'California Has Changed Everything'

Christine Vestal at Stateline.org has prepared an excellent and timely overview of funding for human embryonic stem cell research, which was obviously in the works prior to the president's speech earlier this week.

California receives a fair amount of attention, but she provides a good update on efforts in other states and at the national level as well.

Here is an excerpt dealing with the Golden State:

"'California changed everything,' said Bernard Siegel, founder of the Genetics Policy Institute, a non-profit stem cell advocacy group. 'No state wanted to see their best scientists pick up and move to California,' he said. As Gov. Arnold Schwarzenegger (R) predicted when California voters approved their landmark 2004 ballot measure authorizing the stem-cell investment, the message has gone out to 'the world’s scientific elite and aspiring students that, in California, you will find the resources and the freedom to expand the frontiers of science.'

"Now that grant money is flowing, the California Institute of Regenerative Medicine (CIRM) reports it has wooed more than two dozen of the world’s top stem-cell scientists, including Japanese scientist Shinya Yamanaka, who lead the most recent skin-cell discoveries at the University of Kyoto. Yamanaka accepted a state grant in August 2007 and began working part-time in San Francisco to avoid stem-cell restrictions in Japan."

Snippets: Stem Cell Lending to Pizzo Profile

Biotech Loan Program – Coming up Feb. 19 is another CIRM hearing on its ambitious plans for a biotech loan program. This session will be in La Jolla with a teleconference link to San Francisco. If you want to take part in developing the criteria for the effort, which is the brainchild of California stem cell chairman Robert Klein, you should plan on attending or at least sending comments to CIRM. The program could total as much as $750 million, according to Klein, and is aimed at financing development of stem cell therapies in cases where conventional financing is not available. The schedule also calls for a presentation on the plan to the Oversight Committee at its March meeting.

Bush v. CIRM -- The California stem cell agency's statement concerning President Bush and his comments this week regarding stem cell research stirred a mini-debate on a bioethics blog run by Los Angeles physician Maurice Bernstein. You can find the exchange here.

Pizzo Profile – The Fordham alumni magazine carried a nice profile of Philip Pizzo written by Carl Hall, who has covered stem cell issues for the San Francisco Chronicle. Pizzo (see photo from Stanford) serves on the CIRM Oversight Committee and is dean of the Stanford School of Medicine. Among other things, the piece says:

"Even some of the most persistent critics of the California stem cell enterprise credit the value of Pizzo’s steady ethical compass during debate over public oversight and financial standards. While other members of the stem cell governing board filed lengthy financial disclosures, including a fair share of monetary ties to biomedical concerns, Pizzo’s declaration was essentially a blank slate: He steers well clear of any entangling investments, a pattern that can be traced back to his days at the National Institutes of Health (NIH), where he was head of the infectious disease section of the National Cancer Institute from 1980 to 1996."

The piece appeared in the summer issue but we ran across it only recently.

A View from the East

For another perspective on the California Stem Cell Report and whether it follows the party line of the California stem cell agency, curious readers can take a look at the Ipbiz blog produced by Larry Ebert in New Jersey.

On Tuesday, Ebert described this report as a "fantasyland." Today he suggested the report was something of a tool of California's stem cell agency.

California patient advocate Don Reed also weighed in. His comments are contained at the end of the Tuesday item.

Investors to Bush: We Like hESC

While the current president is reiterating his opposition to human embryonic stem cell research, investors are beginning to look to the future.

We have reported previously that the prospect of a favorable presidential change has eased some of the fears of stem cell investors. One further sign is the announcement today that UBS Investment Research upgraded Geron Corp. of Menlo Park, Ca., from neutral to a buy recommendation on its stock.

Thomson Financial reported the move and said,

"'We think Geron could be an attractive U.S. presidential election year play, given that any change in the current administration is likely to create a more favorable environment overall for stem cell research efforts and funding,' said analyst Graig Suvannavejh.

"Suvannavejh also pointed to positive near-term catalysts such the filing of an investigational new drug application for Geron's stem cell therapy for spinal cord injury and an update on the company's partnership with Merck for telomerase-based vaccines."

Geron hit a 52-week high of $9.85 last May and a low of $4.40 last week. At the time of this writing, it was trading at $5.16.

Hawgood Joins CIRM Directors

The California stem cell agency has its second Aussie on board, Sam Hawgood, who joined CIRM's Oversight Committee at its meeting in Burlingame earlier this month.

Hawgood (see photo) replaces David Kessler, the former dean of medicine at UC San Francisco, on the Oversight Committee. Kessler was fired as dean in December and could no longer serve on the Oversight Committee. California law states that the Hawgood/Kessler position must be filled by an executive officer from a UC campus with a medical school. The appointment is made by the chancellor at UC San Francisco.

Hawgood emigrated from Australia in 1982. Another Australian, Alan Trounson, was named last year as president of CIRM. Here is part of what UCSF had to say about Hawgood at the time Kessler was fired.

"Hawgood was named chair of pediatrics in 2004 and physician in chief of UCSF Children’s Hospital, one of the nation’s top children’s hospitals. He also has been instrumental in laying plans for construction of a new children’s hospital at UCSF Mission Bay. He is currently president of the UCSF Medical Group, which represents more than 900 physicians at UCSF."

Neither CIRM nor UCSF issued a news release on Hawgood's appointment nor does the CIRM website yet contain any biographical material on Hawgood.

CIRM To Bush: Harmful and Wrong

The California stem cell agency is accusing President Bush of distorting facts and performing a disservice to millions of Americans who suffer from chronic diseases and injuries.

The agency said Bush intends to "further limit" research into human embryonic stem cells.

The CIRM statement is contained in a press release on its web site that concerned Bush's speech Tuesday night. Interestingly, the CIRM statement is not attributed to either Bob Klein, chairman of the agency, or its new president, Australian stem cell researcher Alan Trounson. In the past, statements such as this have been linked to either the president or chairman.

Here are excerpts from the release followed by the two paragraphs from the president's speech.

"President Bush distorted the scientific facts on stem cell research and did a disservice to the millions of patients suffering from chronic disease and injury for whom stem cell research holds great promise for future therapies and cures."

"The President’s proposals to further limit medical research in this area fail to take into account the intricate realities of the state of stem cell research. Indeed, the recent advances in which skin cells were induced to become pluripotent would not have been possible without research involving human embryonic stem cells."

"Therefore it is critical that all avenues of stem cell research be aggressively advanced. To do otherwise would increase the already devastating restrictions that have burdened Federal support of stem cell research and patients who are depending upon it. This Administration’s position on stem cell research has already cost years in lost research productivity. Further restrictions would result in more lost time in developing stem cell based therapies and cures that hold great promise to alleviate suffering for the most destructive and costly diseases such as spinal injury, loss of sight, heart muscle injury, Parkinson’s Disease, ALS and diabetes."

Bush's comments:

"On matters of life and science, we must trust in the innovative spirit of medical researchers and empower them to discover new treatments while respecting moral boundaries. In November, we witnessed a landmark achievement when scientists discovered a way to reprogram adult skin cells to act like embryonic stem cells. This breakthrough has the potential to move us beyond the divisive debates of the past by extending the frontiers of medicine without the destruction of human life.

"So we're expanding funding for this type of ethical medical research. And as we explore promising avenues of research, we must also ensure that all life is treated with the dignity it deserves. And so I call on Congress to pass legislation that bans unethical practices such as the buying, selling, patenting, or cloning of human life."

Coming Up

After a brief hiatus traveling through Arizona and New Mexico, we are back in Romantic Old Mexico where we are performing romantic boat chores (fiberglass work, installing 400 pounds of batteries and repairing a diesel engine). All of which is preparation for dropping the boat back in the water(currently she is on jackstands in a boatyard, which has four huge, red silos of fish oil as its centerpiece). Later today we will be posting some fresh items on this site. We hope all of you can withstand the suspense.

Coverage of the Cloning of the Cells of Sam Wood

While CIRM was advancing its $262 million lab grant program this week in Burlingame, about 490 miles to the south in La Jolla, a tiny firm called Stemagen was making international headlines with its news about cloning human embryos.

Terri Somers of the San Diego Union-Tribune had one of the first stories on the matter. The paper also had a piece by Sandi Dolbee on the ethics of the issue. The blog of the American Journal of Bioethics has a roundup of links to coverage elsewhere.

The Center for Genetics and Society in Oakland also raised questions about the propriety of the research, which involved the cells (see Stemagen photo on right) of Stemagen's president, Samuel Wood (see Stemagen photo on left) and an anonymous investor in the firm.

Whatever your take on this, along with all the other news on stem cell research in the last few months, it will generate substantially more attention on the field from investors, scientists, supporters and foes.

Meager News Coverage of Stem Cell Lab Grants

News coverage of this week's $262 million stem cell lab jackpot was very light with only three articles appearing in what is generally considered to be the mainstream media.

One of the pieces was written by yours truly for Wired News (although it may not be considered "mainstream"). Terri Somers of the San Diego Union-Tribune focused on the $50 million bid by the San Diego stem cell consortium, which consists of UC San Diego and the Scripps, Salk and Burnham institutes. The San Jose Business Journal carried a brief item that was a rewrite of the CIRM news release.

No reporters from the mainstream media appeared to be present for the Burlingame meeting of the CIRM Oversight Committee at which the lab grant applications were considered, a coverage trend that is likely to continue this year.

That's a mixed blessing for CIRM. Excessive media attention can lead to stories about the agency's warts. On the other hand, not enough makes it difficult for CIRM to deliver its message and build support for stem cell research.

Declining and meager coverage reflects several realities. The novelty of Prop. 71 has virtually vanished in the eyes of most editors and reporters, who generally don't cover most state agencies with any regularity. Newspapers are also laying off staff. Their budgets are hard-pressed because of declining advertising revenue and the need this year to finance coverage, at least at larger papers, of the presidential campaign and the Olympics in China.

Barring a major scandal, we are likely to see minimal coverage of CIRM this year with a minor blip for the awarding of the lab grants, which will come this spring. That event was scheduled for April 23-24 but CIRM is now considering moving it to May because of the crunch of meetings scheduled for April.

Childrens Hospital Loses Bid for Lab Grant; 12 Survive

In their most heated public session in their short history, directors of the California stem cell agency Wednesday night rejected a bid by Childrens Hospital Oakland Research Institute to overturn a negative recommendation on a grant to build a lab to fight sickle cell anemia.

Childrens' request failed on a 5-10 vote despite an impassioned plea by CIRM director Jeff Sheehy.

"This is a no-brainer," said Sheehy. "This is a very promising area of research."

Other board members argued that Childrens' public appeal, the first ever directed to the Oversight Committee, violated the agency's processes, was unfair to other rejected applicants and needed consideration in some future round of grants.

Sheehy didn't buy the arguments. "Let us study it," he said caustically. "Let another person die."

The board's action came during a session that resulted in the relatively routine approval of 12 institutions to advance to the next round of the $262 million stem cell lab grant program, which will judge the actual building plans. Today's review focused on the research proposed for the facilities. All 12 approved Wednesday night were identified earlier as being recommended for funding following a closed-door session involving scientific reviewers who are not required to disclose publicly their financial interests.

Childrens Hospital received a "do-not-fund" decision by the reviewers. Bertram Lubin, president of the hospital, appeared before the Oversight Committee Wednesday night after sending three letters to the members of the panel. (Two of have appeared on this web site.)

He told directors that the grant reviewers did not appreciate the type of research proposed by Childrens. Sheehy, who participates in the closed-door review sessions, concurred.

Lubin also told directors, "When you report on what CIRM has done, this (funding his program)would be a major accomplishment." He said it could result in actual treatments in a year or two, which is a far cry from almost all of the research financed by CIRM.

Some directors, including Chairman Robert Klein, have pushed aggressively for faster work on therapies. Ironically, earlier in the day, a CIRM Task Force explored details of how it could launch a massive loan program, totaling as much as $750 million, to speed development of therapies.

Gerald Levey, dean of the UCLA School of Medicine, did not agree with Childrens' appeal. "I don't think we can run a board this way. If we do, it would be chaos." He was responding to a request by Lubin for a 10 minute presentation Thursday of Childrens' case. Levey warned that allowing the presentation would lead to 50 other rejected applicants coming to the board.

Director Joan Samuelson said that even 100 persons would be okay with her. She provoked laughter when she declared that would show more interest than at any other board meeting.

CIRM's new president, Alan Trounson, who was attending his first board meeting, expressed concern about whether allowing Lubin to make a 10 minute presentation on Thursday would be fair to the five other rejected applicants. He suggested that they might need to be notified and allowed to make a similar pitch, perhaps by phone.

Ted Love, another director, said, "We can't fund everything. He said that if Childrens' research is "really good," they will find funding elsewhere. Both Klein and Trounson indicated that Childrens research might find favor in another round of grants.

However, the board rejected, on a 3-10 vote with one abstention, Samuelson's motion to permit a 10 minute presentation. Lubin was allowed to make his appeal during the comment period alloted to the general public. Speakers are supposed to be limited to three minute presentations, but enforcement of is sometimes lax.

While Childrens was frustrated in its bid on Wednesday, other applicants are going to be disappointed this spring in the second round of the competition. CIRM staff said that if all 12 were funded at the midrange of the amounts alloted in each category of competition, $320 million would be required. The board has already said it will only spend $262 million.

Following the meeting, CIRM released the following statements:

Klein said,

"Investment in facilities to extend California’s state-of-the art research capacity is a critical part of CIRM’s Scientific Strategic Plan to sustain and build California’s global leadership in stem cell research. Through the Major Facilities Grants we are leveraging the impact of Proposition 71 funds with contributions from donors and non-profit research institutions. Our goal is to exceed $550,000,000 in research facility investments that will advance critical stem cell research. Achieving this goal would mean that every one dollar of State funding from Proposition 71 would deliver two dollars in research facility investment."

Trounson said,

"The facility investments CIRM will make through these grants will continue to propel California as a leader in stem cell research. Providing the necessary infrastructure for research is a critical step in laying the foundation for eventual therapies and cures."

The Oversight Committee meeting will continue today with an appeal by the Human BioMolecular Research Institute San Diego of reviewer rejection of its grant application.

The 12 institutions that survived Wednesday night's judgments are Buck Institute, the San Diego Consortium for Regenerative Medicine, Stanford, UC campuses in Berkeley, Davis, Irvine, San Francisco, Merced, Santa Barbara, Los Angeles and Santa Cruz and the University of Southern California.

The agency's press release is not likely to be available on its web site until sometime Thursday morning.

Fresh Comment

"Anonymous" has posted a new comment on the "seeking summaries" item on Tuesday. We would encourage the commentator to share some of his perspectives on the content of the summaries with readers of this blog. They can be filed anonymously via the comment function.

CHORI Lab Grant Bid Gets Help

The bid by Childrens Hospital Oakland Research Institute today received added support in its effort to reverse a negative decision on its application for a CIRM grant to build a stem cell facility that could help sickle cell anemia research.

The support came in the form of a letter from the Greenlining Institute of Berkeley, which has lobbied CIRM on minority issues in the past.

Here is the text of the missive to the Oversight Committee:

January 15, 2008

Dear Members of the ICOC,

The Greenlining Institute is a multi-ethnic public policy and advocacy organization that is dedicated to improving health outcomes for low-income communities of color in California. Our coalition includes civil rights, health, business, and faith-based organizations such as the First AME Church, the California Black Chamber of Commerce, the California Hispanic Chamber of Commerce, the Asian Business Association, the Mexican American Political Association, the Southeast Asian Center, and the La Maestra Community Health Center.

We are disappointed that the application submitted by Children’s Hospital Oakland Research Institute (CHORI) to CIRM for a Facilities Grant was not approved by the CIRM Working Group Committee. As advocates for minority health and the elimination of health disparities, we do not believe that the working group appreciated that a proportion of CIRM funds provided by the vote of citizens of this State should be used to support programs that address the needs of underserved communities. We believe that the work CHORI proposes is likely to benefit a disproportionate number of citizens as a result of the ethnic diversity in this State. We understand that you have the authority to make the final decision on CHORI’s application and encourage you to approve it.

CHORI’s application included a plan to construct a new GMP cellular facility which would perform clinical and translational research using adult stem cells obtained from cord blood and from placenta. CHORI is recognized as a national resource for cord blood and placental cell studies, and in addition to basic research studies, it serves as a core resource for other investigators. CHORI staff have reported that 92% of children with sickle cell anemia have been cured following an HLA matched sibling cord blood stem cell transplantation. This information has previously been presented to ICOC and was enthusiastically supported. As less than 25% of patients with sickle cell anemia have a suitable donor for a stem cell transplant, the research proposed at CHORI has the potential to expand current transplantation practice in our State and throughout the nation. Not only will this impact health and quality of life, it will have an enormous beneficial economic effect. It appears that the working group did not appreciate the need for CHORI’s GMP facility to successfully carry out clinical trials that would benefit our State.

In light of the state’s swelling budget deficit, we cannot afford to ignore any portion of the state’s population—especially its most underserved. To better ensure that California’s diverse communities be included in the implementation of Proposition 71, we urge you to consider applicants for stem cell research grants who have demonstrated a historical commitment to serve the state’s diverse public. The Children’s Hospital of Oakland Research Institute is one such institution. Thus, we urge you to approve the application submitted by the Children’s Hospital Oakland Research Institute at your meeting on
January 16 and 17, 2008.

Respectfully,
Héctor Javier Preciado
Health Policy Director

Joe Araya Tayag
Program Manager, Health

Business Wants CIRM Millions

Fifteen businesses – perhaps some from outside of California – intend to seek grants from the California stem cell agency, a response that one agency watchdog says demonstrates that the private sector is "comfortable" with sharing stem cell wealth with the state.

The agency today announced that 57 organizations filed letters of intent last Thursday stating that they expect to apply for the $25 million effort to develop new lines of pluripotent cells, including research into reprograming adult cells.

John M. Simpson, stem cell project director of the Foundation for Taxpayer and Consumers Rights, said,

"This demonstrates clearly that responsible California companies are comfortable with the the public interest provisions in the stem cell agency’s intellectual property rules. There were those who claimed to speak for the industry, such as the California Healthcare Institute, who warned the regulations would dampen corporate interest. Clearly that’s not the case. This is an endorsement of the sometimes arduous public process that developed the IP rules. I only wish the agency would be as open and transparent in other aspects of its operation. That’s how you build public trust and support.”

Alan Trounson, the new president of CIRM, said,

"We are particularly excited to note that based on the letters of intent we have received there is a good balance between research that derives pluripotent stem cell lines from human embryonic stem cell lines as well as new, highly novel methods such as iPS."

Firms located out-of-state are eligible to compete for the funds if they have a "research site" located in California by the Feb. 5, the application deadline. CIRM did not specify whether any of the letters of intent came under that category.

Details Emerging on Possible Shape of Big Biotech Loan Program

The California stem cell agency today served up a tasty, albeit late morsel to chew on prior to Wednesday's session on the proposed biotech loan program, which could total as much as $750 million.

The document outlined CIRM's basic thinking at this stage, which includes a staff review of loan applications to see whether they merit further review by scientists.

The document seeks input concerning which of the intellectual policy rules for nonprofits should be used in the loan program. It also asks for comment on the following:

Debt Structure/Terms: E.g., five to seven years?

Interest Rates: Adjusted per risk analysis and/or balancing feasibility and program goals?

Subordination: Should CIRM loan be subordinate to bank, working capital lines, venture loans, et cetera?

Security: What would be appropriate?

Milestones: Appropriate benchmarks for payments over five to seven year term?

The hearing begins at 11 a.m. in Burlingame, Ca.

Rejected Grant Applicant Steps Up its Bid for Approval

The Childrens Hospital Oakland Research Institute has beefed up its effort to overturn the initial rejection of its bid for a multimillion dollar stem cell lab construction grant with a second letter that amounts to a "peer review" of the "peer review" of its plan.

The effort by the institute is believed to be the first such appeal by a rejected applicant, although CIRM refuses to confirm that. It also refused to release the letter, saying such an action would be inappropriate. Earlier today, we filed a formal request for the letter under California's public records law. Later, the letter came to us from a source that asked not to be identified (it was not the Oakland institute).

Both letters were sent Monday to all members of the CIRM Oversight Committee, which meets Wednesday to consider the scientific segment of the lab grant proposals.

Grants not approved on Wednesday and Thursday will be knocked out of the running for the second stage of the grant review, which will focus on the building plan. The current stage focuses on the science that is being proposed.

Last fall the CIRM Grants Working Group conducted a "peer review" of all 17 applications. The review was performed behind closed doors with scientists who did not disclose publicly their financial interests -- standard policy for CIRM. Twelve applicants were recommended for funding. Five were rejected, including Childrens Hospital, the University of California at Riverside and Cedars Sinai.

CIRM has identified the 12, in "violation" of its own policy of confidentiality on the names of applicants. UC Riverside and Cedars Sinai confirmed to the California Stem Cell Report that they were rejected. But they have not responded to questions about whether they are appealing the decisions.

The text of the Childrens letter is below.

Childrens Hospital's Second Letter

Here is the text of the latest appeal letter from Childrens Hospital Oakland Research Institute. The boldface indicates the criticism of the Oakland proposal. CIRM refuses to release the actual report by CIRM reviewers, who performed their review behind closed doors.

January 14, 2008

Dear Members of the ICOC:

The critique of the Grants Working Group indicates clearly that the intent and aims of our proposal were misunderstood. We think that the reviewers might have overlooked that the goal of Proposition 71 was to cure disease by the innovative use of stem cells, not simply to explore the possibility of curing disease with ES-derived cells. The reviewers imply that we have requested a facility that will be used simply to process and store blood stem cells for conventional transplant procedures. This is not the case: we have proposed to explore the use of a new type of blood stem cell, discovered here, that has the potential to transform blood stem cell transplantation and make it available to far larger numbers of patients.

Achievement of this goal will however require rigorous research. The research must be very strongly clinically oriented if our discovery is to be translated into something that can be used to cure disease. We should also note that the cost of our facility is relatively modest, particularly in light of the probable direct and near-term benefit to the citizens of California.

We would like to respond to the principal criticisms of the application:

1. No collaboration with established stem cell lab/groups to help characterize novel cellular populations; absence of hESC studies. The focus of our research and the purpose of the application is to benefit California citizens affected by hemoglobin disorders, which afflict a disproportionate number of citizens as a result of the ethnic diversity in this State, through innovative applications of stem cell therapy. We are committed to accomplishing these aims in the near-term, and more important, to apply our research in the clinic by using the safest and most reliable methods. Currently, there is a great deal of uncertainty surrounding the clinical applicability of hESC, and their clinical safety has not been sufficiently well characterized to support clinical trials with these cells in the near-term. Thus, we have elected to apply other methods of regenerative cellular therapy, in part because the safety, efficacy, and availability of other sources of cells are better developed, and we have considerable experience with conducting these trials.

2. Institutional collaborations were not carefully described, and corporate partnerships to develop the products were not included in the application. While we have established institutional collaborations with UCSF, UC Berkeley, and UC Davis, and share CIRM funding with UC Berkeley to conduct stem cell biology training for our clinical fellows, none of these institutions has developed expertise in characterizing placental stem cell populations, which are the focus of this application. Thus, we are uncertain about how collaboration on this subject outside our group would be practical or useful. It should be evident that we have extensive established collaborations relating to hematopoietic stem cell transplantation and cord blood collection, processing, and storage.

3. Poor interdisciplinary collaboration of pre-clinical and clinical research projects, with a lack of track record by some PIs. This criticism ignores information that was clearly presented in the proposal: in fact we have an extremely well integrated program of research. Our proposals were prepared as a result of ongoing interactions by laboratory-and clinical-based investigative teams to 1) collect stem cell populations from placenta to investigate a new source of stem cells that might augment and expand the applicability of cord blood transplantation; 2) overcome barriers to histocompatibility by using photochemical treatment of donor lymphocytes before hematopoietic cell transplantation with mismatched donors. These projects were initiated, and are undergoing further development, as collaborations between basic and clinical investigators devoted to discovering medical therapies for hemoglobin disorders. The goal of these interactions is to translate these ideas into readily available applications of cellular therapy, something we believe is strengthened by our strong track record of conducting successful stem cell transplantation clinical trials for hemoglobin disorders.

4. Clinical research/cores proposed were not innovative and were perceived as currently supported by HRSA/Bill Young stem cell bill. Pre-clinical proposals were nnovative but not sufficiently well developed to proceed to a clinical trial in the near future; perhaps more appropriate in an Element Y application. We propose to construct a facility devoted to novel applications of stem cell transplantation for
hemoglobin disorders, not simply to construct a duplicate facility for housing cord blood collections from California families. This research would involve the collection of placentas for cryopreservation, analysis and mobilization of stem cell populations from placenta, and then processing these cells for use in a clinical transplantation trial that will be initiated in the next 1-2 years. We are currently preparing an IND with the FDA for this purpose. It is important to point out that the placenta-derived hematopoietic stem cells are the first new type of stem cell used in this field since the 1970’s, when cord blood was first used. Federal regulations governing this research have changed dramatically since that time, and are now far more complex. This project is thus truly innovative, and it will serve as a model for other attempts to use stem cells clinically. If proof of principle were provided by this initial clinical trial, the technology then would be applied to existing transplantation efforts, with the goal of expanding and improving outcomes after cord blood transplantation, particularly after unrelated donor transplantation. The proposed research is not supported by HRSA or the C. W. Young bill. The primary purpose of this bill is to establish cord blood banks and develop an inventory of 150,000 units for public use. It is not to perform clinical/translational research like that we have proposed. While a small amount of funds are allocated to support sibling banking ($250,000) by the funded cord blood banks, there are none in California who elected to participate in this sibling effort. It is critical that we have a facility for developing, characterizing, and distributing these cells for clinical transplantation trials. Thus, a GMP/GLP cell processing laboratory and a HLA laboratory are key components in support of the proposed clinical and pre-clinical investigations. This work cannot move forward without a facility.

5. A plan to utilize national networks in order to conduct a clinical trial was not detailed. It should be very clear from Dr. Walters’ track record that he is able to utilize, indeed currently is utilizing, such national networks in a highly productive fashion. The proposed pre-clinical investigations will be transitioned to phase I clinical trials in the very near term, responsive to the Element Z category we employed for this application. By providing proof of principle, this research has the potential to expand current clinical transplantation practice that will utilize HLA – mismatched and unrelated stem cell donors for hemoglobin disorders, a practice that is not routinely available. These will be conducted using multi-center networks that we can access for completing these clinical trials and which were detailed in the application. These include the Center for International Blood and Transplantation Research (IBMTR), the Sickle Cell Disease Clinical Research Network (SCD-CRN), and the Blood and Marrow Transplantation Clinical Trials Network. Our investigative team has leadership positions in these organizations and a successful track record of carrying out similar translational clinical trials in human hematopoietic cell transplantation.

We appreciate the opportunity to present our responses to critiques of our application and hope that the ICOC might look favorably on this and future applications to CIRM that we submit for consideration.

Respectfully,

Bertram H. Lubin, MD
President, Director of Medical Research
5700 Martin Luther King Jr. Way
Oakland, CA 94609

Mark Walters, MD
Director, Blood and Marrow Transplant Program
Children's Hospital & Research Center, Oakland
747 -52nd Street
Oakland, CA 94609

Coming Up

We have been tied up this afternoon with an interview with the new president of the California stem cell agency so we have fallen behind on some interesting events. However, we will post later this afternoon a copy of another letter from Childrens Hospital Oakland Research Institute seeking to reverse an unfavorable recommendation on its bid for a multimillion dollar lab construction grant. The letter is something that CIRM has refused to release. Also upcoming is an item on the 57 letters of intent, including 15 from business, for new cell line grants as well as a post on background information on the biotech loan program hearing tomorrow. For those of you who can't wait, just click on the links in the previous sentence to go straight to the CIRM documents.

Seeking Summaries: The Hunt for How $263 Million Will Be Spent

If you are looking for the public summaries of the applications for $263 million in stem cell lab construction grants scheduled to be considered tomorrow by the California stem cell agency, you will not find them on the meeting's agenda.

Instead they are tucked away under the category of "funding opportunities," although the opportunity to apply has long since passed.

Normally, the agenda for the Oversight Committee contains a link -- at some point prior to the actual meeting -- to the summaries of applications for grants. However, as of this writing, no link was posted on the CIRM website.

When we inquired early today, we were told that they can be found at the "funding opportunities" location. It wasn't clear when the summaries were posted at that location – perhaps Friday, perhaps Monday, we were told by the agency. A spokeswoman for the CIRM said she was going to ask about the reasons for failure to link the summaries to the agenda.

The simplest explanation is that there was a foul-up. Some might conjure up wilder reasons.

Whatever the reason, posting the summaries as late as Monday does not well serve the agency, the public or interested parties. State law requires ample notice in advance of public meetings because some governmental agencies in the past were not notifying the public about matters they were entitled to know. To serve the intent of law well, the agenda must also provide more than cryptic statements. Failure to provide background material well prior to meetings only leads to cynical speculation and creates an atmosphere of distrust.

CIRM had considerable problems in the past posting background material sufficiently in advance of meetings. Even Oversight Committee members complained. The problem seemed to ease a while back. But slippage, including the lab grants matter and also involving the biotech task force, has occurred recently. One would hope the problem will be resolved as the new president, Alan Trounson, settles in.

Zipped Lips and CIRM's $263 Million

A glittering array of 29 scientists and executives rule California's prodigious $3 billion stem cell research effort. In many ways, they constitute some of the finest minds in the business and have even included Nobel Prize winners.

The thinking was that this elite panel of experts could bring their knowledge and wisdom to bear on the world's largest funding effort for human embryonic stem cell research. But this week, many of them will remain mum as $263 million worth of decisions are made.

The group is formally known as the Independent Citizens Oversight Committee(ICOC). More commonly, it would be described as a board of directors for the California Institute for Regenerative Medicine(CIRM). On Wednesday and Thursday, the committee will make critical, initial decisions on handing out $263 million for lab construction at the Golden State's finest research institutions. But only about one out of three of the directors will be able to vote on or even discuss some of the key issues in what is the largest round of grants ever made by CIRM.

The reason? They are associated with institutions that are seeking big chunks of the $263 million jackpot. In many cases they have conflicts of interests that CIRM's attorneys say make it illegal for them to vote or even participate in debate.

The impact goes well beyond silencing most of the board on some matters. It could also create a "quartet majority" in which the votes of four persons could be all that is needed to take some actions. Here is how it could happen, based on Prop. 71, which created CIRM, and an explanation last August from Tamar Pachter, CIRM general counsel.

The strange situation stems from the requirement that many of the Oversight Committee members -- by Prop. 71 decree -- must come from institutions that stand to benefit from CIRM's largess. They include deans of medical schools and executives at the University of California and other academic and research institutions. In fact, of the 12 lab grant applicants that CIRM has publicly identified, 11 have one or more members on the ICOC.

Last summer Pachter told board members that when the time comes to allocate the $263 million into various "buckets" – parcelled out, in other words, into such categories of competition such as "CIRM institutes" and "CIRM centers of exellence" – only about 10 members of the ICOC would not have conflicts of interest. She said,

"They are members who work for for-profits, patient advocates who are unaffiliated with institutions who will be applying for funds. That's it."

She did not spell out the ultimate implications. But Prop. 71 uses the number of ICOC members eligible to vote as the basis for a quorum, rather than the total number of persons on the ICOC. Prop. 71 also states that a quorum is 65 percent of those eligible to vote. Action can be taken by a majority of a quorum. So when 10 persons are eligible to vote, the quorum is seven. A majority would be only four – a fact not directly discussed at the August ICOC meeting.

But Oswald Steward(see photo), chairman of the Reeve, Irvine Research Center at UC Irvine, is one ICOC member who was disturbed by impact of what Pachter had to say. He acknowledged the importance of the conflict of interest rules. But he added,

"A lot of us are going to be left out...It's not just the case we can't vote; we also can't even participate in the discussions. And I think that narrows the field of expertise in a way that is unfortunate."

The ICOC ran afoul of this problem in December when it approved adding $35 million to the lab grant program. Only eight persons on the board were permitted to participate in the debate on that proposal.

The "quartet majority" problem also leads to some interesting speculation about whether it could come into play in connection with the attempt by Childrens Hospital Oakland Research Institute to overturn an unfavorable decision by the Grants Working Group on its lab grant application.

Could the Oakland hospital's bid be approved by only four members of the ICOC? One could argue that ICOC members associated with institutions with competing grants could not vote on Oakland's request because it could affect the amount of funding available for their institutions. But before the Oakland bid can come to a vote, a member of the ICOC has to make a motion to approve it. Then Oakland has to line up three other sympathetic board members.

But it certainly is something that folks in Oakland could be thinking about as well as at the University of California at Riverside and Cedars-Sinai in Los Angeles, two other rejected applicants.

FTCR: Rejected Lab Grant Applicants Should Appeal in Public

A CIRM watchdog organization today urged five institutions "rejected" for multimillion dollar state lab construction grants to appear publicly next week and make their case for funding from the California stem cell agency.

John M. Simpson, stem cell project director of the Foundation for Taxpayer and Consumers Rights, said the review process for the $263 million lab grant program "has been flawed and smacks of favoritism that can only be cured by transparency." He said,

"CIRM management decided to reveal (last month) the 12 institutions that will be recommended for an invitation to seek funding so that they could use the information in year-end fundraising efforts. How is that fair to the five who were not anointed in secret by the closed scientific brotherhood?"

The California stem cell agency has declined to say whether any other lab grant applicants – besides Childrens Hospital Oakland Research Institute – are attempting to overturn negative decisions on their grant applications.

Ellen Rose, a spokeswoman for the agency, said,

"Appeals are allowable only if there is demonstrable evidence of a financial or scientific conflict of interest. Differences of scientific opinion among PIs and reviewers are not grounds for appeal. In the past, applicants who have raised questions about their grant applications or sought clarification, which is common in any granting exercise, have been informed of this policy. Thus far we have had no formal appeals to our grant-making process."

Simpson said CIRM's statement was "Orwellian double-speak." He said,

"I strongly urge representatives of all five rejected institutions to show up at next week's ICOC meeting and make their case in public directly to the board. It is, they claim, the decision making authority. What's happened so far were merely "recommendations.'"

By law, the Oversight Committee is the final authority on grant approval. It can accept or reject – for virtually any reason -- decisions by the working groups. That is one reason CIRM says it is not necessary for grant reviewers to publicly disclose their financial interests.

In response to queries from the California Stem Cell Report last month, two other institutions disclosed that their applications have been rejected. They are the University of California at Riverside and Cedars-Sinai in Los Angeles. However, they have not responded to queries on Thursday about whether they are asking Oversight Committee to reconsider the working group action.

The lab grant program is the first in which the names of applicants have been disclosed by CIRM, which previously said the names of all applicants were confidential even when the applicants themselves disclosed their own identity. The decision to assist the applicants with fundraising is important because CIRM will look more favorably during the two-step approval process on applicants with large matching funds.

The Oversight Committee is scheduled to take up the grants next Wednesday during the scientific portion of the approval process. Only those approved next week will move on to the next step.