Major Sickle Cell Surge: Feds and California Collaborate on Cell Therapies for the Disease

In August, the stem cell agency staged a live event on Facebook dealing  with 

the current state of sickle cell research. It has since received  more than 2,200

 page views. Here is a link to the event, which featured  Don Kohn of  UCLA  and 

Mark Walters of UCSF Benioff Children’s Hospital. 

California's stem cell agency has embarked on what it calls a "remarkable" collaboration with the federal government aimed at developing cell-based and gene-based therapies for sickle cell disease, which affects 100,000 persons nationwide.

The partnership marks the first time that the state agency has partnered directly with the National Institutes of Health(NIH), which spend $100 million a year on sickle cell research. 

The NIH has committed an additional $7 million to jump start its new effort, dubbed "The Cure Sickle Cell Initiative."   The California stem cell agency has already pumped nearly $39 million into sickle cell research. 

The affliction is caused by a genetic defect that deprives the body of oxygen, "wreaks havoc on the body, damaging organs, causing severe pain, and potentially leading to premature death," says the NIH. 

In the agreement (see below) with California's $3 billion stem cell agency, the NIH said that the agency is "a recognized leader in the development and funding of clinical trials focused on cell-based therapies and is now working to accelerate support for clinical stage candidate treatments that demonstrate scientific excellence."

Millan told directors in in June that the arrangement amounted to a "quite remarkable" recognition of CIRM's capabilities. She said the NIH "made a decision that they needed to partner with us in order to have the best shot at accomplishing what they want to do with this 'cure sickle cell initiative.'"

On Thursday, directors of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, will receive a more complete briefing about the full range of CIRM's involvement.

CIRM will handle the funding processes for the applications for the late stage research program, making funding decisions in as little as 85 days. The agency's work will include scientific peer review, contracting and post-award management, according to CIRM documents. (The documents are part of the presentation that can be found here.)

Millan said that the NIH has recognized the agency's value in terms of accelerating development therapies, building late development research and translating basic research into clinical use. 

The agency said it will provide funding on approved awards for work done in California, according to CIRM rules. It will have the ability, in consultation with the NIH,  to suspend or terminate research if milestones are missed, including taking back unused funds. Kevin McCormack, a spokesman for the agency, said that it will be compensated by the NIH for additional work that it has to perform but that details are yet to be worked out.. 

Last month, the NIH said in a news release:

"Currently, the only cure for sickle cell disease is a bone marrow transplant, a procedure in which a sick patient receives bone marrow from a healthy, genetically-compatible sibling donor. However, transplants are too risky for many adults, and only about 18 percent of children with sickle cell disease have a healthy, matched sibling donor.

"The Cure Sickle Cell Initiative seeks to develop cures for a far broader group of individuals with the disease, and it is initially focusing on gene therapies that modify the patient’s own hematopoietic stem cells (HSCs), which make red and other blood cells. These modified HSCs can then be given back to the patient via a bone marrow transplant, making a cure available to more patients who lack a matched donor."

Below is a CIRM video on sickle cell disease and a copy of the agreement between the stem cell agency and the NIH. 

(Editor's note: An earlier version of this item incorrectly reported that the agency had committed more than $200 million to sickle cell research, based on inaccurate figures on the CIRM web site. The correct amount is $38,8 million. CIRM said the error was created by a computer glitch and that it has corrected the figures on its site.)

Sickle Cell Cirm-nhlbi Mou ... by on Scribd

Advancing Science, Avoiding Harm: New Fed Rules to Raise Curtain on Clinical Trial Results

The Wall Street Journal today carried a piece about sweeping, new federal research disclosure rules aimed at beefing up the public accessibility of findings of clinical trials backed by billions in public dollars.

The regulations are targeting what Francis Collins, head of the National Institutes of Health (NIH), has called a "disappointing" record of publishing clinical trial results.  He said that "both real and potential harm can result from failure to fully disclose the results of clinical trials."

The regulations are scheduled to roll out somewhat slowly but have been more than 20 years in the works. The Journal reporters, Daniela Hernandez and Amy Dockser Marcus, wrote online today,

"The new rules are part of a push for greater transparency and accountability for the NIH's huge investment in biomedical research. In the past, many organizations have failed to properly register studies and report their findings, actions that NIH officials say result in misspent funds, potential human harm and a lack of public trust in science. The NIH spends roughly $3 billion annually on clinical trials."

Violation of the rules carries the possibility of fines running up to thousands of dollars a day plus endangerment of future funding from the NIH.

Already at one California university, the requirements have increased the workload. The WSJ reported,

"Stanford University School of Medicine is 'adding five or six full-time employees to our overall infrastructure for human research,' said Mark Cullen, senior associate dean for research.

"Dr. Cullen said many of his researchers are still worried and confused about how the new policies will affect their work; the new hires are meant to add to an existing support system made up of roughly 100 staffers."

The NIH is particularly interested in reporting research that has negative results. The WSJ wrote,

"Under the old rules that required publication in journals, negative results often remained undisclosed because journals prefer to publish positive findings.

"'The release of negative results not only prevents duplication and potential unnecessary risk to human volunteers, it also advances our understanding of the science,' said NIH’s Dr. (Carrie) Wolinetz (NIH's associate director for science policy).

In 2015, Collins and Kathy Hudson, then NIH's deputy director for science, outreach and policy and now executive director of the People-Centered Research Foundation, wrote in JAMA,

"If the clinical research community fails to share what is learned, allowing data to remain unpublished or unreported, researchers are reneging on the promise to clinical trial participants, are wasting time and resources, and are jeopardizing public trust.

"The scientific community has a disappointing track record for dissemination of clinical trial results.

A "Blind" Warning to Patients: Beware Unproven, Unregulated Stem Cell Treatments

“Disastrous” is how the New York Times this week described an ostensible stem cell treatment in Florida that left three older women blind or nearly blind. "Chilling reading" said the $3 billion California stem cell agency.

If you haven’t read about the matter yet, it is worth some attention. Denise Grady of the New York Times wrote,

“The cases expose gaps in the ability of government health agencies to protect consumers from unproven treatments offered by entrepreneurs who promote the supposed healing power of stem cells.”

Her article was based on a report in the New England Journal of Medicine that dug into the medicial and scientific details.

The matter involves loosely or non-regulated stem cell treatments in clinics that have shot up around the country, Paul Knoepfler, a stem cell research at UC Davis, and Leigh Turner, a bioethicist at the University of Minnesota, reported last year that at least 570 exist around in the country, with the most in California.

Kevin McCormack, director of communications at California's stem cell agency, wrote about the Florida matter on the agency's blog, He said,

"The report makes for chilling reading."

McCormack said it is a "warning to all patients about the dangers of getting unproven, unapproved stem cell therapies."

Knoepfler wrote on his blog,

“Is this just the tip of the iceberg for negative stem cell clinic outcomes given that there are around 600 such clinics in the US today largely operating generally without FDA approvals, lacking preclinical data to support what they are doing, and experimenting on thousands of patients for profit? 

“Where was the FDA in all of this and are they doing anything about it now?”

Knoepfler continued,

“The clinicaltrials.gov website remains a great, but also very problematic resource. Many patients seem to view anything listed on there as a legitimate, NIH-approved full-blown clinical trial and some clinics encourage that view, but that’s clearly not the case. I interviewed the leader of clinicaltrials.gov in 2014 and problems were already apparent to me back then from that discussion. Clinicaltrials.gov needs to provide patients with much more information (e.g. IND status, fee as inclusion criteria, etc.) and consider excluding certain listings.”While it is quite possible that it lacks the budget, the flexibility, and/or the authority to make such changes quickly, a lot is at stake. They need to make changes ASAP.”

Pigs and People: Growing Human Organs in Animals, Changes at the Federal Level

Last week's news that the federal government is moving to lift its ban on funding research involving human-animal hybrids is a bit of old hat in California.

The state's $3 billion stem agency has long been okay with such research and has well-established protocols to ensure that it is conducted ethically and safely.

Last year, the agency, formally known as California Institute for Regenerative Medicine (CIRM), reported (see below) on its activities to the National Institutes of Health, declaring,

"CIRM has reviewed twelve protocols at seven different institutions where stem cells or neural progenitor cells were introduced into vertebrate animals. CIRM found that all protocols were reviewed and approved by a SCRO(standards review) committee consistent with CIRM requirements."

The Chimera of Arezzo -- photo by Joe deSousa

The announcement that the NIH is once again likely to fund the creation of chimeras -- organisms composed of genetically different cells -- received a significant amount of attention in the media. But none of the stories noted the origin of the word in Greek mythology, where it signified a fire-breathing female monster with a lion's head, a goat's body and a serpent's tail.

Sara Reardon of Nature wrote,

"Chimeras are a growing area of research. Currently, researchers use them to study early embryonic development and to create animal models of human diseases. But one major goal is to engineer animals to grow human organs. The organs could later be harvested from the adult animal and used for transplantation into a patient."

Kevin McCormack, senior director of communications for CIRM, told the California Stem Cell Report, last April,

"On a purely theoretical level CIRM has no objection to growing replacement organs or tissues in pigs, provided it met all CIRM’s rules and regulations. We fund research that does that all the time with mice and rats. Right now none of the research we fund is being used to do that."

Shen Ding -- Gladstone photo

Lenny Bernstein wrote in the Washington Post that researcher Shen Ding at the J. David Gladstone Institutes in San Francisco and who has received $6.7 million in research funding from CIRM, sounded a note of caution.

"While he does not favor the current (NIH) moratorium, Ding said, he believes scientists in this field must move slowly because 'we don't know how to precisely control where and how [cells] might contribute' to different organs."

Bernstein noted,

"The NIH imposed its temporary ban on funding last September, citing ethical concerns. These include worries over animals whose brains might contain human brain cells and what might happen if chimeras were able — and allowed — to reproduce."

The NIH is accepting comments over the next several weeks and then is expected to move forward with its proposal, perhaps with changes.

For Hank Greely, a Stanford law professor, it's about time. Last spring, he wrote an op-ed piece in the Los Angeles Times and said, 

"Today we face the possibility of babies getting organs grown in human/nonhuman chimeras — beasts that are pigs except for a single human organ. To the uninitiated, this may sound more like the dark arts than modern medicine, but pursuing careful research and potential clinical use of these chimeras is both proper and important."

  CIRM Statement to NIH re Chimera Research by DavidJensen on Scribd

California's Bob Klein Proposes $100 Billion, International Stem Cell/Genomics Venture

The man some consider the father of the California stem cell agency has come up with another grand research plan – a $100 billion, 14-nation effort plus California, along with creation of a federal research “trust.”

The proposal comes from Robert Klein, who led the 2004 ballot campaign to create the $3 billion state stem cell agency. He was also its first chairman and a figure revered by some.

Katherine Connor of the San Diego Transcript reported today on Klein’s quest for a “new paradigm in funding scientific research.” During remarks at an oncology symposium yesterday at UC San Diego, Klein said his collaborative venture is needed given the current state of federal research funding. 

Connor wrote,

Robert Klein

“Klein is working on spearheading such a collaboration, where 22 different partners -- including 14 nations, the NIH and the state of California -- commit to long-term funding of scientific research on stem cells and genomics via a World Bank bond. The money invested by each partner would be used to fund work by that entity." 

Connor continued,

“He said if Congress would appropriate a long-term commitment to support this international bond, the research community could leverage it up to a $100 billion program with surplus funds around 35 to 40 percent more than what each individual country or partner could raise from the same amount of money.” 

Klein is a California real estate investment banker who works closely with bond financing. He said his proposed research venture “would go a long way in diffusing the ingrained competitive attitude toward funding.”

Connor continued,

“'The fundamental problem here is that, long term, we have difficulty holding these interest groups together,' Klein said. ‘In California, with Prop. 71, the way it approached that was if you have a unitary decision, you’re either for the bond or against the bond. You can’t go and say 'I want my appropriation,' you have a unitary decision -- it brings all those groups together as a coalition, they have to work together.’”

Scripps' Top Faculty Wants Marletta Removed as President

The turmoil at the highly regarded Scripps Research Institute today intensified as its top faculty called for the removal of its president, Michael Marletta, who is involved in an effort to merge the organization with the University of Southern California (USC).

The demand was reported today in the San Diego U-T by Bradley Fikes and Gary Robbins. They wrote that the faculty leaders “have lost confidence” in Marletta, who assumed his position in January 2102.  

 Scripps is running a $21 million deficit for the fiscal year ending Sept. 30. Grants for biomedical research are tight and donations to Scripps are not meeting the institute’s long-term needs. Scripps derives more than 86 percent of its funding from the NIH, which is under stringent federal budget constraints.  The negotiations with USC are now in a “deep freeze,”  Fikes and Robbins reported yesterday.

 The faculty made the call for his removal in an email last night to Scripps Board Chairman Richard Gephardt, the former majority leader of the House of Representatives and now a Washington lobbyist.  He told Fikes and Robbins in an email today that the board understands a “variety of perspectives” exist concerning the future of Scripps. The San Diego newspaper did not immediately carry a response from Marletta.

Peter Farrell, another Scripps board member and executive chairman of ResMed, did not welcome the call for Marletta’s removal. He told the San Diego U-T,

 “If you’re on the board, you say, ‘Who’s running this ship, guys? You can make suggestions, but you cannot demand action. In other words, the board’s being told what it’s got to do, and if you don’t do this, we’re going to take our bat and ball and go home.”

Fikes and Robbins wrote,

“Farrell expressed sympathy for the faculty, but said Marletta is working with the best interests of Scripps Research at heart.”

In an online comment on the U-T Web site, Jeanne Loring, director of the Scripps Center for Regenerative Medicine,  said,

"Why would a board member of an organization 'feel sorry' for a group that brings in 86 percent of the funding for that organization? That makes no sense. Is he suggesting that we take our money elsewhere?"

Regarding Loring's comment concerning funding, for those unfamiliar with the way many nonprofit research organizations operate, it is on the same principle as a beauty parlor. In a beauty parlor, a beautician rents a chair and shares his/her income with the owner of the business. If the beautician’s income drops off, he or she is out the door. Likewise, scientists receive space and support at facilities like Scripps. Their obligation is to keep the grant money rolling in the door. The research organization then takes a healthy cut.

Fikes and Robbins wrote that Scripps has been a pillar of “biomedical brain power.”  But they said the scientific achievement has not been matched by fundraising since Marletta was named as president.  They wrote,

“During that time, Salk and Sanford-Burnham (both located near Scripps) have raised great sums of money. In January alone, Sanford-Burnham received an anonymous $275 million donation in January, to be given over 10 years.

“During the last couple of years, the Salk Institute has raised $275 million in a capital campaign, although Salk has far fewer faculty than does Scripps Research.”

Scripps has declined to disclose its fundraising figures, the U-T reported.

So far the Scripps-USC negotiations and turmoil have attracted little attention in the scientific media. However, that is likely to change this month in the wake of the increasing turbulence. 

Post-Mortem on NIH and its Stem Cell Center Action

An interesting discussion is underway in comments on this blog concerning the shuttering of the NIH Center for Regenerative Medicine and the departure of its leader, Mahendra Roa.

It involves priorities, strategy and funding, which one anonymous commentator says was inadequate. Researcher Jeanne Loring of Scripps has also weighed in with her thoughts. Among other things, she said that Rao did tremendous work and that the California stem cell agency should "embrace his ideas." Another scientist says some of the problems stemmed from failure to negotiate the bureaucratic byways of the NIH with the necessary skill. All the remarks can be found in a comment string on the NIH item. 

NIH Action on Stem Cells: More Than 'Bureaucratic Bungling'

A national stem cell advocacy group this week ripped the National Institutes of Health (NIH) for “dismantling” its Center for Regenerative Medicine, describing the move as a "setback" for the entire field.

Bernard Siegel
GPI photo

The Genetics Policy Institute (GPI) said the action was a “huge disappointment” in an email sent out internationally by Bernard Siegel, executive director of the group, which stages the heavily attended World Stem Cell Summit.

The NIH move also has implications for the California Institute for Regenerative Medicine(CIRM), whose $3 billion program is down to its last $600 million.

The GPI was reacting to news in the journal Nature that the NIH said its center “will not continue in its present form.” The head of the NIH program, Mahendra Rao, took a job this month with the New York Stem Cell Foundation. James Anderson, director of the NIH’s Division of Program Coordination, Planning, and Strategic Initiatives, told Nature that the $52 million NIH effort was going to be rethought following a workshop in May.

Siegel said,

“The dismantling of the program appears to be a retreat by the United States from the translational imperative and a setback for the field at large. The patient community will be looking to Dr. Collins(head of the NIH) and others in NIH leadership to fulfill their commitment to stem cell development as a singular priority. Other countries are pouring in resources and moving full steam ahead. The NIH’s failure to continue the program represents more than just a case bureaucratic bungling. What we see here is a lack of vision and a public relations blunder. Years of valuable work and planning just tossed away. The scientific community and the public rightfully believes regenerative medicine will one day provide innovative treatments and cures to chronic diseases. The decision to tear down the Center for Regenerative Medicine, without first providing an alternative plan, undermines the credibility of NIH. A huge disappointment."

Asked for a response this week by the California Stem Cell Report, Amanda Fine, a public affairs specialist at the NIH, said in an email,

“The NIH Intramural Center for Regenerative Medicine has not closed.  This is a fast evolving area of science and NIH decided to step back and reassess what the field needs in 2014 and beyond and where NIH can have the greatest impact. NIH is holding a workshop tentatively scheduled for May 5 that will convene a group of experts in the field to address current obstacles to translation of cell therapies and will help prioritize a number of requirements that the larger community has articulated through white papers over the past two years.  NIH will consider the feedback from the workshop and establish a set of goals for the CRM.

Initially, Fine asked that the NIH statement not be attributed to a specific individual but later

said it could be attributed to James Anderson, who also made the statements to Nature.

Public details of the NIH program and its problems are murky. But the NIH action has implications for the California stem cell agency, which is scheduled to run out of cash for new awards in 2017. The agency is attempting to raise funds to continue beyond that point.

The agency could use the news to argue that now, more than ever, it is necessary to support stem cell research efforts in California because of weak federal support, which ebbs and flows depending on political vagaries. On the other hand, some might interpret the NIH rollback as a sign that those well-informed in the field have judged it to be less-than-ready for prime time, an argument that could be extended to California's efforts.

What the NIH action clearly does is create more uncertainty concerning progress in stem cell research. Uncertainty is an anathema to businesses that may be considering where to invest hundreds of millions of dollars.

New Collaborative Agreement Announced Between California Stem Cell Agency and NIH

The California stem cell agency and the NIH today announced a collaborative agreement aimed at accelerating the transformation of basic research into cures.

The agreement came up several times during this morning's discussion of changes in CIRM's strategic plan in the context of leveraging the agency's efforts. Some directors indicated that the agreement could mean that CIRM could spend less on costly translational grant rounds. Here are some excerpts from the agency's press release.

"The memorandum of understanding signed by CIRM President Alan Trounson and Michael Gottesman, Deputy Director for Intramural Research at NIH, is a pilot project of these partnerships in clinical and translational research. This MOU establishes a framework to advance the complementary and synergistic goals of CIRM and the NIH to 'help NIH and CIRM researchers work together to bring their special talents in stem cell and regenerative medicine research to bear upon prevention, diagnosis, and treatment of various diseases.'"

"The NIH, through its trans-NIH Center for Regenerative Medicine (NIH CRM), the NIH Clinical Center, and the newly established NIH Center for Translational Therapeutics (NCTT), will foster these interactions. The NIH Clinical Center is the world’s largest hospital dedicated entirely to clinical research. The Center houses basic, translational and clinical research efforts of the NIH intramural research community, including the recently established NIH CRM funded through the NIH Common Fund."

The press release also mentioned possible opportunities for collaboration. It said,

"One relates to the current round of applications for CIRM’s Disease Team Therapy Development Research awards. During the planning phase of these awards, California teams could develop collaborations with researchers at the NIH Clinical Center on various aspects of a preclinical, Phase I, Phase I/II or Phase II clinical trial. Another option is to enable California researchers with the opportunity to take part in NIH Clinical Center visiting fellowship or clinical investigator training programs. A third is to access unique resources they could apply to use that may not be available at their home institution."

Rao Leaving the Golden State for NIH

California stem cell researcher Mahendra Rao is returning to the NIH after five years as vice president at Life Technologies in Carlsbad, Ca.

NIH Director Francis Collins yesterday announced that Rao will be director of the NIH Intramural Center for Regenerative Medicine. The new center is an effort by the NIH to speed development of stem cell therapies.

Rao left the NIH in 2006 because he was restricted in his work on human embryonic stem cells. He said he could not do the job he was hired to do so he left.

While in California, Rao was connected to the Buck Institute for Age Research in Northern California and was involved in the activities of the California stem cell agency.

The NIH did not announce Rao's salary.

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”

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.”

NIH and Exculpation

For those of you not fully informed of the tricky byways of stem cell science, the Boston Globe carried a nuanced editorial today that laid out the significance of an arcane “exculpatory” matter last week

Arcane, that is, to folks who do not fiddle with human embryonic stem cells.

The case involved possible use in federally funded research of embryos donated some years back. The feds said no because they were given under conditions that do not meet today's ethical tests, although the donations met the standards of the day, which actually was only a decade or two ago. The Globe called the NIH action a “major blow.”

You can read all about it here.

New NIH Conflict Rules and Their Impact on CIRM

The NIH today unveiled proposed new conflict-of-interest rules that will reach deep into stem cell research circles in California, touching the state's stem cell agency and affecting 40,000 scientists nationwide.

Francis Collins, director of the NIH, said the rules are aimed at preserving public trust in research ethics and the “integrity of the scientific enterprise.”

According to a report on GenomeWeb News, Collins said,

"As the NIH director, I think I can say with great sincerity that the public trust in what we do is just essential, and we cannot afford to take any chances with the integrity of the research process."

Rob Stein of the Washington Post wrote,

“Among other changes, the new guidelines will reduce from $10,000 to $5,000 the minimum payment that researchers will be required to report and mandate that universities, colleges, research institutes, businesses and other entities that employ researchers who receive NIH funding monitor compliance with the new reporting requirement. Funding information would have to be posted on a publicly accessible Web site. Violators could be subject to losing their funding.”

The rules would require recipient institutions to create a Web site that would display the statements of economic interests filed by their faculty. Some institutions, such as Stanford, already do that. Stanford labels the pages as “industry relationships.”

The NIH announcement focuses new attention on a recommendation last January that CIRM post on the Internet the statements of economic interest filed by members of its board of directors. A sister organization to CIRM, the Citizens Financial Accountability Oversight Committee, said that CIRM should follow the example of California Gov. Arnold Schwarzenegger. He requires his appointees to file their economic interests online along with their monthly expense claims. State Controller John Chiang, the state's top fiscal officer and chairman of the oversight committee, said the postings and other changes were needed to improve transparency and accountability at CIRM.

Last Friday, the California Stem Cell Report asked Don Gibbons, CIRM's chief communications officer,  whether the agency intended to act on the recommendation for online postings. We have received no response.

The NIH requirement is also likely to raise questions about CIRM's policy of secrecy concerning the economic interests of the scientists who make the de facto decisions on CIRM grants. Currently grant reviewers only have to disclose their interests to a select group within CIRM. Applicants (and the public) have no way of knowing the economic or professional interests of scientists who review their applications. However, with the new NIH rule, virtually all of those scientific reviewers, given the likelihood they hold an NIH grant, will have to post their economic interests at their home institutions but not at CIRM.

Some influential groups have taken positions indicating the proposed NIH rules are not strict enough. Jocelyn Kaiser of Science magazine wrote,

“Although these are big changes, they fall short of advice from an Institute of Medicine panel and the Association of American Medical Colleges (AAMC). Both think that researchers should report all potential financial conflicts to their institutions, with no minimum dollar threshold.”

Some Question CIRM Grant Oversight as Excessive

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

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

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

The Scientist article by Jef Akst said,

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

She continued,

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

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

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

She said,

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

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

Akst's story said,

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

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

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

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

More on the Tale of Three Terminations

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

CSCR Withholds Names of Terminated Grantees to Avoid Unnecessary Harm

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

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

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

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

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

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

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

Consumer Watchdog Seeks Alteration of NIH Plan

Citing the “perverse effect” of proposed NIH stem cell research rules, the Consumer Watchdog group today called for changes in the guidelines along the lines recommended by the California stem cell agency and the Interstate Alliance on Stem Cell Research.

John M. Simpson, stem cell project director of the Santa Monica, Ca., group, said that the NIH plan would bar funding of research that had received financial support from the Bush Administration.

In a press release from his organization, Simpson said,

"Most of us were heartened when President Obama lifted Bush Administration restrictions on funding stem cell research, but the perverse effect of these proposed NIH rules is that the limited research scientists were able to conduct under Bush will now be ineligible for federal funding,

"Certainly this is not what President Obama intended and the regulations must be modified."

Simpson also noted that comments can be sent to the NIH online at the following Web site: http://nihoerextra.nih.gov/stem_cells/add.htm