Competing for Dollars: CIRM Examining Grant Ground Rules

The words are mind-numbingly dull: grant administration, programmatic score, appeals, pre-application. But they go to the lifeblood of scientific research – money.

And they are the topics of concern at a meeting next Wednesday of a key panel of the directors of California's $3 billion stem cell agency.

The directors' Science Subcommittee will then examine a substantial portion of the process in which directors decide which California scientists receive millions of dollars and others receive none. On the agenda are:

• Longstanding concerns about dealing with researcher appeals on applications for stem cell research grants. 
• The pre-application process, which weeds out proposals even before they get to the grant review group.
• And a new concept that would create a “programmatic” grant application score from patient advocates sitting on the grant review panel.

It is not the first time CIRM directors have tackled these sorts of issues. Directors have long been troubled by attempts to reverse negative decisions by reviewers, who examine the requests for cash behind closed doors. The directors have final say on the applications but rarely overturn reviewer decisions.

However, in June, a record nine researchers filed extraordinary petitions to reverse reviewer actions. That amounted to about one-third of the rejected grants. Four of the petitions were successful. The directors were not entirely pleased at having to deal with the renewed pitches from researchers.

Freshly before CIRM directors is the concept of a programmatic score on applications in addition to the scientific score. The new score would be provided by the seven patient advocates on the 23-member grant review group.

CIRM directors sometimes refers to programmatic considerations in approving grants. The term is usually used in connection with the programs that the agency is trying to push. A specific definition of the term may exist on the CIRM Web site, but we have not been able to find it.

In response to a query, Jeff Sheehy, a patient advocate member of the board and chair of the Science Subcommittee, said the programmatic score proposal is only an idea at this point. No details have been worked out, which is the task of the subcommittee and staff. Noting that the concept did not originate with him, he said he did not expect the panel to act on the item at the meeting.

Sheehy, who also serves on the grant review group, said,

“There is no programmatic score right now. Grants receive a numerical scientific score, which is the average of the individual scores of the 15 scientist members of the Grants Working(review) Group.

“During programmatic review, a baseline 'quality' score is established, usually somewhere around 70. Then the group decides whether to move grants up or down based on programmatic considerations, which vary from RFA to RFA--although they are often based on disease representation. For example, zero Alzheimer's applications in the fundable range could lead to a motion to move an Alzheimer application up (usually this happens for application with a near fundable score) into the recommended for funding category.”

We have written more than once on the appeals and pre-application issues and have prepared a reading list for those who really want to dig into them. You can find the list here.

Persons interested in commenting on the proposals can email their comments to CIRM at info@cirm.ca.gov. Or they can listen in and comment live during the meeting at seven locations throughout California, including San Francisco, Palo Alto, Healdsburg, Pleasanton, Duarte and two in Irvine. You can find the specific locations on the meeting agenda.
.

CSCR Reading List: Grant Appeals at the California Stem Cell Agency

Here is a list of articles from the California Stem Cell Report and CIRM documents dealing with the grant appeal process at the California stem cell agency. The list was prepared on Sept. 20, 2010. To read the entire articles, click on the links.

Articles from the California Stem Cell Report

Aug. 10, 2010
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.

July 19, 2010
UC Davis Scientist Praises CIRM Appeals Change
A stem cell researcher at UC Davis today said a change in the CIRM grant appeals procedure makes “a lot of sense.” Writing on his blog in regard to "extraordinary petitions," Paul Knoepfler said, “I think the proposed change makes a lot of sense and would greatly improve the process. Sometimes the reasons in the petitions are clearly not meritorious and as it now stands, they end up wasting CIRM's time. The last time CIRM received 9 petitions as well, which represented a remarkably large fraction of the total applications. A stricter process would discourage the submission of large numbers of petitions, an important issue given that the number of petitions received by CIRM continues to grow.”

CIRM Finally Discloses Grant Appeal Proposals
The California stem cell agency early today belatedly posted a two-page memo on proposed changes in how it will deal with appeals by scientists whose grant applications have been rejected by reviewers.

July 18, 2010
Sticky, Troubling Appeals by Rejected Researchers Targeted by Stem Cell Agency
A key step in the process for awarding billions of dollars in research grants is “broken,” according to many directors of the California stem cell agency, and major changes are looming that will affect hundreds of scientists.

June 22, 2010
Immunology Grants: CIRM Gives $25 Million to 19 Researchers
Directors of the California stem cell agency today approved $25 million for immunology research, overturning four negative decisions by its grant reviewers. Directors faced a record nine public petitions to reverse its reviewers. After some grumbling, the directors, who see only a summary of the application and reviewer comments, okayed the four.

June 19, 2010
More Grant Appeals Filed: Yamanaka Invoked
The California stem cell agency has set another benchmark, although this is one that it may not want to trot out at international stem cell gatherings. Eight scientists whose applications were rejected for funding by the CIRM grants working group and scientific reviewers are seeking to overturn those decisions at the agency's board meeting in San Diego on Tuesday. It is the largest number of “extraordinary petitions” ever filed and amounts to more than one out of every four applications that were turned down. The total number of applications received was 44. Fifteen were approved. Some of the researchers are likely to appear at the board meeting and make a personal pitch.

May 18, 2010
Competing for California Stem Cell Cash: Rules of the Game Coming Under Scrutiny
Every California stem cell scientist and researcher looking to join the field – be they from academia or business – should pay very close attention to a meeting next week of a key group of directors of the $3 billion California stem cell agency. They plan to discuss possible changes in how scientists compete for stem cell cash, which is no small matter since CIRM has another $2 billion to hand out over the next several years.

CIRM documents

Pre-application review – CIRM report (Jan. 2010) on the process

Extraordinary petition policy – Version as of 5/25/10

Appeal policy – Version as of 5/25/2010

Transcript of July 20, 2010, meeting of CIRM directors Science Subcommittee. Discussion of petitions begins on page 40.

Transcript of the June 22, 2010, CIRM directors meeting. Discussions of extraordinary petitions begin on pages 24 and 67.

Transcript of 5/25/10 Science Subcommittee meeting dealing with appeals issue. Discussion begins on page 99.

Northwestern Is Lead Site for Geron hESC Trial

Northwestern this afternoon confirmed that it is the first site to be ready to accept candidates for hESC clinical trials with Geron, Inc., of Menlo Park, Ca. The Illinois organization is also the lead site for the unprecedented trial.

Northwestern's role surfaced during the weekend in a case involving a severely injured California jockey. See here and here.

Here is Northwestern's press release, which is not yet on its Web site. (The item subsequently was posted here.)

NORTHWESTERN FIRST SITE OPEN FOR SPINAL CORD STEM CELL TRIAL

Northwestern Medicine and RIC ready to enroll first subject in spinal cord injury study

CHICAGO --- Northwestern Medicine is the first site open for enrollment in a national clinical research trial of a human embryonic stem cell-based therapy for participants with a subacute thoracic spinal cord injury. Following the procedure, participants will receive rehabilitation treatment at The Rehabilitation Institute of Chicago (RIC).

Northwestern also is the lead site of the trial, sponsored by Geron Corporation (Nasdaq: GERN). The trial eventually will include up to six other sites and enroll up to 10 participants nationally.

“We are very pleased to be the first participating center in the world’s first human embryonic stem cell clinical trial for spinal cord injury,” said lead national investigator Richard Fessler, M.D., professor of neurological surgery at Northwestern University Feinberg School of Medicine and a surgeon at Northwestern Memorial Hospital.

“Injection of oligodendrocyte progenitor cells directly into the spinal cord lesion is a rational way to attempt to arrest or reverse the structural damage in the spinal cord caused by severe trauma,” Fessler said. “We are eager to begin evaluating the effects of these cells in subjects with severe spinal cord injuries.”

“RIC is a vital member of the research team for this novel stem cell clinical trial,” said David Chen, M.D., medical director of the RIC Spinal Cord Injury Rehabilitation Program. “RIC’s team of spinal cord injury rehabilitation specialists is responsible for customizing the rehabilitation care plan and therapeutic intervention for each participant, which may include robotic walking therapy and other procedures to facilitate the participant’s neurologic repair and recovery. At RIC, restoring the participant’s ability is our objective and the scientific application of embryonic stem cells offers new hope for recovery.”

The primary objective of the phase I trial is to assess the safety and tolerability of special cells called human embryonic stem cell-derived oligodendrocyte progenitor cells when they are injected into the spinal cord injury of paralyzed subjects. The injuries have to have occurred within two weeks for someone to be eligible for the procedure.

In addition to evaluating safety, the secondary aim of the trial is to see if the stem cells improve neuromuscular control or sensation in the trunk or lower extremities.

In previous animal studies, these stem cells have demonstrated the ability to remyelinate or recoat damaged nerve cells that have lost their ability to conduct electrical impulses down the axon. The stem cells also have shown nerve-growth stimulating properties leading to restoration of function in animal models of acute spinal cord injury.

“The trial is supported by positive animal research,” Fessler said. He noted the trial is using the lowest dose possible for a human based on the animal studies.

Subjects eligible for the Phase I trial will have documented evidence of functionally complete (ASIA Impairment Scale grade A) spinal cord injury with a neurological level of T3 to T10 spinal segments and agree to have GRNOPC1 injected into the lesion sites between 7 and 14 days after injury.  For more information, go to information pages of Geron’s website at www.geron.com.

Clinical Trial Challenges: The Matter of Michael Martinez

The complexities of finding candidates for clinical trials as ground-breaking as the hESC effort by Geron were touched upon indirectly in news coverage of the case of jockey Michael Martinez.

This morning the San Francisco Chronicle noted that the state workers' compensation department played a negative role in the matter. Earlier, the Daily Racing Form reported that Highland Hospital in Oakland, Ca., initially refused to release Martinez' records because he could not give consent.

Here is what reporter Larry Stumes wrote this morning:

"The decision by Dr. Richard Fessler of Northwestern University came late Monday after a tumultuous day in which Martinez was to be transferred from Highland Hospital in Oakland to UCSF for a high-resolution MRI exam. The transfer was canceled when the state Division of Workers' Compensation refused to authorize it.

"'The doctors at Highland weren't entirely in favor of the transfer and in an e-mail to Dr. Fessler they indicated that they thought that Michael was doubtful as a candidate for the embryonic stem-cell treatments,' said Golden Gate Fields physician Dr. David Seftel, who is advising Martinez's family on his care. 'The family is devastated, but we're regrouping. I don't give up; Michael doesn't give up.'

"Seftel has contacted Dr. Jorge Paz Rodriguez, the medical director of the Stem Cell Institute of Panama - Martinez's native country - regarding adult stem-cell therapy.

"'The benefits of adult stem-cell treatments have been relatively modest, confined to improvement in sensation, bladder control and bowel control,' Seftel said. 'But because it is so soon after the injury, it is possible Michael could get some of his motor control back. The sooner we get him to Panama, the better.'"

Here is what Chuck Dybdal of the Racing Form wrote.

"After initially refusing to release Martinez’s records so that Northwestern University’s physicians could review them, Highland Hospital agreed late Friday to release them. Highland had cited laws that prohibit the release of the records to anyone but Martinez, who has been rendered incapable of responding to specific requests because of the nature of his injuries."

Embryonic Stem Cell Treatment Ruled Out for California Jockey

California jockey Michael Martinez, whose spine was severely damaged earlier this month, will not be enrolled in Geron's clincal trials for hESC treatment, the only such in the nation.

Reporter Matt Hegarty of the Daily Racing Form wrote this afternoon,

“Specialists at Northwestern University near Chicago have decided that the rider Michael Martinez is not a candidate for a clinical trial using embryonic stem cells to treat spinal-cord injuries, according to the track physician at Golden Gate Fields, where Martinez was severely injured in a fall on Sept. 12.

“Dr. David Seftel, the physician, said that the neurosurgeons conducting the trial had concluded from Martinez’s medical records that the jockey’s spinal cord had been too severely damaged to consider Martinez for the trial. Seftel and Martinez’s family had hoped that the treatments, which have shown some promise in studies on rats, would be able to mend the rider’s severed spinal cord. Martinez is paralyzed from the waist down.

“The family received the news that Martinez would not be admitted to the trial on the same day that Martinez’s fiancé, Charlotte, went into labor and was admitted to Highland General Hospital(in Oakland, Ca.), where Martinez is currently receiving treatment. The baby was expected to be delivered later on Tuesday, Seftel said.

"'It’s a day of extremely mixed emotions,' Seftel said."

The New York Daily News on Sunday carried a lengthy story on the accident, in which an 1,100-pound horse running at 35 miles an hour fell on Martinez. The story by Christian Red discussed Geron's involvement.

He wrote,

“The Menlo Park, Calif.-based biotechnology company Geron, which has been approved to conduct clinical trials of stem cell treatment on humans, after the Food and Drug Administration lifted the hold on the company's Investigational New Drug application July 30, would possibly conduct the treatment.” 

Red continued,

“But Martinez is in a race against time, even if he is eligible to get the treatment. According to Dr. Ed Wirth, the medical director of regenerative medicine at Geron, 'stem cells need to be injected between seven and 14 days after the spinal cord injury because that's the time window in which we've seen the best chance of benefit in the animal studies.'

“Geron plans to have seven facilities around the country opened to carry out these trials, and although the company has not made a public announcement, Seftel said that one of the facilities at Northwestern Universityin Evanston, Ill., is currently set up to receive applications for candidates.”

The Racing Form's story this afternoon said,

“Martinez is expected to be transferred late on Wednesday to Santa Clara Valley Medical Center, which runs a rehabilitation clinic that specializes in spinal-cord injuries. Seftel and Martinez’s cousin, the rider Alex Solis, are also exploring experimental treatments with adult stem cells, though, in studies, those treatments have not shown to be as promising as the embryonic stem-cell treatments, Seftel said.”

More Info on hESC Treatment of Jockey with Severed Spinal Cord

Benoit & Associates

Jockey Michael Martinez (left), with cousin Alex Solis.

More details are emerging on the possible use of experimental hESC treatments within the next two weeks on a California jockey with a severed spinal cord.

According to an article yesterday by Chuck Dybdal in the Daily Racing Form, which appears to have carried the first account of the possible treatment, it involves neurological specialists at Northwestern University, presumably at the Acute Spinal Cord Injury Center at Northwest Memorial Hospital.

(Subsequently, it appears that the first story may have been in the New York Daily News on Sunday.)

The center is a nationally recognized leader in spinal cord injury treatment, one of only 14 model systems in the country for spinal cord injury treatment. The center's Web site says it is involved in using stem cells to repair damaged spinal cord and is aggressive in placing patients in innovative rehabilitation programs.

Richard Fessler, a professor of neurological surgery at Northwestern, is evaluating the jockey's MRIs, which are being taken at UC San Francisco, according to a story on page B6 of the sports section of the San Francisco Chronicle.

Neither the story in the Racing Form or in the Chronicle mentions whether treatment involves Geron, Inc., of Menlo Park, Ca., which is conducting the only hESC clinical trial in the country.

In response to a query, Anna Krassowska, a spokeswoman for Geron, told the California Stem Cell Report,

“As you know, there is no other hESC-based therapy cleared for clinical
trials. However, I can't shed any light on this story.”

We also have queried Northwestern and Fessler concerning the possible treatment of the jockey.

The Racing Form story said,

“(Jockey Michael) Martinez suffered a severed spinal cord in a Sept. 12 racing accident at Golden Gate Fields. He needs the MRI to determine if there is enough white matter – a component of the central nervous system that carries messages to and from the brain – for the stem cells to have a chance to work in the experimental treatments, according to Golden Gate Fields track physician Dr. David Seftel.”

Dybdal also wrote,

“After initially refusing to release Martinez’s records so that Northwestern University’s physicians could review them, Highland Hospital agreed late Friday to release them. Highland had cited laws that prohibit the release of the records to anyone but Martinez, who has been rendered incapable of responding to specific requests because of the nature of his injuries.

“A hearing was to be conducted Monday in an Alameda County court as Martinez’s parents, who have come to the United States from Panama, seek to become their son’s temporary conservators for health-related issues. If they are named conservators, Martinez’s parents could approve the experimental stem-cell treatments for their son.

“Martinez has shown continued progress from his injuries, Seftel said. He is able to eat soft foods and drink. All IVs except one have been removed.

“'He’s looking better and shows continual neurological improvement,' said Seftel.

“Seftel said the improvement in his condition would allow Martinez to be flown to Chicago on a private jet with a doctor and nurse in attendance, but that he would not need a specially equipped Medi-Vac flight.”

Chronicle Reports Possible hESC Treatment of Severed Spinal Cord

The sports section of the San Francisco Chronicle carried an intriguing but brief story this morning dealing with use of embryonic stem cells to “repair” the severed spinal cord of an injured jockey.

The story by Larry Stumes said Michael Martinez is in the UCSF medical center for an MRI exam to determine whether he will be flown to Chicago this week to determine whether he is a candidate for the experimental treatment.

A number of unanswered questions are implicit in the story. We are contacting various parties to find some answers.

CIRM Leads National Effort to Forge 'Pathways' with FDA

California's $3 billion stem cell agency has created a broad-based, 43-member, interstate consortium of researchers and businesses to work with the FDA to develop “well-defined regulatory pathways for stem cell therapies.”

CIRM President Alan Trounson is high on the effort, which will be making another quasi-public appearance in just a few days. Last spring, Trounson told CIRM directors that he is “thrilled” with the initiative, which is spearheaded by CIRM General Counsel Elona Baum.

The next consortium program comes up on Sept. 28 – a “webinar” on preclinical considerations for stem cell therapies. The session, which requires advance registration, will feature Mercedes Serabian, chief of a key pharmacology/toxicology branch in the FDA; Robert Deans, senior vice president of Athersys, Inc., of Cleveland, Ohio, and Melissa Carpenter, a stem cell industry consultant and formerly with Geron of Menlo Park, Ca., StemCells, Inc.,of Palo Alto, Ca., and Novocell(now ViaCyte) of San Diego.

Baum has already conducted one webinar on issues on product characterization, which is now available for viewing on the CIRM Web site along with additional materials. Trounson said Baum “has been fantastic in getting the FDA along.”  Trounson told CIRM directors in April,

“If you were able to take the time to listen to these webinars, they're terrific. The information that's coming from the FDA and from the scientists is very, very helpful. And it's a learning process that's going both ways.”

The 43 members of the consortium include George Daley of Harvard, Irv Weissman of Stanford, Owen Witte of UCLA, Tom Okarma, CEO of Geron; Ed Field, president of Aldagen, Inc., of Durham, NC; John West, president of ViaCyte, Inc., of San Diego; William Caldwell of Advanced Cell Technology of Santa Monica, Ca.; Randy Mills, president of Osiris Therapeutics, Inc.,of Columbia, Md., and executives from Pfizer, Johnson & Johnson, iPierian of South San Francisco, Ca.; Genzyme of Cambridge, Mass., and the WiCell Research Institute of Madison, Wi., among others.

On its CIRM-based Web site, the consortium said that the stem cell field will move “faster when interested parties share best practices and resources.” The consortium said,

“This group provides a forum for members to discuss amongst themselves or with the FDA issues of importance to the industry. The RMC's mission also includes serving as a technical resource during development of guidelines and standards.”

The consortium Internet site contains a wide range of links to FDA, ISSCR and other materials. In addition to the Sept. 28 webinar, the consortium has a link to a Nov. 2 FDA workshop on cell and gene therapy trials.

CIRM Salaries: More Than You Want to Know

Salaries at the California stem cell agency tend to be generous when compared to most other state agencies and have triggered comments from some that they are, in fact, “outrageous.”

However, in 2009 the salary of CIRM President Alan Trounson was only $490,182.97, well below the $2.3 million for the head football coach, Jeff Tedford, at the Berkeley campus of the University of California. Tedford earned the most of any of California's public servants that year. No. 2 was another UC coach. No. 3 was an academic with $1.9 million. He is Timothy H. McCalmont, a professor of clinical pathology and dermatology at UC San Francisco.

Nonetheless, Trounson, Tedford and McCalmont all share one common characteristic. Their salaries are of a magnitude that makes California voters gasp and shudder. They have a visceral, negative reaction to what they regard as excessive wages for government employees – a reaction that is not necessarily perfectly rational.

The governor, who makes $212,179, and state lawmakers, who make $116,208, effectively can do nothing to change CIRM salaries. Prop. 71, which created the stem cell agency, walled it off from mischievous fingers that might want to meddle.

Currently CIRM's executive salaries are below the radar of both public and news media. But CIRM is considering proposing, as soon as two years from now, another multibillion dollar ballot measure to extend the existence of the stem cell research effort. That could raise significantly the attention level of the salaries.

Interestingly, the agency partly justifies its salaries on the basis that the agency could go out of business as soon as 2015 when it may run out of its original $3 billion. However, an additional $4 billion bond measure could prolong its life for another 10 years or more.

We have written from time to time about salary issues at CIRM. The agency itself has a number of pertinent documents. But dredging up all the relevant material can be laborious. To help readers navigate the salary information, we have prepared a reading list of stem cell agency documents, a state salary database and selected articles from the California Stem Cell Report. More items can be found on this web site by searching on the term “salaries.”

We will be preparing more reading lists on California stem cell topics. If you would like to see a reading list on a particular subject, please send a note along to djensen@californiastemcellreport.com. Or you can simply make a request via the “comment” function at the end of this item. Just click on the word “comment.”

The salaries reading list can be found here and here.

CSCR Reading List: Salaries at the California Stem Cell Agency

Here are links to articles and California stem cell agency documents dealing with CIRM salaries, which are high compared to many state agencies and which have come under fire from time to time.

CIRM salary ranges

Searchable Sacramento Bee database on salaries of all state employees, including the University of California and the California state university system

CIRM compensation policy

CIRM compensation philosophy
This document attempts to make the case for the high salaries that exist at CIRM at some levels. Among other things, the agency says,

“CIRM employees must be intelligent, entrepreneurial, motivated, flexible, confident in their own abilities, and committed to stem cell science. To retain this special level of employee, CIRM’s employment policy must reflect and reward the uniqueness of a CIRM employee.”

It also says,

“CIRM’s anticipated life-span is 10-14 years, which rules out the possibility of a long-term career track that is available for many civil service positions in the UC system.”

Here are California Stem Cell Report articles dealing with compensation. Others have been published and can be found by searching on the term “salaries” on this web site.

A Matter for CIRM to Ponder: California's Visceral Reaction to High Salaries for Public Servants, July 25, 2010

Science vs. Salaries: What Do People Talk About? Dec. 14, 2009

Stem Cell PR, Salaries and Mixed Messages, Dec. 10, 2009

New CIRM Figures Show 25 Percent Budget Increase, June 17, 2009

“The largest component of the budget goes for salaries and benefits, which are projected at $7.4 million for 47 employees. That is $1.9 million more than this year's estimated figure of $5.5 million. Personnel costs next year amount to an average of roughly $150,000 in salaries and benefits for each CIRM employee.”

CIRM Executive Salaries Take a Hit, April 9, 2008

"Should the president of the California stem cell agency, with roughly 26 employees, be paid $300,000 more annually than the director of the National Institutes of Health, which has nearly 19,000 staffers?"

Legal Wheels Turn: Ban on hESC Funding Temporarily Removed

The nation's stem cell scientists received a reprieve today, courtesy of a federal appellate court that put a hold on an earlier order to halt federal funding of hESC research.

Gardiner Harris of the New York Times wrote:

"The appeals court ruling could save research mice from being euthanized, cells in petri dishes from starving and scores of scientists from facing a suspension of paychecks, according to arguments the Obama administration made in the case. It could also allow the National Institutes of Health to provide $78 million to 44 scientists whose research the agency had previously agreed to finance."

Rob Stein and Spencer S. Hsu of the Washington Post wrote:

"(T)he appeals court made it clear it was not making a final decision about the case, which means the reprieve could be short-lived and the fate of the funding could continue to be whiplashed by seesawing court rulings."

The next court action is not expected to come until sometime after Sept. 20, the deadline for filing additional arguments in the case.

The legal brouhaha makes clear several facts concerning research funding. If you are a scientist, your research is not secure unless you are paying for it yourself. NIH funding is subject to the vagaries of the courts and Congress. Private funding comes with its own set of strings, which generally are not revealed to the public, but they are there. And despite the assurances of the California stem cell agency, its funding can be threatened under some circumstances, as we saw in 2009. CIRM's resources are clearly subject to the state's ability or desire to borrow money and issue the state bonds that are the agency's only real source of cash.

Time to Let Lawmakers Know What They Need to Do

A UC Davis stem cell researcher has joined in the campaign to change the law that resulted in the court order temporarily halting federal funding for human embryonic stem cell research. He is looking for more than a few good supporters.

Paul Knoepfler has posted on his blog a tool that makes it easy for others to join him and write their Washington representatives seeking immediate repeal of the law. It allows readers in any state to look up their elected officials and let them know what needs to be done.

Knoepfler and Don Reed, a longtime patient advocate in California, should get together. Reed also has a blog in which he seeks to create a stem-cell friendly environment nationally and in California. Reed has not yet posted a similar pitch but may well do so.

Reed has been lobbying elected officials for years. His efforts were key to passage in California of a 1990 measure that funded research linked to Geron's spinal cord clinical trials.

That law, however, is in danger of fading from the books. The law is named after his son, Roman, who was paralyzed some years ago in a football accident. Roman also has lobbied for stem cell support and came up with the slogan of the California stem cell agency – “Turning stem cells into cures.”

On his blog, the elder Reed is appealing for folks to write the governor supporting the legislation, which is now on his desk.

Reed writes,

"This law paid for the first state-funded embryonic stem cell research in America, re-insulating damaged spinal nerves. Laboratory rats so badly paralyzed they could only drag themselves are scampering now; that study goes to human trials with Geron. The same research may help cure spinal muscular atrophy, (SMA, a vicious condition which kills children, often before the age of two), multiple sclerosis (MS), and other disorders.

"'Roman’s Law' has helped train new scientists with fellowship grants, and assisted veterans to develop new approaches, from a variation of the petri dish to pioneering new methods of rehabilitation and repair. In addition to 175 published scientific papers, two patents pending which may advance the biomedical industry, and several major scientific breakthroughs, our research brought new money to California."

CIRM Moves Ahead on $50 Million Clinical Trial Round

The California stem cell agency has posted its much-delayed RFA for its first foray into clinical trials – a $50 million loan/grant round that is predicted to have only three applicants.

Firms mentioned publicly as likely to seek the CIRM funds include Geron of Menlo Park, Ca.; Ipierian of South San Francisco, and Advanced Cell Technology of Santa Monica, Ca. The RFA calls for companies to receive loans of up to $25 million each if their applications are approved. Nonprofits would receive grants. CIRM said it only expects to make one or two awards, although the CIRM board could change that.

The RFA, which went up on the CIRM Web site on Aug. 24, originally was scheduled to be posted in April or May. CIRM, which touts its openness and transparency, has not responded to multiple inquiries over several months about the reasons for the delay.

The RFA calls for a successful applicant to have an approved IND, but not necessarily at the time of the review of the applications. CIRM could have delayed the RFA to give potential applicants to time to have one in the pipeline. The RFA said,

"The award recipient must have an IND that is in effect (i.e. not subject to clinical hold) for the novel cell therapy proposed for CIRM funding before issuance of notice of award.” That notice is provided by staff well after approval of an award by the board and could also possibly be delayed pending a go-ahead on an IND."

CIRM does not expect to fully fund a clinical trial, only take part in the financing. It also cannot, by law, fund activities outside of California.

The clinical trial round is part of CIRM's aggressive push to produce results that will encourage voters to approve another multibillion dollar bond measure to continue financing stem cell research with money that the state borrows.

The clinical trial RFA gives CIRM President Alan Trounson special authority to “permit exceptions to requirements specified in this section V.(eligibility) of the RFA (except for the requirement for a cell therapy derived from human pluripotent stem cells) if the president determines, in his sole discretion, that the applicant has demonstrated that the exception would preserve an important research opportunity or make a critical contribution to one of CIRM’s mission objectives.”

The RFA said the exeception requests must be filed by Sept. 29. Letters of intent are also due Sept. 29 with board approval of awards sometime next summer.

Legislation to Give CIRM More Employees Goes to Governor

Legislation to remove the 50 person cap on the size of the staff of the California stem cell agency won final legislative approval yesterday.

The measure, SB 1064 by Sen. Elaine Kontaminas Alquist, D-San Jose, is now on its way to the governor's desk where it is expected to be signed. The bill would go into effect at the beginning of the year.

The limit on the number of employees was written into law by the ballot initiative, Prop. 71, that created the $3 billion research effort. The cap was redundant since the agency has a legal limit on operational expenses. The restriction ultimately hampered the agency's ability to perform its work.

In addition to removing the staffing cap, the compromise bill would require performance audits, albeit limited, of CIRM beginning next year at the agency's expense, according to the latest state Senate analysis of the measure. It also allows the agency to pay the patient advocates who serve on its board up to $15,000 a year. The CIRM board has already acted to do so.

CIRM backed the bill after it was significantly watered down. Gone are many reforms recommended by the Little Hoover Commission, the state's good government agency, along with provisions sought by the state's top fiscal officer, Controller John Chiang.

They include elimination of a performance audit by a special, Prop. 71-created, financial oversight committee chaired by Chiang. Instead CIRM itself would pay ($400,000 plus) for the audit and control its scope. CIRM already has written into the bill a stipulation that the audit does not have to include “a review of scientific performance.”

The staff analysis of the bill that was presented yesterday when it cleared the Senate floor on a 35-0 vote said,

“The author's office states that, while stem cell research is an important and laudable goal, concerns about transparency, accountability and oversight raised by the public, the independent Citizen's Financial Accountability Oversight Committee, the Little Hoover Commission, and the state controller detract from CIRM's ability to provide grants and loans in the most efficient way.

“These concerns divert resources and attention from CIRM's ability to maximize voter's investment in stem cell sciences. In 2009 alone, CIRM spent $1.5 million in external contracts for legal services, lobbying, public relations and communications costs to improve its public image, which is a duplication of existing internal resources. Given that the debt from the bonds is serviced from the (state's) general fund, concern about CIRM's lack of transparency and accountability gains greater significance during these challenging fiscal times. By addressing many of these public concerns, this bill enhances CIRM's ability to make grants and loans, and the removal of such barriers frees up resources that were previously diverted from the grant and loan programs.”

According to the analysis, the CIRM performance audits would cover “programs, functions, operations, management systems, and policies and procedures to assess whether it is achieving economy, efficiency, and effectiveness in the employment of available resources.”

The analysis also said it would be at least 10 years before CIRM is likely to generate revenue for the state through the results of the research it finances. The analysis said,

“Due to the time it takes research to be done and a product to be commercialized, the general fund is unlikely to see significant revenue until about 2020. The amount of revenues is unknown and depends on the number and types of drugs and technologies that are commercialized as well as their commercial success.”

CIRM's Sheehy Says CIRM to Pay Off in Cures and Economic Development

On Sunday, we carried an item dealing with the political environment in California surrounding a possible additional $4 billion bond measure to continue financing the California stem cell agency.

CIRM Director Jeff Sheehy, chairman of the board's Scientific Subcommittee, longtime patient advocate and communications manager at UC San Francisco, sent along the following response. It was received before the federal court ruling on hESC research, which Sheehy could have added as a reason for CIRM support.

“I think, David, you are looking at this as a game of 'zero sum' economics in which you assume every dollar spent on stem cell research is a dollar lost to some other worthy state budget item.

“The reason states issue general obligation bonds is that economists recognize that certain investments (historically in physical infrastructure like roads, bridges, ports, and school and university buildings for instance) create value that returns more than to the cost of the investment back to the state. Not only does building a bridge or road hire and pay companies and workers who then pay state income taxes and sales taxes, but there is a multiplier effect by which their personal spending of their wages, etc., on other items circulates through the economy creating additional spending. Further, the new bridge or road speeds other Californians to work faster and more efficiently saving hours of productive time that would have been spent in traffic, creating additional value. Ambulances or fire trucks get to emergencies faster saving lives or property. Given that some investments produce more money for the state in the long run than the money initially invested, states routinely issue government obligation bonds rather than try to budget this funding out of annual general fund dollars. The revenue from the increased economic activity deriving from the investment more than covers the bond repayments that come out of the general funds.

“The more salient question for CIRM is whether it is actually building a platform for the creation of future wealth or building a 'bridge to nowhere' that does little to increase the productive capacity of California. And the Institute of Medicine report, if it is to have any value, must answer that very question. Are the investments in the dozen new facilities for stem cell research, the training of new scientists and technicians from the undergraduate level through the post-doc level, and stem cell research from the basic, laboratory level on through to the clinic creating a platform by which additional wealth for California will be created far beyond the repayment costs of the bonds?

“And while I need a solid IOM report to definitively answer the question, I do believe that overall (minus a lot of superfluous contracts and overly high salaries and a cavalier attitude towards ensuring value for the taxpayers by many CIRM staffers) the investments in intellectual infrastructure made through Prop. 71 will pay off hugely for California as it leads the world in developing and deploying regenerative medicine.

“If CIRM does nothing else but functionally cure HIV infection as the LA Times article suggests is possible, the savings for the state will be huge in lowered medical costs and in income for the state from profits and the growth of Sangamo, based in Richmond CA. This approach targeting HIV may not work, but I feel strongly that eventually some cure for some disease or condition will come out of this spending.

“I also think companies will form and grow just like Intel, Apple, Google and eBay did from the investments made in research at California universities and institutes. Genentech and Gilead are both biotech giants that emerged from research done at California institutions that are generating substantial dollars in economic activity and creating jobs and tax revenue for the state. iPerian, forming and locating here thanks to CIRM and mentioned by you in an earlier column, might be a wealth generator like those mentioned above or it could be one or more of the many small biotech firms working in regenerative medicine up and down the state.

“So David, while I always greatly appreciate your commentary and your reporting, I think to put CIRM funding in the same barrel as annual general fund financing for schools is off the mark. With a five-year-old in public school in San Francisco, I am as frustrated with Sacramento¹s inability to adequately and consistently provide funding on an ongoing basis to educate our children as anyone could be. But pitting annual school funding against capital investments for our future will not stimulate the types of debate that will lead to answers for the respective, relevant questions.”

California Radio Talk Show on hESC Ruling

Art Torres, co-vice chairman of the California stem cell agency, will be one of the guests on a radio talk show tomorrow at 9 a.m. PDT on station KQED in San Francisco dealing with this week's hESC ruling. You can listen to the program live on the Internet.

The station said,

“National Institutes of Health director Francis Collins said Tuesday that the recent court ruling blocking federally funded research on human embryonic stem cells won't affect grant payments that have already been paid out this year. But the institute will freeze its reviews of new grants of this type. Although California's $3 billion stem cell initiative is not affected, we talk about the ruling and its potential impact on Bay Area biotech. Guests include, Dr. David Stevens, chief executive officer of Christian Medical and Dental Associations; Dr. Helen Blau, professor and director of Baxter Laboratory for Stem Cell Biology at Stanford University; Tom Abate, staff writer covering economics for San Francisco Chronicle; and Art Torres, former chairman of the California Democratic Party and vice chair for the board at California Institute for Regenerative Medicine.”

The Latest from the NIH re the hESC Ruling

UC Davis stem cell research Paul Knoepfler this afternoon reported on the latest from the NIH on the federal court ruling on hESC research.

Writing on his blog, he quoted the text of the statement and then offered a comment.

“Pursuant to a court order issued August 23, 2010, NIH is not accepting submissions of information about human embryonic stem cell lines for NIH review. All review of human embryonic stem cell lines under the NIH Guidelines is suspended. The February 23, 2010, proposal to revise the Guidelines is also suspended.

“My interpretation of this is that basically all the changes to embryonic stem cell policy under the Obama administration and all the federally funded use of ES cell lines approved under the new guidelines during this administration is suspended. No one should bother submitting new lines for approval and those that were under review are not going to be reviewed any more. All of that is frozen.”

Media Coverage: Political and Research Implications of hESC Ruling

Here are some excerpts and links to interesting coverage of yesterday's federal court ruling on stem cell research.

Text of the judge's ruling from the Washington Post.

Wall Street Journal, reporters Laura Meckler, Gautam Naik and Brent Kendall on election year politics and more.

"It also could inject the divisive issue into election-year politics and spark discussion in Congress whether to try to nullify the decision by writing new legislation.... 

"The government is spending about $137 million on human embryonic stem cell research this year and is projected to spend about $126 million next year. It's unclear whether the judge's decision would affect currently funded projects. Stem-cell advocates were calling on the government to appeal the decision and seek to have the preliminary injunction nullified....

"A significant amount of stem-cell research will go forward thanks to private funding and the state of California's ambitious stem-cell initiative, which isn't affected by Judge Lamberth's ruling. The California group (CIRM) spends $250 million annually on stem-cell research, with some 30%-40% of the money directed to embryonic stem-cell research."

Los Angeles Times, reporters Karen Kaplan and Naom Levy, on legal view of ruling.

"UCLA law professor Russell Korobkin, an expert on stem cell legal issues, said the ruling was "a terrible decision."

“By considering all research part of an unbreakable continuum, the decision implies that the Dickey-Wicker Amendment has no limits, which is an unconvincing interpretation, Korobkin said. 'It suggests that by conducting research on an acorn a scientist would also be conducting research on an oak tree, because acorns come from oak trees,' he said.”

New York Times, reporter Gardiner Harris, on feeding stem cells and politics of the decision.

"'I have had to tell everyone in my lab that when they feed their cells tomorrow morning, they better use media that has not been funded by the federal government,' said Dr. George Q. Daley, director of the stem cell transplantation program at Children’s Hospital Boston, referring to food given cells. 'This ruling means an immediate disruption of dozens of labs doing this work since the Obama Administration made its order.'

“In his ruling, Chief Judge Royce C. Lamberth of the U.S. District Court for the District of Columbia wrote that his temporary injunction returns federal policy to the “status quo,” but few officials, scientists or lawyers in the case were sure Monday night what that meant. Dr. Daley was among those who said they believed that it meant that work funded under the new rules had to stop immediately; others said that it meant that the health institutes had to use Bush Administration rules to fund future grants....

“The ruling could prove politically tricky, since it returns to public attention the politically divisive issue of abortion and research politics. President Obama made support for the research a signature part of his campaign, and he over-turned the Bush Administration’s more restrictive policy in the first two months of his administration.

“Polls show that the public generally supports embryonic stem cell research, and Judge Lamberth’s ruling — while a surprising legal setback for one of the administration’s signature scientific policies — could prove politically beneficial for the administration by reminding votes of a popular decision.”

CIRM still open for business -- Ron Leuty, San Francisco Business Times, The Associated Press(AP story appeared in The Sacramento Bee, San Diego Union-Tribune and other papers)

Washington Post story, reporters Rob Stein and Spencer Hsu

"'This is devastating, absolutely devastating,' said Amy Comstock Rick, immediate past president of the Coalition for the Advancement of Medical Research, a group of patient organizations that has been lobbying for more federal funding.

"'We were really looking forward to research finally moving forward with the full backing of the NIH. We were really looking forward to the next chapter when human embryonic stem cells could really be explored for their full potential. This really sets us back,' Rick said. 'Every day we lose is another day lost for patients waiting for cures.'"

CBS News on ruling and “snowflake adoptions”

CIRM Director Prieto Says hESC Research Ruling 'Almost Beyond Belief'

CIRM Director Francisco Prieto, a Sacramento physician, sent in the following comment on our item on today's ruling temporarily halting federal funding of hESC research.

"I think you're opening hits the nail on the head: this decision 'makes clear the importance of alternative funding sources such as the California stem cell agency.' It is almost beyond belief that the court could find that the plaintiffs really met the high standards for a preliminary injunction to call an immediate halt to Federal runding, i.e. that 'there is a substantial likelihood of success on the merits; (2) that the plaintiff would suffer irreparable injury absent an injunction; (3) that an injunction would not substantially injure other interested parties.' I believe none of these are true. Certainly researchers using adult stem cells have had unfettered access to compete for NIH funding since the Bush decision in 2001, and continue to be able to compete for funding. It seems almost obvious that this decision if upheld would injure substantially other interested parties - all the millions of people with chronic disease who hope that this research may lead someday to a cure."

California Stem Cell Agency Deplores Ruling Nixing Fed hESC Research

A federal judge today put a temporary halt to federal funding of research involving human embryonic stem cells in a move that makes clear the importance of alternative funding sources such as the California stem cell agency.

Some had questioned the relevancy of the state's $3 billion research effort after the Obama administration restored cash for hESC grants. Critics said California was no longer needed because the feds were back in the game. But despite the ruling today, the state can proceed with its research because it is not constrained by the federal law cited in the court action.

Today's ruling is not a final decision in the case and is likely to be appealed. But it could mean that NIH funding in this controversial area will be stymied for some time, depending on the legal skills of its attorneys. Meanwhile, California will remain the largest source of hESC funding in the nation, although it has been moving into other areas as well. In fact, some have criticized the agency for not continuing to focus intensely on hESC research, which was the justification for spending $3 billion that was presented to voters in 2004.

In a statement, CIRM said it “deplored” the ruling, declaring that it was “immoral.” CIRM said its research would continue unabated, but noted that today's ruling will have a major negative impact elsewhere.

CIRM President Alan Trounson said,

“The decision is a deplorable brake on all stem cell research. Many discoveries with other cell types, notably the so-called reprogrammed iPS cells, would not happen without ongoing research in human embryonic stem cells. This decision leaves CIRM as the most significant source of funding for human embryonic stem cells in the U.S.”

CIRM Chairman Robert Klein said,

“It would be immoral to unnecessarily delay the critical medical research that is vital for human embryonic stem cell therapies to reach patients suffering from chronic disease and injury. We must remember that the microscopic cells used for this research would otherwise be thrown away by in vitro fertilization clinics, by couples that had finished their family planning.”

CIRM's statement said,

“Under this decision, even research using on the hESC lines approved by President George W. Bush will be halted.

“However, CIRM will continue to fund research on all hESC lines recognized by the Bush administration as well as newer lines approved by the National Institutes of Health during the past eight months. This points to the importance of CIRM’s California model of sustained funding in this field that promises to create thousands of jobs in California as well as improved therapies for patients in Californian and around the world.

“With federal funding uncertain, CIRM will continue providing a stable source of funding for those researchers who have committed their labs to pursuing new therapies based on work with human embryonic stem cells. Through this ongoing funding, CIRM expects to be able to continue to leverage California’s investment through its Collaborative Funding Partners, grant-making agencies in seven countries and Maryland and New York.”

The statement continued,

“CIRM will also continue to fund research with other types of stem cells, particularly progenitor cells that can create many cell types and other pluripotent cells such as induced Pluripotent Stem cells (iPS cells). However, it is important to note that work in all these cells types requires insights gained through work with hESCs to proceed with maximum efficiency. hESC research informs the entire field.”