concern from directors at their June meeting.

One director, Michael Friedman, CEO of the City of Hope, warned that CIRM was skating on “thin ice” with its plans to create its own software to monitor and track grants. Friedman said,

“Everybody has seen horrible examples of custom-designed systems that go bad.”

He continued,

“I have to express in the strongest possible terms my discomfort” with the CIRM staff decision to build a custom system.

Friedman's probing led CIRM directors to seek the report on the grants system for next week's meeting. CIRM plans to use the system for the entire grant process from application to termination. CIRM has awarded more than 300 grants involving more than $1 billion. It plans to hand out another $2 billion over the next seven years or so.

The grants management effort has a long history, dating back to 2007 when directors were told it would cost only $757,000. By our count, the agency has spent $1.2 million so far, not including staff time, with much more coming this year. CIRM has not publicly provided its own total nor has it forecast how much more will needed to be spent until the system is fully developed. Also missing are projected annual maintenance and service costs following that point.

For the current fiscal year, the CIRM budget forecasts that spending on information technology will jump by 53 percent, from $817,000 to $1.2 million, an increase of about $433,000. Most of that goes for the grant system.

Also on tap Tuesday are unspecified changes in the bylaws for the CIRM governing board.

Tuesday's meeting will have teleconference locations in San Francisco, Los Angeles, Sacramento, La Jolla, Irvine and Palo Alto. If you would like to attend any of those sessions, you should check the agenda for specific addresses. In some cases, you will need to call CIRM because it has not provided enough information on the agenda to let the public know exactly where the meetings will be held.

Jonny and His Stem Cell Breakdown

We all owe a debt of gratitude to the reader who posted an anonymous comment yesterday concerning the reality of life in stem cell labs.

The commentator poor-mouthed his brief note as “bit light.” But we think it is just what the field needs – a well-seasoned researcher engaged in educating the unwashed – sort of.

The matter involves Jonathan Garlick of Tufts. A light-hearted fellow, he is given to using an unusual method to discuss science. In this case, stem cell science.

Known as Dr. Jonny Cool J, Garlick has put together a six-minute rap on the virtues of the field. It has been viewed nearly 22,000 times.

“This Guy RULEEEES!!!” said one viewer. And now, here's Jonny.

Despite New CEO Job, Alan Lewis to Continue to Consult for CIRM

The California stem cell agency said this morning that Alan Lewis will continue to work as a consultant to the agency although he has what appears to be a full-time job as the new CEO of Ambit Biosciences of San Diego.

In the wake of the announcement of the new job, we queried CIRM earlier today about Lewis' status as the interim vice president for research and development for the $3 billion stem cell agency, an arrangement that began only on June 21.

Don Gibbons, CIRM's chief of communications, replied via a comment filed on our item that reported that Lewis had a new job. Gibbons said,

“CIRM's president was informed of Mr. Lewis' new position Friday. From the outset the $250,000 salary was to be prorated based on days actually worked with the full amount assuming a five-day week. With his new position Mr. Lewis will scale back his time with CIRM from a planned two to three days a week to 2 to 3 days a month, and the salary will be prorated accordingly, while we continue the search for a VP for R&D. “

Gibbons did not mention whether Lewis would continue to hold the title of interim vice president. Ambit and Lewis have not yet responded to our queries concerning his job with CIRM.

CIRM's New Interim VP for Research Takes Job with San Diego Firm

Only a little more than a month into his $250,000, six-month contract with CIRM, Alan Lewis has taken a job as CEO of the Ambit Biosciences of San Diego.

An anonymous reader alerted us this morning to Lewis' new post. (See the reader's comment to the left of this item under the heading “recent comments” or via the comments function on the “$250,000 Contract” item.) The reader makes the reasonable assumption that Lewis, former head of Novocell, will no longer be working part-time with the California stem cell agency. However, the full press release on Lewis' sort-of-new job does not mention the CIRM contract. We are asking both Lewis and the stem cell agency to clarify his status.

Lewis has served as executive chairman of Ambit since March, a fact not mentioned by CIRM when it announced his appointment as interim vice president of research and development. (Lewis told us that his executive chairmanship began in May. Today's Ambit news release says March.)

The anonymous reader also makes a good point concerning the amounts paid to CIRM contractors. The best talent costs money. But failing to effectively manage a $3 billion investment costs a lot more. Also readers should understand that the figures paid to independent contractors should be discounted by 35 to 50 percent if they are to be compared to conventional salaries. Standard pay figures do not include the cost of fringe benefits paid by employers, such as health insurance, retirement contributions, Social Security payments, etc. Depending on the company or government, those fringe benefits can run to 35 to 50 percent. In the case of individual contractors with CIRM, they must pay for those benefits themselves.

But regardless of the justification for spending large sums for outside contractors, California voters can be outraged by the amounts. Their reaction is visceral and emotional, a phenomena we discussed in this item. You can see examples of it on this blog on items dealing with salaries at CIRM and some outside contracts.

We also want to extend our personal thanks to the anonymous reader who brought Lewis' new job to our attention and that of our readers. We encourage comments from all readers, especially those bring fresh information to California stem cell matters.

A Matter for CIRM to Ponder: California's Visceral Reaction to High Salaries for Public Servants

Lavish government or quasi-government salaries are an anathema to California voters.

They reacted predictably with outrage last week when news surfaced about what they considered egregious greed. Jail time was urged. “Nauseating” was another word that was used.

The response is something to be considered by directors of the California stem cell agency, which has its own set of generous executive salaries. What is important here is what the voters perceive as lavish or greedy – not the perceptions of recipients or the perceptions of those who approve the pay.

One non-CIRM instance involved the city of Bell, a tiny, not particularly well-off enclave not too far south of downtown Los Angeles. It was there that the city manager resigned after it was disclosed by the Los Angeles Times that he was earning $800,000 a year. And that left him with a pension estimated at $600,000, going on $700,000. Times columnist Steve Lopez wrote,

“The sad reality, dear Californian, is that depending on where you live, you may be personally contributing to the insultingly fat pension of ousted Bell city administrator Robert "Ratso" Rizzo.”

The other instance involved the executive director of the non-profit California School Boards Association, which is based in Sacramento and supported by tax dollars that are paid to the association by school boards. The executive, who is mostly a lobbyist, retired after Sacramento television station KCRA disclosed that he made more than $540,000 two years ago, the most recent figure available.

“Piggies,” “unconscionable,” “retire him to the county jail” were some of the 129 comments filed on a Sacramento Bee story about the matter.

The salary scale at the $3 billion California stem cell agency tops out at more than $500,000. Amounts paid to its top executives have triggered harsh comments from a handful of observers. CIRM's contracts with outsiders have also been targeted. But the pay and contracts have received no widespread notice.

A good case can be made that the salaries at the highest levels of the stem cell agency are necessary and appropriate. But that makes little difference to citizens struggling with layoffs, cutbacks and wage roll backs. Even before the current dismal economic climate, they would froth and foam reflexively at what they regarded as excessive pay for public servants.

As CIRM aims at another pitch to the voters for billions more for research, its directors and executives should be preparing for a visceral and emotional outburst from citizens concerning its executives' pay.

CIRM Defends Legality of Barring Public From Marriott Meeting

The California stem cell agency says it did not violate state open meeting laws when it barred two members of the public from a meeting in June at a San Francisco hotel.

In an unsolicited note earlier this month to the California Stem Cell Report, Ian Sweedler, deputy legal counsel for CIRM, said,

“The Bagley-Keene Open Meeting Act applies to multimember boards or commissions, like the ICOC (CIRM directors) and its subcommittees, not to agency staff, or to other meetings that staff attend or organize in the operation of the agency, including the SCNT workshop.  We are always mindful of Bagley-Keene, and careful to follow it when it applies.”

We asked him to clarify his response, including whether CIRM's actions in this case violated recent changes in the California Constitution that guarantee the public a broadly construed right to information about the taxpayer's business.

Sweedler said,

“Sorry if I wasn’t clear.  Yes, I am stating, without qualification, that the SCNT workshop did not violate Bagley-Keene or Proposition 59(the change in the state Constitution), or any other law that I am aware of.  You had stated that a specific CIRM activity violated a specific law, and I thought it was important to correct that.  Thanks.”

We understand and respect Sweedler's opinion. However, it would take a court decision to determine whether he is correct. Our research indicates that a strong case can be made that such meetings must be open. Additionally, the state's open meeting laws were written well before CIRM, an agency unlike any other in state history, came into being. They must be reinterpreted not only in the wake of the Prop. 71 but also in the wake of a new, much broader constitutional guarantee of right of public access. The most important point, however, is that CIRM has pledged to go beyond the mere compliance with open meeting laws. As we noted earlier,

“Legalities aside, it is not in CIRM's best interest to bar persons from any of its sessions – not to mention that it is not in the best interests of the people of California. CIRM needs to do more than meet the minimum standards of the state's sunshine laws. To fail to do so will create a record that will surely harm CIRM's public support and hamper its efforts to secure more funding after it runs out of the $2 billion it has left to spend.”

As to whether CIRM adhered to the law, Sweedler confirmed that the meeting in question included the attendance of at least one alternate for a CIRM director, Jeannie Fontana. We also understand that some persons were in attendance who had not been invited directly by CIRM.

Those facts have an impact on whether the ban on the public is strictly legal. The First Amendment Coalition of California watches over the application of sunshine laws in California. The group says,

“California law doesn’t exactly ban deal-making by politicians in smoke-filled rooms, but it comes close to doing that at the local level (under the Brown Act) and among state agencies (under the Bagley-Keene Act). The fundamental idea behind these statutes is that the full process of political deliberating and decision-making—justly likened to the making of sausage—should be conducted in the open, in public meetings for all to see. Although the laws allow for certain matters to be considered in 'executive session,' they are the rare exception (in theory, at any rate).”

The coalition's Web site discusses cases (see here, here and here) that have application concerning the incident at the Marriott Hotel. They deal with the presence of a board member (or alternate in this case) at meetings such as those held by CIRM, as well as the possibility that they could lead to an illegal “serial meeting” of the CIRM board of directors even if only CIRM staffers were involved at the initial meeting.

In one case involving local open meeting laws, the First Amendment Coalition quoted the state attorney general as saying,

“In construing these terms, one should be mindful of the ultimate purposes of the Act — to provide the public with an opportunity to monitor and participate in decision-making processes of boards and commissions.  Conversations which advance or clarify a member’s understanding of an issue, or facilitate an agreement or compromise among members, or advance the ultimate resolution of an issue, are all examples of communications which contribute to the development of a concurrence as to action to be taken by the legislative body.”

In other words, such meetings should be open to the public.

Sweedler's statements go beyond CIRM's earlier comments. The stem cell agency previously contended that the meeting was closed to protect proprietary information, but failed to argue that open meeting laws did not apply. Don Gibbons, CIRM communications chief, said the meeting was designed “to gather information for critical decisions regarding the direction our funding should take.” To us, that sounds like something the public should have access to.

CIRM has virtually nothing to gain by barring the public. It is not as if hoards will descend on the sessions. Even full CIRM board meetings rarely attract more than 10 members of the public. Indeed, the agency is likely to benefit from comments that come from a different angle.

Correction

In two recent items, we misspelled the last name of a Duke University researcher. The correct spelling is Rob Wechsler-Reya. We had it incorrectly as Weschler.

Questions and Commentary on Stem Cell Reprogramming

The California stem cell agency and a UC Davis stem cell researcher are blogging on the implications of research that indicates that reprogrammed adult stem cells may not be the magic bullet that avoids the problems associated with human embryonic stem cells.

You can find a summary of some of the research and discussion from CIRM's Amy Adams here. Paul Knoepfler of UC Davis said,

"So if iPS cells are not that similar to ESC, what does this mean?

"First, it is not the end of the world. Many of us had assumed that iPS cells are similar to ESC in some ways, but distinct in others. These studies simply validate that notion.

"Second, iPS cells are still very useful even if they are not quite so close siblings of ESC. In fact, iPS cells do not need to be extremely similar to ESC to be useful. The pluripotency and self-renewal of iPS cells makes them a powerful tool regardless.

"Third, iPS cells are a distinct type of stem cell from ESC and should be considered as such.

"Fourth, these studies also highlight that every iPS cell line made is distinct from the others made. The heterogeneity amongst iPS cell lines is probably more substantial than the differences between ESC lines, but ESC lines also vary between each other quite a lot as well.

"Finally, the tumorigenicity of iPS cells is a serious concern. A remaining open question is how prone iPS cells are to form malignant tumors (although don't forget that teratoma can be malignant!). We predict that iPS cells are dramatically more prone to produce malignant tumors compared to ESC."

(Editor's note: An earlier version of this item contained typos in the material that was inserted from Knoepfler's original post. He corrected those typos on his blog, and we have altered his quote above to reflect those changes.)