Governmental Camels and Stem Cell Swag

Is it good business for a drug company to charge – let's say $47,000 for a 10-month cancer treatment – or will such pricing hurt the industry long term?

But forget the business issue. Is it good public policy to allow a company to charge those fees – labelled egregious by some? Especially if the treatment was partially financed with public funds?

Questions such as those stand close to the center of the debate over the intellectual property that will be produced by $3 billion in research funded by California's stem cell agency. Intellectual property policy is the vehicle because that's where CIRM sets its requirements for royalties and revenue-sharing connected to its research. That is also where it sets its requirements for affordable access to stem cell cures that it helps to finance.

The $47,000 treatment cost is not hypothetical. It involves Genentech and its drug, Avastin, which was developed with the help of some clinical trials that were subsidized by the federal government.

On March 15, the Wall Street Journal examined the case of Avastin in a front page story. Reporter Geeta Anand began her piece like this:

"Two years ago, Steven Harr urged Genentech Inc. to lower the price of a key drug that was helping buoy its stock price. He was an unlikely messenger because of his job: a Wall Street research analyst whose investing clients crave profits.

"In a conference room with 30 senior managers from the biotech company, Dr. Harr said he feared patients wouldn't be able to afford the drug Avastin, which costs about $47,000 for the average 10-month course of treatment for colorectal cancer. He warned that Congress 'will get involved when its constituents can't get drugs.' Genentech later capped Avastin's price, acknowledging the influence of Dr. Harr, among many others."

Harr also pointed out an interesting bit of blowback from oncologists detected during a survey he conducted. According to the WSJ story,

"He says most physicians surveyed weren't prescribing the drug in breast and lung cancer for fear of not being reimbursed. Avastin and Erbitux are given to patients intravenously in doctors' offices. Doctors buy the drug ahead of time, infuse it into patients and then wait to be reimbursed. Any refusal by insurers to reimburse would leave doctors thousands of dollars in debt."

Harr, an analyst with Morgan Stanley, sees high prices as bad for business.

"He says soaring cancer-drug prices, generating fat profit margins, aren't sustainable."

That is a message that is sometimes hard for business executives to accept. They rail at governmental fiddling with their enterprises. They froth at bumbling regulators. But at the same time, many seek government assistance for research, favorable regulation, tax benefits or laws restricting their competitors. Contrary to popular belief, the vast majority of legislative activity nationally and in California does not involve such things as gay marriage or sex offenders or drivers licenses. It involves "filthy lucre" and crass commerce. Most of it is instigated by those advocates of free markets – the top executives of the finest companies in America. It is why business spends tens of millions of dollars and more annually lobbying lawmakers.

Folks such as those at the California Healthcare Institute, which represents the state biomedical industry, want the grants from CIRM. But they don't want to pay the piper that provides the basis for the plenititude. Or they don't want to pay as much as some watchdog groups and legislators would like. But like any other investor, the state wants its slice and does not want to be treated a whole lot differently than, say, the venture capitalists at Kleiner Perkins Caufield & Byers, if they had laid out a $3 billion investment. When you invite governmental camels into your tent, it is sometimes hard to get them to leave.

Biotech, however, has valid points concerning writing what are basically the terms of a business deal into state law and regulation. Both are difficult to change and can impair development of cures if they are riddled with restrictive minutia. Likewise, biotech firms must see a strong likelihood of making money. If they don't, the cures will not be developed unless the government is ready to pay for the whole process, which is not likely to happen in our lifetime.

Obviously, the state of California is not a venture capital firm. Perhaps not so obviously, the stem cell industry is not the most shining example of private markets at work. The finest risk-takers in America(venture capitalists) run for the back exits, for the most part, when they see a stem cell executive come through the front door. The result is that with embryonic stem cell research in California, we have an amalgam of business, government and science. That means that compromises must be made by all the players. If one of the partners gets too greedy, the whole endeavor – the California stem cell experiment -- can fail.

Finally we should note that a group actively engaged with CIRM on IP issues was mentioned in the WSJ article but not by name. That organization is the Foundation for Taxpayer and Consumer Rights of Santa Monica, Ca. Here is what the WSJ wrote about FTCR.

"In the spring of last year, a taxpayer group in California began publicly condemning Genentech for charging too much for Avastin, noting that the federal government's National Institutes of Health had subsidized some clinical trials of the drug. Not long after, Genentech said it was considering capping the price of Avastin."

FTCR on Sacbee and Cha

John M. Simpson, stem cell project director of the Foundation for Taxpayer and Consumers Rights, sent along the following comment on today's Sacramento Bee editorial on CHA RMI.

"What the Foundation for Taxpayer and Consumer Rights has said is that there are enough red flags associated with CHA's leadership and corporate affiliations as to warrant a thorough vetting of an application from its researcher.

"Precisely because we raised our concerns, CIRM's staff is now on the record in public in response as promising a thorough review of all applications -- including this one -- before any checks are issued.

"We did our job. The editorial board of the Sacramento Bee did its job. Now it's up to CIRM to do its job."

See the item below on the Bee editorial.

Sacramento Bee: Fairness and Cha

The Sacramento Bee today said today that the California stem cell agency should "resist calls to rescind or freeze" a $2.6 million grant to CHA RMI, whose founding president is embroiled in an international plagiarism scandal.

The medical director of an allied organization, CHA Fertility, is also under investigation by the state Medical Board in connection with an allegation that he seduced her and lied to her about the number of eggs he extracted from her.

The Bee said in an editorial:

"Both allegations are serious. But the CHA scientist who applied for and received the $2.6 million stem cell grant, Dr. Jang-Won Lee, hasn't been implicated in either incident. Unless someone can demonstrate otherwise, the California Institute for Regenerative Medicine should resist calls to rescind or freeze the $2.6 million grant.

"The issue is a simple one of fairness. Over the years, medical scandals have rocked several university medical centers, including one at UC Irvine that was forced to close its transplant center. These revelations were shocking, but they don't mean that all scientists affiliated with UC Irvine should be disqualified from government research funds. Nor, by itself, should Lee's affiliation with CHA prevent him from receiving a state grant, which he hopes to use in the development of stem cells that can be used to study Amyotrophic Lateral Sclerosis, also known as Lou Gehrig's disease."

For more details on this issue, see: "CHA Example," "Grant Recipient." You can also use the "search blog" function at the upper left hand corner of this page to find all the items on CHA. Use the search term "Cha."

Stem Cell Snippets: Financial Challenges, Kuehl and Presidential Search

CIRM's Governance -- The stem cell institute's governance committee will meet April 5 in San Francisco to consider "CIRM merit and professional development programs," "key financial challenges and opportunities" and travel rules for the Oversight Committee. Public teleconferencing locations are available: Two different sites in Los Angeles, three different locations in San Francisco and separates at Stanford, Sacramento, La Jolla and UC Irvine.

Kuehl and the Mayor – State Sen. Sheila Kuehl, author of legislation to guarantee the state a return on its stem cell investment, is a member of Los Angeles Mayor Antonio Villaraigosa's inner circle, according to the Los Angeles Times. The story by Duke Helfand says the mayor has offered her a job more than once. She says she wants to be on the ride when he goes for governor.

CIRM Presidential Search – A meeting scheduled for today of the CIRM presidential search subcommittee has been cancelled. Do not expect fresh information until the April 10 Oversight Committee meeting in Sacramento.

More Response from CHA RMI

CHA RMI and its California stem cell grant surfaced on the web site of The Scientist magazine with more details about the company's response.

The report by Kirsten Weir contained the following:

"According to a statement released by CHA RMI, the organization was incorporated in California in 2005 and 'has been engaged in adult and embryonic stem cell research at its Los Angeles laboratory...None of the member companies belonging to CHA Health Systems have any ownership interest in CHA RMI and none of the companies have any voting rights on CHA RMI's Board.'

"According to the statement, Jang-Won Lee earned his PhD from the University of Connecticut and has held positions at Wake Forest Institute for Regenerative Medicine and Children's Hospital & Harvard Medical School. Lee could not be reached for comment."

Most of the other information in The Scientist report is familiar to readers of this web site.

Correction:

The SB771 item from last night (3/25/07) incorrectly said that the CIRM Oversight Committee was scheduled to meet April 11 in Sacramento. The meeting is actually scheduled for April 10.

LA Times Piece on CHA RMI Has Response from Researcher

The Los Angeles Times Monday ran its story concerning CHA RMI and its $2.6 million California stem cell grant, including a statement from the main researcher on the project.

The Times story was picked up the KNBC television station in Los Angeles, which did not add any new information to the account.

The Times piece by reporter Mary Engel began by noting that the grant went to a research center whose founding president is "embroiled in an international dispute over authorship of a medical journal article." Then it listed the ethical allegations concerning an associated fertility clinic.

Engel's story also had this from the researcher involved:

"In an e-mail to The Times, the lead scientist for the grant, Jang-Won Lee, said he was not involved in any of the allegations. The research, he said, will undergo thorough scientific and ethical review, and is aimed at developing therapies for a devastating neurodegenerative disease."

She also had this quote from John M. Simpson, stem cell project director for the Foundation for Consumer and Taxpayer Rights, concerning the secrecy involved in the grant review process.

"'Had everyone known that a grant was being discussed to that organization, things would have gone slower and questions would have been raised then.'"

We have a query into CHA for a response on the issues that have been raised and have promised that we will run it verbatim when we receive it.

For previous items on this see: "Grant Recipient," "Little Notice" and "CHA Example."

The SB771 Debate: White Knights vs. Greedy Big Pharma?

"Mom and Apple Pie" – that's one way to look at the latest legislation to step into the affairs of the uniquely independent California stem cell agency.

The bill is crafted in such a way that it is difficult to oppose. In other words, it is virtually a "motherhood" bill. After all, who can be against the state of California receiving a fair share of the perceived bountiful booty from the $3 billion in state-financed research? Oppose that and you can be tarred with the brush of greedy Big Pharma.

We are not talking about the details of SB771. That involves the nitty gritty of intellectual property, a daunting and dense subject for the media, not to mention your average reader. It is easier to cast this as battle between avaricious Big Business and the White Knights who protect the public. Lawmakers do not want to be seen as voting in favor of $100,000-a-year treatments that would not have existed without state-financed research.

Whether or not Sen. Sheila Kuehl, D-Santa Monica, and lead author of the bill will choose to play it that way, some of the other interests involved may do so. We cannot say what Kuehl's strategy is, but all accounts, she is a very smart woman (Harvard grad and former law professor) and politically astute. As chair of the Senate Health Committee and veteran activist and politico, she knows what it takes to succeed with legislation.

Previous legislation involving CIRM was more complex, giving more people more reasons to oppose it. That's not to minimize the complexity of Kuehl's measure, but at its heart it is quite simple – give the people of California a share and help out the ailing poor. Wasn't that the promise in the Prop. 71 campaign?

The opposition is likely to be led by the California Healthcare Institute, which represents the biomedical industry. The industry is not a minor player in the Capitol and can use its resources well. But it will have to step smartly to avoid being tagged as greedy.

The scenario begins to play out in the second week of April with the first hearing on the bill by the Health Committee on April 11, the day after the Oversight Committee of the stem cell institute meets in Sacramento. As part of the day's activities, members of the 29-member panel are expected to visit some legislators to discuss areas of mutual interest.

In a case of adroit timing, California stem cell chairman Robert Klein is scheduled to speak to the Sacramento Press Club on April 9, two days ahead of the April 11 hearing. CIRM has also scheduled its own hearing into IP issues on April 9 in Sacramento. We say adroit because Klein's talk and the hearing will help frame the issues in the media ahead of the Senate hearing, if the events are covered. That is a big if. IP is a boring news topic in the minds of most editors and reporters. CIRM issues are a third tier media matter at best in the Capitol. Witness the extremely light coverage of CIRM this past year with the rare exceptions of occasions when buckets of money were rolled out (grant approvals by the CIRM Oversight Committee). Arnold's contretempts with Rush are much higher on the California news agenda, although nearly meaningless.

With four stem cell events in one week in Sacramento, news editors are likely to cover one and not the rest. The earliest may get the media worm.

With a super, super-majority vote (70 percent) required in both houses, Kuehl's bill likely will find tough sledding. On March 16, in Los Angeles at the Oversight Committee meeting, we asked Assembly Speaker Fabian Nunez about the measure. He was there for a news conference touting CIRM's good works. But he said he knew nothing about Kuehl's bill. To win a 70 percent vote in the Assembly, he will have to know more.

For those of you interested in the real stuff of IP, CIRM has posted some advance material concerning its IP hearing April 9. Among the issues CIRM wants to address are the following:

"Is there a reference or scheme in another body of law that would provide a workable formula to price drugs purchased in California that have been developed with CIRM-funded patented inventions?

"What mechanisms exist that can be used to formulate the price of non-drug therapies provided to Californians?

"Is the term 'public funds' sufficiently precise to capture the universe of purchasers intended in the scope of regulation 100406?

"What comparables would be used by which the “access plans” referenced in regulations 100406 and 100408 be assessed?

Written comments may be submitted directly to CIRM if you are unable to attend the hearing.

Here are links to additional background on the legislation. "Tall Hurdle," "Open Kimono," "CIRM IP Legislation."

(Editor's note: An earlier version of this item said the Oversight Committee meeting was April 11. It is scheduled for April 10.)

CIRM Grant Oversight Question

Lawrence Ebert has posted the following question:

"Of the procedure on grants given by CIRM, I was wondering "who" has the authority to conduct oversight. Directly, this comes up as to "who" might have been responsible for vetting the Cha proposal. Down the road, "who" would conduct any investigation of alleged research impropriety. In a different research area, this issue is currently looming large. See
http://ipbiz.blogspot.com/2007/03/more-about-congress-reviewing-purdue.html

"Separately, how much of the CIRM grants are going directly to the conduct of research, and how much are going to overhead of the respective institutions?"

Here is what we know. Re the questions of oversight of grants given by CIRM, it is CIRM itself that has oversight and the agency vets the proposal and monitors its execution. It is unclear who might conduct an investigation of research impropriety beyond CIRM, although the state Department of Justice has wide authority to investigate and prosecute violations of state law. CIRM's research regulations have the force of law.

We can't tell you the split on overhead vs. actual research, but we learned at the March 15 meeting of the Oversight Committee that comparing size of NIH grants and CIRMs for the same project is not accurate. CIRM grants apparently include funds that are not usually included in the announced figures for equivalent NIH grants.

Fresh Comment.1

Lawrence Ebert is onboard with a comment on the correction below and is a little puzzled. We have posted an comment/explanation that should clarify the matter. John Simpson has a comment on the "CHA Example" item. An anonymous comment has been posted on the "Plagiarism, prayer" item.

Fresh Comments

Jonathan Eisen has posted a new comment on the "CHA Example" item below in which he proposes a Journal of Rejected Grant Proposals. We suspect his suggestion is a bit tongue in cheek, but he makes some interesting points. Also new is an anonymous comment on the "Plagiarism, Prayer" item that involves a patent matter and Cha.

Correction

On Friday March 23, we incorrectly reported that the California Stem Cell Report was the first to pull together the plagiarism allegations and other ethical concerns involving CHA RMI and its allied organizations and link it to the CIRM grant. In fact, the Bodyhack blog on Wired.com carried much of the same information on March 17. We simply missed their earlier report. Our apologies to the folks at Bodyhack, particularly Steve Edwards, who wrote the March 17 item.

Fresh Comments

Jonathan Eisen has posted a comment on the "CHA Example" item below. We have posted a response to his comment. Click on the word "comments" at the end of the item to see the little pearls.

The WSJ, Bile and the Wind

Christopher Thomas Scott, the executive director of the Program on Stem Cells in Society at Stanford, sent the following along. He wrote it in the form of a letter to the editor after reading an op-ed piece on embryonic stem cell research in the Wall Street Journal last week.

"Dear Editors:

"It was familiar a twist in the gut. Robert George and Thomas Berg's "Six Stem Cell Facts" (March 14 Wall Street Journal) provoked the usual response: Should I write 1) a trenchant rejoinder (Six Stem Cell Lies) 2) a carefully crafted counter argument, or 3) lie in wait and pounce in the pages of another newspaper?

"I was up Thursday before dawn. I poured myself a cold, frothy tumbler of bile, and sat down to write.

"Nothing happened.

"I was mystified--George and Berg's essay was an easy target, trotting out old moral and religious tropes.

"It took me a few days to figure it out, but now I understand this odd ennui. Supporters of embryonic stem cell research, including those of us who battle in journals and newspapers, have moved on. Embryonic stem cell research has left the barn, as the saying goes, and now we're getting on with the important stuff--the business of discovery, treatments and cures--what America does better than any other.

"This leaves commentators like George, Berg, and Krauthammer all alone, caterwauling and swinging roundhouses into thin air. The ringside seats are nearly empty. The images of dismemberment (as if an itoa of cells has arms and legs) or Krauthammer's lovely description in sanctioned government reports of "fetuses hanging on meathooks" has become a rhetorical sideshow, better suited for circus barkers. Will they join us at the edge of medicine's most promising frontier, where new, nuanced debates about stem cell therapies are taking shape? Or will they remain behind, shouting into the wind?"

RHA RMI Issues Receive Little Notice in Media

The flap over the $2.6 million California stem cell grant to a Los Angeles enterprise linked to ethical lapses involving a Korean scientist received scant attention today in California newspapers.

Only one story appeared in a newspaper, and one online. Neither contained much new information. Reporter Carl Hall of the San Francisco Chronicle did carry a comment from CHA Health Systems, the parent company for CHA Regenerative Medicine Institute, which was approved for the grant last week by the CIRM Oversight Committee. Hall wrote:

"Jason Booth, a spokesman in Los Angeles for CHA Health Systems, said the research unit is a bona fide California nonprofit whose status was not at issue, and that its 'grant was based on a thorough scientific review that speaks for itself.'"

Rob Waters of Bloomberg.com, who was the first to point out the connection between CHA Health Systems and CHA RMI, also reported on the calls for an investigation. He said a representative of CHA in Korea said the company would respond later.

The Californa stem cell agency said it was in the process of conducting a routine review of all the grants approved last week, which will include an examination of whether each recipient is eligible for the award. Waters quoted the agency as saying that the review could take six weeks.

The Bodyhack blog on Wired.com was the first (on March 17) to pull together the plagiarism allegations involving the head of CHA Health Systems along with other ethical concerns involving CHA and point out that a CHA subsidiary had been approved for the $2.6 million state grant. The California Stem Cell Report on the matter appeared Wednesday night and led to the calls for the investigation.

We have emailed CHA several times seeking a comment on the matter, including a promise to run their comments verbatim. We will do so when we receive a response.

(Editor's note: An earlier version of this story incorrectly said that the California Stem Cell Report was the first to link the CIRM grant and the ethical concerns involving CHA.)

Fresh Comment Update

Jonathan Eisen has added more commentary on the openness of the CIRM grant system. See "comments" on "Sunburn" below. Lawrence Ebert has more on the issue of "hidden economic interests" in New Jersey research. See "Fresh Comments" below.

As a point of information, we have started these comments advisories in an effort to bring more attention to the contributions of those who take the time to add to this dialogue. These manual comment updates are a bit clunky but we are looking for a sleek, hotsy-totsy way of providing them automatically in a separate space on this page. If you have any suggestions for finding a nifty HTML tool that will do that, send it along. Meanwhile, as general guidance, it would be better to post comments on the items dealing with the subject matter as opposed to posting them on these advisories on comments being posted.

Keep the stuff coming. Thanks to all.

Advisory

The press release by the Center for Genetics and Society concerning the CHA grant has now been posted on its web site. Here is the location.

The CHA Example: How CIRM Decides Who Gets the Big Bucks

The $2.6 million California stem cell grant involving the CHA Regenerative Medicine Institute received a score of 77 from a panel of grant reviewers, although they commented that it "can be easily qualified as overly ambitious."

Approval of the application last week by the Oversight Committee of the California Institute for Regenerative Medicine has resulted in calls for an investigation into CHA RMI's nonprofit status and its links to a Korean scientist involved in an international plagiarism case, among other things.

The CHA application first came up for a review last January by a CIRM working group, chaired by Stuart Orkin of the Dana Farber Cancer Institute. Fourteen other scientists held seats on the group. Seven members of the Oversight Committee sat on the panel. Only one is from Los Angeles, where CHA RMI has its office. It is not known whether she was in attendance when the CHA application was discussed. All of the scientists are from out-of-state.

Meeting privately, the reviewers recommended the CHA application and others for funding. The CHA application was placed in the first tier of grants that were sent on to the Oversight Committee. The scores of the first tier grants ranged from 95 to 66. The reviewers received detailed information on the proposal, including the names of the principal researcher as well as its methodology. Only one reviewer was recused from considering the grant. He was Jeffrey Rothstein of John Hopkins, who works in ALS research, a field that was also targeted by the grant.

Prior to action by the Oversight Committee, the names of all CIRM grant applicants and their institutions are secret except during the private meetings of reviewers, according to CIRM policies. The Oversight Committee is also not told their names during the votes on the reviewers' recommendations. The names of the winning applicants are only disclosed after the vote. The names of the losers will never be disclosed by CIRM.

CIRM says its secrecy is justified for a number of reasons. The agency says it is the traditional way grant applications are handled in the scientific community. It is professionally damaging, CIRM also says, for scientists to be publicly identified as not being able to win grants. It is also damaging to be criticized in public. Maintaining secrecy means that scientists are more likely to propose more ambitious and riskier research than would otherwise be the case. The results of science will be better in the aggregate, thus benefitting the public more than would identifying the applicants and their institutions, CIRM says.

During last week's Oversight Committee meetings when the grants were approved, the 29 members of that panel were not told the names of the applicants or the institutions. They were given a summary that is also available to the public. Individual members were given a list of the grants by number on which they could not vote or participate in the debate. Those lists were withheld from the public at the meeting. Just prior to voting on or discussing an individual grant, a list was read of the committee members who could not participate in the debate. At that point, well-informed members of the audience and probably many members of the committee could identify the actual institutions involved and often the individual researchers. The persons who could not are ones who are not as well informed on stem cell research.

The Oversight Committee voted on the first tier of grants as a block. At that point, no list of recused members was read to the public. Rather each member announced that they were voting in favor of the block with exception of grants where they had a conflict. CIRM's outside counsel recommended the procedure.

Following the vote, CIRM posted a list on the Internet of Oversight Committee members recused from voting on the CHA grant. They are Ricardo Azziz, chair of Department of Obstetrics and Gynecology at Cedars-Sinai in Los Angeles, Jeanne Fontana, a surrogate for John Reed, head of the Burnham Institute in La Jolla, and Richard Murphy, president of the Salk Institute, also in the La Jolla area. Reasons for their recusal were not posted.

(The California Stem Cell Report has argued often against much of the secrecy in the grant-making process for a variety of reasons. We will write more about the issue later.)

In response to a query, Dale Carlson, chief communications officer for CIRM, supplied the following:

"The CIRM grant review and administration process does not end with the ICOC's vote on deciding which applications to approve or not approve for funding. To that point, the review process by the Grants Working Group is focused on scientific merit. After that, there is an internal administrative review by Institute staff to ensure that each approved application is from an institution and principal investigator that meet the eligibility requirements of the specific Request for Applications (RFA); of the requested budget and proposed facilities for the proposed project; and of the institution's mechanisms for complying with our grants administration policy and medical and ethical standards.

"The administrative review process can take several weeks (we are still working on the SEED grants approved in mid-February, for example) and only after it's completed to our satisfaction do Notice of Grant Awards (NGAs) go out to recipient institutions and researchers. Checks follow NGAs.

"The NIH grants review process is similar."

The principal investigator on the CHI RMI grant is Jang-Won Lee. Little information is available about him on the CIRM web site. Carlson said the score of 77 on his grant is an average of each score by each reviewer. Here are the rankings of the grants.

Below is the text of the strengths and weaknesses of his application based on the CIRM reviewers assessment. More information on the grant can be found at this location.

"STRENGTHS: The proposal is well-written and includes preliminary data in pigs and novel methods. The research plan is nicely developed and the PI has the appropriate expertise, at least in animal cloning (less with hESCs), to be successful in this endeavor. Success of the PI in the porcine model adds strength to the plan. A large collection of letters of support provides evidence of enthusiastic collaboration with the PI that will add critically needed expertise to the project. The plan to differentiate and transplant hESC-derived neural cells in a well-established mouse model with experts in the field strengthens the lack of experience with hESC culture (but not derivation) by the rest of the group.

"WEAKNESSES: This is a proposal that can be easily qualified as overly ambitious. The author provides a shopping list of all the experiments that will happen after the ALS SCNT embryos have successfully been established and characterized. This seems premature. The proposal would be successful if the derivation is first done accurately and convincingly to generate a handful of lines that will be available for the community. Preliminary data on enucleation, SCNT and hESC derivation in an animal model should be done before proposing these studies. Specifically, SCNT on frozen oocytes in an animal model should be done before using completely viable, clinically useful human oocytes. The use of frozen oocytes for SCNT has not been established, and is likely to be a significant technical problem for enucleation and whole cell injection. There is no indication of a plan to enucleate the oocytes in the proposal and a clear rationale for using one or both of the methods used previously by the collaborator who developed the method is required. A plan for the derivation of hESCs is also needed along with a rationale for the use of ALS cells for tranplantation studies, rather than normal cells. It also appears that no one on this project has experience with this hESC derivation, or the derivation of any ESC lines.

"The section on clinical grade ESCs is not necessary for the proposal and should be removed. These ESCs are not stable lines that have been shown to be maintained in vitro. In fact, they appear by the literature and preliminary data to be a mixture of hESCs and hESC-derived differentiated populations. The plans to differentiate hESCs for transplantation do not require this intermediate step. It is unfortunate, because the application of novel SCNT techniques is a reasonable way to move the field of SCNT and hESC biology forward. If the rest of the proposal was as well-designed as the pig studies, the score would be very high."

CGS: CIRM Grant Recipient Has 'Shadowed' History

The Center for Genetics and Society today said "troubling questions" have arisen in connection with California's $2.6 million stem cell research grant to CHA RMI, adding another voice to the call for an investigation.

Marcy Darnovsky, associate director of the Oakland-based center, said in a press release:

"The leadership of CHA Health Systems (a Korean firm) has a shadowed recent history, including a lawsuit that alleges the director of its fertility center lied in order to obtain a woman’s eggs, The CIRM needs to live up to its oft-stated commitments to transparency and responsibility by freezing this multi-million dollar award while a thorough investigation is undertaken. If questions cannot be satisfactorily answered, the grant should be rescinded.”

Jesse Reynolds, a policy analyst at CGS and who has attended many CIRM meetings, said:

"Did CHA Health Systems establish this subsidiary in order to pursue California public funding, at a time when South Korea government funds were unavailable because of the Hwang Woo Suk cloning scandal? Given the recent record of unethical conduct in this field, the CIRM should have known to exercise greater scrutiny."

The press release continued:

"The medical director of the CHA Fertility Center is the subject of a lawsuit filed by a woman who says that he lied about the number of eggs that had been collected from her, causing her to continue seeking treatment from him. The CHA Fertility Center and the CHA Regenerative Medicine Institute are located in the same Los Angeles office building.

"'The lawsuit suggests that CHA’s leadership placed a woman at unnecessary risk by misleading her into undergoing repeated cycles of egg retrieval,' Darnovsky said. 'Women’s health advocates have warned about the health risks of egg retrieval, as well as about likely conflicts of interest between fertility doctors conducting egg retrieval and researchers who want the eggs for their experiments.'"

Asked for a comment, Dale Carlson, chief communications officer for CIRM, said CGS' comments were "another uninformed reaction." He used similar language concerning statements by the Foundation for Taxpayer and Consumers Rights.

We have asked CHA for comment on these matters and will carry them when we receive them.

The center's press release was not posted on the Internet at the time of this writing. We will carry an advisory when it is posted.

FTCR Calls for Investigation Into California Stem Cell Grant

A California watchdog group has asked the state's stem cell research agency to investigate a Korean-linked organization that the agency approved last week for a $2.6 million grant.

John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumers Rights, said in a press release that CIRM's "secretive awards process let a questionable $2.6 million grant slip by the Oversight Committee without adequate scrutiny."

His comment came today following a report Wednesday on the California Stem Cell Report concerning the recipient of the grant, CHA RMI, and Kwang-Yul Cha, chief executive of the parent company of CHA RMI.

In a letter to the CIRM, Simpson said:

"It is not clear what (CHA RMI's) affiliation is with its corporate parents CHA Medical, CHA Biotech and other corporate for-profit entities. Kwang-Yul Cha is the chief executive of CHA Health Systems, chairman of Hollywood Presbyterian Medical Center and director of CHA Regenerative Medicine Institute. Is CHA RMI truly a non-profit institution eligible for funding in this round of grants?"

Simpson also said "serious questions" have been raised about Cha in connection with plagiarism allegations along with a state inquiry into whether he was violating the law by using MD after his name when he is not licensed to practice medicine in California.

Simpson said in the press release:

"We’ve argued that the process should be open and the applicants identified as they do in Connecticut. The stem cell institute refused to let the sun shine in and they got burned as a result."

In response to our query, Dale Carlson, chief communications officer for CIRM, said,

"Simpson appears to be uninformed about the grant review process, here and at other agencies."

We have asked Cha for a comment and will carry it when we receive it.

Simpson also said,

"I'm grateful the California Stem Cell Report first linked the CHA Regenerative Medicine Institute to the problems in its affiliates. Without David Jensen's digging this would likely have slipped by us all."

More on Plagiarism, Prayer and Cha

Patent attorney Lawrence Ebert has posted details concerning Kwang-Yul Cha, whose subsidiary has won a $2.6 million California stem cell grant, and Cha's "anonymous prayer" paper in The Journal of Reproductive Medicine.

Writing on his Ipbiz site, Ebert said:

"One co-author is a convicted felon, one co-author has had his name removed, but JRM won't retract it."

Ebert also had more details on the plagiarism issue from The Scientist magazine.

"Fertility and Sterility has censured the authors(including Cha) of a 2005 article after learning a Korean journal had published the identical paper one year earlier. The Fertility and Sterility authors also left off the name of Jeong-Hwan Kim, who was listed as the first author on the Korean paper and performed the bulk of the research reported in both papers."

The Scientist piece continued:

"The journal will also issue a note in an upcoming issue describing the transgression, and has barred every author listed on the original Fertility and Sterility paper from contributing papers to the journal for three years, editor Alan DeCherney told The Scientist. 'This is a serious punishment.'"

Fresh Comments

Lawrence Ebert has posted a new comment on the CHA item below. "Faye" has posted a comment on "hidden economic interests" on the "Fresh Comment" post from 3/20/07.

CIRM Grant Recipient Tied to Korean Scientist Involved in Plagiarism Controversy

A Los Angeles organization that is scheduled to receive a $2.6 million research grant from the California stem cell agency is a subsidiary of a Korean enterprise headed by a scientist who is enmeshed in an international plagiarism dispute.

The scientist is Kwang-Yul Cha, who also "came under criticism a few years ago for his involvement in a study suggesting that anonymous prayers from strangers might double a woman's chances of fertility," according to the Los Angeles Times.

His firm, CHA Health Systems, is the parent company of CHA Regenerative Medicine Institute (CHA RMI) of Los Angeles, a non-profit organization that last week was awarded the research grant by the Oversight Committee of the California Institute for Regenerative Medicine. The funds were approved by the 29-member committee with no specific discussion of the CHA grant. The names of the organizations were not disclosed until hours after the vote.

The information about Cha's background was first published in the Los Angeles Times Feb. 18, nearly a month before the grant was approved. The story by Charles Ornstein said Cha, whose firm also owns Hollywood Presbyterian Medical Center,

"...is listed as the primary author on a medical paper that appeared in December 2005 in the U.S. medical journal Fertility and Sterility.

"But that paper appears to be nearly a paragraph-for-paragraph, chart-for-chart copy of a junior researcher's doctoral thesis, which appeared in a Korean medical journal nearly two years earlier, according to a Times review of both papers and the findings of a Korean medical society.

"Cha has denied any wrongdoing."

Ornstein continued:

"Cha also appears to be violating state law by using MD after his name on websites and in news releases in California. He is not licensed to practice in the state, records show. His resume says he received his medical training in South Korea.

"'We don't believe it's lawful for him to hold himself out in this manner,' said Candis Cohen, a spokeswoman for the Medical Board of California."

On Feb. 28, Ornstein also reported that Thomas Kim, the medical director of another CHA organization, the CHA Fertility Center in Los Angeles, was under investigation by the state Medical Board "over a patient's allegations that the doctor seduced her into a lengthy sexual relationship and then lied to her about her treatment." Kim's lawyer has denied he did anything wrong and said that it was a consensual personal relationship involving Kim and the woman.

We have queried both CIRM and CHA's organization in Korea for a comment and will carry them when we receive them.

Responding to a query from the California Stem Cell Report, John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumers Rights in Santa Monica, said:

"It strikes me that there are enough doubts about the credibility of the leadership of the CHA Medical Group so as to warrant a serious investigation before any money is transferred to its researchers.

"First, CIRM ought to determine the relationship between the for-profit corporate parent and the non-profit CHA Regenerative Medicine Institute. It's not at all clear that CHA Regenerative Medicine is truly a non-profit organization.

"Second, the CHA Biotech website says that the institute has received approval from the Western Institutional Review Board for stem cell research involving frozen human eggs. Under CIRM rules there needs also to be approval by a SCRO committee -- Stem Cell Review Oversight committee. It's not clear that has happened. It's also important to know the source of the frozen eggs."

"Given the track record of CHA's leadership, I'd say CIRM needs to ask some tough questions and not release funds until there is a satisfactory public explanation of what's going on."

The grant to CHA RMI was part of a package that was voted on last Thursday night as a block. They had been recommended for approval by a group of out-of-state scientists and some members of the Oversight Committee, who together privately reviewed the grants some time ago. But the names of the applicants and their institutions were withheld from other members of the Oversight Committee and the public when they came up for the final vote. The Oversight Committee includes the deans of both the UCLA andUSC medical schools as well as a member of the board of the Cedars-Sinai Medical Center in Los Angeles, where the committee's meeting took place. Other prominent California medical school deans also sit on the Oversight Committee.

The Los Angeles Times carried a brief story on the grants, mentioning CHA by name but with no further background. Both Los Angeles Mayor Antonio Villaraigosa and California State Assembly Speaker Fabian Nunez hailed the grants generally at a news conference, but did not mention CHA specifically.

The CIRM grants are subject to administrative review before the checks go out. That includes the legal standing of applicant institutions, the status of the principal research investigators, among other things.

Fresh Comment

Jonathan Eisen has just posted a comment on the "Sunburn" item below. Click on "comment" at the end of the Sunburn posting to view Eisen's remarks.

Nature Warns of Sunburn; UC Davis Scientist Warns of Hidden Agendas

Amidst the hoopla about the latest research giveaway by the California stem cell agency, a couple of news items popped up that dealt with openness and conflicts of interests.

Last week Nature magazine editorialized that CIRM was amply open. And on Sunday, the agency itself disputed a Sacramento Bee editorial that suggested CIRM is "on thin legal ice" because it does not require its grant reviewers to publicly disclose their financial interests. But first the Nature editorial, which ironically is not accessible to the general public. It says, among other things,

"Calls for yet more openness may be well intentioned, but they threaten to override the element of confidentiality that is inherent to fair peer review, and to undercut the agency’s mission of supporting cutting-edge research from the best Californian scientists. There comes a point at which yet more sunshine leads to sunburn."

Nature also said that requiring identification of those who do not receive grants

"...would be akin to the state of California publicly releasing information on all the job applications it receives, complete with adverse comments made during the hiring process. "

We could not disagree more. Seeking millions of dollars in state funds with no promise of economic return, which is what the research grants are all about, is fundamentally different than applying for a position as a state park ranger.

Stuart Leavenworth, an associate editor at The Sacramento Bee, noted in an email to the California Stem Cell Report that the magazine's position did not surprise him "given that Nature has steadfastly refused to disclose the conflicts of interest of its authors, unlike other journals." He pointed to statements by the Center in the Public Interest and more than 30 scientists that Nature does not "reliably" disclose its authors' financial ties to drug and biotechnology companies.

The Nature editorial also surfaced on the "egghead" blog at UC Davis.
Jonathan Eisen, a professor at the UC Davis Genome Center, said, in part:

"While I can see (Nature's) points, I am not sure they are the most objective place to look for for ideas on this issue. The question to me is not whether too much sunshine MIGHT cause sunburn it is whether just the risk of sunburn is worth keeping things closed. I think in this case I probably agree that the review of these proposals might be changed if it were an open review system. But as someone who has served on many grant review panels, I know that there are ALL sorts of hidden agendas that play out in the review. If review were completely open, at least these hidden agendas would be exposed to the world. Yes, some reviewers might be too timid in their reviews, but this openness would eliminate so many other problems inherent in anonymous review. This is why there are a few journals out there that now have open review of papers — something I think is certainly worth testing out."

Dale Carlson, chief communications officer for CIRM, wrote the op-ed piece that challenged The Bee's position. He said that grants are not in jeopardy and that two courts have upheld the legality of CIRM's actions. Carlson referred to lawsuits that that have unsuccessfully challenged the constitutionality of the agency.

With all due respect, we suggest that the key issue has not been fully litigated. At the time of the trial cited by Carlson, CIRM had only made a small number of grants. A track record simply did not exist on whether the grant reviewers were making de facto decisions. There is no doubt, however, that the Oversight Committee has final authority on making grants.

The fundamental question about public disclosure of the financial interests of the grant reviewers concerns good public policy and openness. Should the public should be allowed to know the financial interests of those who recommend that millions of public dollars be handed out to scientists? Along with that goes the question of whether the public should be allowed to know the names of persons and institutions seeking millions of dollars in research grants.

Our position is that the interests of the science community come after the interests of the public. Unwarranted secrecy in the grant-making process only feeds suspicion and creates the possibility of insider dealings, which are not likely to be healthy for science or stem cell cures. As Eisen notes above, hidden agendas can often come into play.

(Editor's note: If you are interested in the full text of the Nature editorial, please send us a note at djensen@californiastemcellreport.com.)

Zerhouni to Bush: Nation Better Served Without Research Restrictions

The head of the National Institutes of Health, an appointee of President Bush, today defied his boss and said the president's policy on embryonic stem cell research was ill-serving the nation.

The statement came from Elias Zerhouni and was reported by Angela Zimm and Neil Roland on Bloomberg.com. They covered a Senate hearing on funding for the NIH. They wrote that Zerhouni said:

"The current lines will not be sufficient. It's not possible for me to see how we can sustain the momentum of research."

Zerhouni continued:

"It's clear that American science and the nation will be better served if we have access to more cell lines."

According to Bloomberg, this is the context of the remarks.

"Senator Tom Harkin, an Iowa Democrat, asked Zerhouni, whether lifting the restrictions would have an effect on finding new cures.

"'The answer is yes,' Zerhouni said. The exchange came at a hearing of the Senate Appropriations subcommittee on Labor, Health and Human Services and Education."

Zerhouni could have said the same thing several years ago. But Bush is now a clearly a lame duck and on the ropes with the American public. And Zerhouni has his own future to consider. Being a handmaiden to Bush's stem cell policy is not the best position for someone who may be casting about for a new line of work.

Beyond $131 Million: Looking Ahead at CIRM

You could call it the pipeline and presidency issue. Even before the directors of California's stem cell agency approved an unprecedented $75 million in grants, some of them were worrying about what happens next.

Brian Henderson, dean of the USC medical school, told his fellow members on the CIRM Oversight Committee, "We do not want to congratulate ourselves too much."

CIRM, however, does have something to congratulate itself about, as Los Angeles Mayor Antonio Villaraigosa reminded them during a Friday morning news conference. "Put a smile on your face," he said.

CIRM has pumped out $131 million in grants so far this year, making it clearly the largest single source of embryonic stem cell research funding in the world. More millions will come later this year. And before the end of the year, with a little luck, they will see even bigger bucks flowing in through the sale of state bonds that have been delayed because of litigation.

However, the 22-member staff of the agency has been working extraordinarily long hours. "Heroic" was a word that came up often during last week's two-day meetings to describe the work of the staff. One example that was cited was the case of one staffer, who was up until 4 a.m. readying documents for the first day of the meetings. While that may be a tad exceptional, Oversight Committee members for some time have expressed concern about the workload of the agency.

As Michael Friedman, president of the City of Hope, put it last week, the agency has been sprinting, and "we are in for a marathon."

The "challenges" facing CIRM include the loss of President Zach Hall in June, the search for his successor, the void until the new president comes aboard and the need to fill the pipeline with more grants as well as administering the ones already approved.

Several board members said momentum needs to be maintained to provide opportunities for the new scientists that have been arriving in California to tap CIRM's $3 billion research effort. They urged Hall to fill staff positions as rapidly as possible to maintain the workflow. "Please don't scrimp," Friedman said.

CIRM is not likely to have a new president on board by the time Hall leaves, which will accentuate the normal uncertainty that arises with the arrival of new CEOs, especially in small, new organizations. However, something of a model exists for working through that period. Hall will take a vacation this month and has designated two persons to act in his stead, Arlene Chiu, scientific program director, on scientific matters and Lorraine Hoffman, chief financial officer, on other issues. How they fulfill their responsibilities will be a good test for June and later in the summer.

The 29 members of the Oversight Committee hold an important key to CIRM stability and momentum. They should curb their micro-management urges, some of which are possessed in abundance by some members of the board, and focus on filling the presidency as quickly as possible. Twenty-nine busy fingers in the CIRM pie are likely to leave a pretty mess.

Henderson and the others are right to worry about a letdown, which can easily happen during or following periods of intense effort, which has been the story since January 2005. Avoiding a letdown and leaving a healthy organization may be one of Hall's most important tasks in the next few months. But much of the burden will fall on senior CIRM management, the folks who will ride through the transition. After all, they are the ones who will be left to engineer the giveaway of a piddling $2.8 billion or so over the next 10 years.

Telling Tales and Salvation

It has not exactly been the tales of "1,001 Arabian Nights." But last week we did post our 1,001st item on the California Stem Cell Report.

Scheherezade, the narrator of "The Book of One Thousand and One Nights," spun her stories to avoid being executed by the evil Sultan. As she put it, "Is it possible that by telling these tales, one might indeed save one's self."

However, in the case of the 1,001 stories on the California Stem Cell Report, I am more reminded of the saying about the talking dog. So what if he talks, what does he have to say?

That is a matter for all of you -- our much-appreciated readers -- to determine. Cheers to you all.

Grant Coverage Light, Bloomberg Highlights Korean-linked Award

The announcement of nearly $76 million in embryonic stem cell research grants in California generated modest media attention today – less than last month's giveaway that involved much less money. The presence of Gov. Arnold Schwarzenegger, however, helped push the coverage of February's awards to an exceptional level. Plus they were the first awarded by CIRM.

Few surprises popped up in the papers today. But reporter Rob Waters of Bloomberg.com highlighted the Korean connections of one Los Angeles-based recipient. Waters wrote:

"CHA RMI was awarded a grant of $2.6 million. Along with its sister organization, CHA Stem Cell Institute in Seoul, it's a non-profit unit of CHA Biotech(of Seoul). The Los Angeles unit proposes to use its grant to create stem cell lines using a process known as therapeutic cloning, or somatic cell nuclear transfer.

"The CHA RMI researchers will attempt to create cloned human embryos with the cellular attributes of Lou Gehrig's disease, an incurable neurological disorder. They will try to do this by combining human egg cells whose nucleus has been removed with DNA provided by adults with the disease. The scientists will then isolate and extract stem cells from the embryos.

"'We feel a great responsibility for this project and we will pursue our research with utmost efforts,' Chung Hyung Min, a professor and the director of the project at CHA Stem Cell Institute, said in a telephone interview from Seoul. "It won't be an easy project, but we're striving so that our efforts can contribute to curing Lou Gehrig's disease and many other diseases such as Parkinson's disease."

"CHA Biotech is a for-profit entity set up to coordinate the work of academic researchers and hospital physicians centered on stem cell, gene therapy and regenerative medicine technology, according to its Web site. It's part of CHA Health Systems, also called the CHA Medical Group, which owns or is affiliated with several universities, hospitals and research institutes in Korea and the U.S."

Prop. 71 limits grants to institutions located in California, which CHA RMI appears to be. We are attempting to track down a more detailed definition of the limitation and will post it when it becomes available.

Most reporters focused on the dollars in the grants. But Jim Downing of The Sacramento Bee zeroed in on the researchers and their goals. The first two paragraphs of his story read:

"Mark Zern is trying to figure out how to grow adult human livers, more or less from scratch.

"Alice Tarantal hopes to find a way to regenerate failed kidneys."

Here are links to other stories and press releases issued by recipient institutions. We will carry links to other news releases from recipients as they come to our attention.

Steve Johnson, San Jose Mercury News

Carl Hall, San Francisco Chronicle

Reporter Terri Somers, San Diego Union-Tribune

Mary Engel, Los Angeles Times

Gary Robbins, Orange Country Register

People's Daily Online

UCLA

UC San Diego

UC San Francisco

Burnham Institute

Stanford

Grant Press Release Now on CIRM Web Site

The news release on the CIRM grants is now available on its web site so you don't have fight your way through the formating issues in the item below. Here is the link.

CIRM Press Release on the Latest Grants

The following is the complete press release on the latest grants from CIRM. It should be posted shortly on the CIRM. We are posting it here because of a delay in the posting.

----------

For release: IMMEDIATE Contact: Dale A. Carlson

415/396-9117





$75 MLLION BOOST FOR CALIFORNIA STEM CELL SCIENTISTS



Assembly Speaker says California on the path to cures



State now largest source of funding for embryonic stem cell research



LOS ANGELES, March 16, 2007 – Just a month after approving nearly $45 million for embryonic stem cell research, California’s stem cell agency authorized another $75.7 million in additional funds for established scientists at 12 non-profit and academic institutions.



The 29-member Independent Citizens Oversight Committee (ICOC), governing board of the California Institute for Regenerative Medicine (CIRM), today approved 29 Comprehensive Research Grants for approximately $74.6 million over four years, to accomplished stem cell investigators at academic and non-profit research centers throughout the state. The grants were selected from 70 applications from researchers at 23 institutions, who sought more than $175 million in CIRM funding.

“This time of the year new life and new hope seem to be everywhere you look,” said Fabian Núñez, Speaker of the California State Assembly. “With these new grants, California is continuing on the path of turning the hope and promise of stem cell research into the reality of therapies and cures for millions of Californians and people across the globe. The California spirit – the perseverance, creativity and resourcefulness that has made us a leader on everything from gold mining in the 19th Century to fighting global warming in this one -- is fully present in our stem cell research teams. With today’s grants California shows we are again blazing the trail.”

Speaker Núñez joined Los Angeles Mayor Antonio Villaraigosa and Robert N. Klein, chairman of the ICOC, at a press conference to review the latest research grants.

“As of today, California is the largest and most stable source of funding for human embryonic stem cell research in the world,” Klein said. “The scientific projects proposed for our third set of grants are very strong, and it’s clear that there is an abundance of scientific opportunities for the state’s investments. We are off to an extraordinary start towards fulfilling the mandate of 7 million California voters, and the hopes of patients and families worldwide.”

The Comprehensive Grants approved today will support mature, ongoing studies on human embryonic stem cells (hESCs) by scientists with a record of accomplishment in the field. They were designed for investigators with well-developed expertise in hESC research or in a closely-related field to pursue new directions in hESCs based on their current research.

“These grants provide substantial support to a pool of very distinguished researchers in human embryonic stem cell research,” declared Zach W. Hall, Ph.D., CIRM’s President and Chief Scientific Officer. “These grants are larger than the Leon J. Thal SEED grants approved in February and extend over four years rather than two. Accordingly, our reviewers had higher expectations and more rigorous standards for judging this set of applications.

“The ICOC has approved a very well-balanced portfolio of research proposals, including those aimed at understanding stem cell differentiation and identifying new ways of obtaining hESCs, and many that target specific diseases,” Hall said. “Combined with our training and SEED grants, the CIRM is now funding embryonic stem cell research in more than 100 California laboratories.”

“We focused our initial grants on human embryonic stem cells specifically,” Klein said, “because human embryonic stem cell research receives minimal funding from the federal government, and even those funds are restricted to lines of questionable value. Going forward, we will support a diverse range of stem cell research projects. There are a number of California institutions that have strong programs in adult and other stem cells, for example, that are just beginning to build embryonic stem cell capabilities. Many of these institutions may be prominent names in future grant awards. We need them to be fully engaged in this project, if we’re going to achieve our objectives. Fortunately, we have 10 years and $3 billion to build a strong program encompassing all of California’s research institutions.”

Like the Leon J. Thal SEED grants, the Comprehensive Grants will fund a broad range of projects, including:

* A study of how chemical modification of DNA in hESCs impacts nerve formation and the ability of stem cells to repair brain damage caused by stroke (UCLA)



* Development of new ways of deriving hESCs and investigating the special capabilities of newly-derived human cell lines. (UCSF)



* A proposal to develop neural cellular models of Parkinson’s disease and Lou Gehrig’s disease (ALS) that could be used to screen chemical libraries for novel drugs and to develop preclinical models of human disease (Salk Institute)



* Building tools to better isolate heart and blood cells from differentiated populations of hESCs (Stanford)



* A proposal to optimize the creation of liver cells for transplantation, and be able to monitor their in-vivo fate non-invasively (UC Davis)



* A study of molecular mechanisms regulating hESC survival, focused on a very specific and promising class of growth factors (UC Irvine)



The ICOC approved Comprehensive Research Grants to the following researchers (Note: the dollar amounts shown are the four-year budgets requested by each applicant and are subject to review and revision by CIRM, prior to the issuance of grant awards):



Application #


Principal Investigator


Institution


Title


Amount

RC1-00100-1


Baker, Dr. Julie C


Stanford University


Functional Genomic Analysis of Chemically Defined Human Embryonic Stem Cells


$2,628,635

RC1-00104-1


Bernstein, Dr. Harold S


University of California, San Francisco


Modeling Myocardial Therapy with Human Embryonic Stem Cells


$2,229,140

RC1-00108-1


Crooks, Dr. Gay Miriam


Children's Hospital of Los Angeles


Regulated Expansion of Lympho-hematopoietic Stem and Progenitor Cells from Human Embryonic Stem Cells (hESC)


$2,551,088

RC1-00110-1


Donovan, Professor Peter


University of California, Irvine


Improved hES Cell Growth and Differentiation


$2,509,438

RC1-00111-1


Fan, Dr. Guoping


University of California, Los Angeles


Epigenetic gene regulation during the differentiation of human embryonic stem cells: Impact on neural repair


$2,516,613

RC1-00113-1


Fisher, Dr. Susan J.


University of California, San Francisco


Constructing a fate map of the human embryo


$2,532,388

RC1-00115-1


Gage, Professor Fred H.


The Salk Institute for Biological Studies


Molecular and Cellular Transitions from ES Cells to Mature Functioning Human Neurons


$2,879,210

RC1-00116-1


Goldstein, Professor Lawrence S. B.


University of California, San Diego


USING HUMAN EMBRYONIC STEM CELLS TO UNDERSTAND AND TO DEVELOP NEW THERAPIES FOR ALZHEIMER'S DISEASE


$2,512,664

RC1-00119-1


Heller, Professor Stefan


Stanford University


Generation of inner ear sensory cells from human ES cells toward a cure for deafness


$2,469,373

RC1-00123-1


Lee, Dr. Jang-Won


CHA Regenerative Medicine Institute


Establishment Of Stem Cell Lines From Somatic Cell Nuclear Transfer-Embryos in Humans


$2,556,066

RC1-00124-1


Lee, Dr. Randall James


University of California, San Francisco


Embryonic Stem Cell-Derived Therapies Targeting Cardiac Ischemic Disease


$2,524,617

RC1-00125-1


Lipton, Dr. Stuart A.


Burnham Institute for Medical Research


MEF2C-Directed Neurogenesis From Human Embryonic Stem Cells


$3,035,996

RC1-00131-1


Marsala, Dr. Martin


University of California, San Diego


Spinal ischemic paraplegia: modulation by human embryonic stem cell implant.


$2,445,716

RC1-00132-1


Mercola, Dr. Mark


Burnham Institute for Medical Research


Chemical Genetic Approach to Production of hESC-derived Cardiomyocytes


$3,036,002

RC1-00133-1


Nusse, Dr. Roel


Stanford University


Guiding the developmental program of human embryonic stem cells by isolated Wnt factors


$2,354,820

RC1-00134-1


Palmer, Professor Theo D


Stanford University


Immunology of neural stem cell fate and function


$2,501,125

RC1-00135-1


Pleasure, Dr. Samuel J.


University of California, San Francisco


Human stem cell derived oligodendrocytes for treatment of stroke and MS


$2,566,701

RC1-00137-1


Reijo Pera, Dr. Renee A.


University of California, San Francisco


Human oocyte development for genetic, pharmacological and reprogramming applications


$2,469,104

RC1-00142-1


Srivastava, Dr. Deepak


The J. David Gladstone Institutes


microRNA Regulation of Cardiomyocyte Differentiation from Human Embryonic Stem Cells


$3,164,000

RC1-00144-1


Tarantal, Professor Alice F.


University of California, Davis


Preclinical Model for Labeling, Transplant, and In Vivo Imaging of Differentiated Human Embryonic Stem Cells


$2,257,040

RC1-00148-1


Xu, Yang


University of California, San Diego


Mechanisms to maintain the self-renewal and genetic stability of human embryonic stem cells


$2,570,000

RC1-00149-1


Zack, Dr. Jerome A


University of California, Los Angeles


Human Embryonic Stem Cell Therapeutic Strategies to Target HIV Disease


$2,516,831

RC1-00151-1


Zarins, Dr. Christopher K.


Stanford University


Engineering a Cardiovascular Tissue Graft from Human Embryonic Stem Cells


$2,618,704

RC1-00345-1


Keirstead, Dr. Hans S.


University of California, Irvine


hESC-Derived Motor Neurons For the Treatment of Cervical Spinal Cord Injury


$2,396,932

RC1-00346-1


Kriegstein, Dr. Arnold R.


University of California, San Francisco


Derivation of Inhibitory Nerve Cells from Human Embryonic Stem Cells


$2,507,223

RC1-00347-1


Leavitt, Dr. Andrew D.


University of California, San Francisco


Understanding hESC-based Hematopoiesis for Therapeutic Benefit


$2,566,702

RC1-00353-1


Wallace, Professor Douglas C.


University of California, Irvine


The Dangers of Mitochondrial DNA Heteroplasmy in Stem Cells Created by Therapeutic Cloning


$2,530,000

RC1-00354-1


Weissman, Dr. Irving L


Stanford University


Prospective isolation of hESC-derived hematopoietic and cardiomyocyte stem cells


$2,636,900

RC1-00359-1


Zern, Professor Mark Allen


University of California, Davis


An in vitro and in vivo comparison among three different human hepatic stem cell populations.


$2,504,614





Total $74,587,642



Totals for each institution are listed below:



Institution


Comp Grants


Amount

UC San Francisco


7


$17,395,875

Stanford University


6


$15,209,557

UC San Diego


3


$7,528,380

UC Irvine


3


$7,436,370

Burnham Institute for Medical Research


2


$6,071,998

UCLA


2


$5,033,444

UC Davis


2


$4,761,654

The J. David Gladstone Institutes


1


$3,164,000

Salk Institute for Biological Studies


1


$2,879,210

CHA Regenerative Medicine Institute


1


$2,556,066

Children’s Hospital of Los Angeles


1


$2,551,088

Total


29


$74,587,642





The ICOC also completed its review of the Leon J. Thal SEED Grant applications. Nearly $45 million was approved in February, to 72 scientists at 20 institutions. Today the ICOC approved two additional grants to the following researchers (Note: the dollar amounts shown are the two-year budgets requested by each applicant and are subject to review and revision by CIRM, prior to the issuance of grant awards):



Application #


Principal Investigator


Institution


Title


Amount

RS1-00308-1


Stainier, Dr. Didier Y.R.


University of California, San Francisco


Endodermal differentiation of human ES cells


$635,242

RS1-00247-1


LaFerla, Dr. Frank M.


University of California, Irvine


Development of human ES cell lines as a model system for Alzheimer disease drug discovery


$492,750



Total $1,127,992

The first scientific grants approved under the Stem Cell Research and Cures Act totaled $37.5 million, and were awarded in April 2006, to train 169 pre-doctoral, post-doctoral, and clinical fellows at 16 non-profit and academic research institutions. With today’s decision, the ICOC has now approved more than $158 million for research grants at 23 California institutions:









Institution


Training Grants


SEED Grants


Comp Grants


Grants


Funds (Requested & Awarded)

Stanford University


1


12


6


19


$26,519,988

UC San Francisco


1


9


7


17


$25,796,219

UC San Diego


1


6


3


10


$14,821,287

Burnham Institute

for Medical Research


1


8


2


11


$13,381,881

UC Irvine


1


7


3


11


$13,581,435

UC Los Angeles


1


7


2


10


$12,907,906

UC Davis


1


2


2


5


$8,286,877

The J. Gladstone Institutes


1


3


1


5


$7,920,705

The Salk Institute

for Biological Studies


1


3


1


5


$6,605,126

Children's Hospital of Los Angeles


1


1


1


3


$5,578,107

University of Southern California


1


4





5


$5,405,461

UC Berkeley


1


2





3


$3,446,378

CHA Institute of Regenerative Medicine








1


1


$2,556,066

UC Santa Cruz


1


2





3


$2,132,200

California Institute of Technology


1








1


$2,071,823

The Scripps Research Institute


1


1





2


$1,836,280

UC Santa Barbara


1








1


$1,218,242

UC Riverside





2





2


$1,139,456

Buck Institute for Age Research





1





1


$734,202

Human BioMolecular Research Institute





1





1


$714,654

Ludwig Institute for Cancer Research





1





1


$691,489

UC Merced





1





1


$363,707

City of Hope, National Medical Center





1





1


$357,978

Totals


16


74


29


119


$158,067,467





About CIRM

Governed by the ICOC, CIRM was established in 2004 with the passage of Proposition 71, the California Stem Cell Research and Cures Initiative. The statewide ballot measure, which provided $3 billion in funding for stem cell research at California universities and research institutions, was approved by California voters, and called for the establishment of an entity to make grants and provide loans for stem cell research, research facilities, and other vital research opportunities. For more information, please visit www.cirm.ca.gov.







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Two SEED Grants Approved

The California stem cell agency Friday approved two SEED grants left over from last month's session. They were were numbers 308 and 247, by Didier Stanier from UC San Francisco and from Frank LaFerla of UC Irvine.

CIRM has prepared a press release on the awards that should be posted shortly on its web site, www.cirm.ca.gov.

Correction

In the item below, we incorrectly reported that 24 grants were approved. In fact, the number is 29.

CIRM Hands Out Nearly $75 Million in Stem Cell Grants

The California stem cell agency Thursday night approved $74.6 million in embryonic stem cell research grants that could have an impact on medical problems ranging from Alzheimer's to deafness.

The 29 grants that were approved were contained in the first tier of those recommended by CIRM's review committee. The funding requests were approved by the Oversight Committee in a single block on a single vote.

Robert Klein, chair of the institute, said that the funding, combined with other grants, ranks California at the top of sources for embryonic stem cell research funding in the world. By the middle of this year, the institute expects to have given away something on the order of $200 million or more to beef up ESC research.

CIRM has called a news conference for Friday morning to announce the grants, bolstered by the presence of the mayor of Los Angeles and the state's top legislative leader.

(Editor's note: An earlier version of this item said 24 grants were approved. The correct number is 29.)

Chiropractors, CIRM and Its Legislative Posture

The 120 men and women who sit in the California Legislature generally tend to think they have prime responsibility for writing the laws that govern the state. And they often get edgy when state agencies, even ones that have special constitutional status, seem to be straying from the governmental straight and narrow.

Such was the case recently with the California's chiropractic board, which is enshrined in the State Constitution. Gov. Arnold Schwarzenegger's appointees to the board became carried away in what a deputy attorney general described as a fit of "lawlessness." Now the board faces a serious legislative investigation that could include elimination of its $3 million budget.

While this is something of a minor tempest – although not for chiropractors -- the chiropractic board shares several things in common with California's much heftier, $3 billion stem cell agency. Both are written into the State Constitution. Both were created by initiative. Both have issues involving conflicts of interest. And both function in near obscurity except when they hand out buckets of money – in the case of the stem cell agency – or when a scandal erupts, as in the case of chiropractic board.

Obviously major differences exist between the two boards, including the quality of the appointees. But the case of the chiropractors illustrates how quickly matters can go awry in an insular agency and how quickly the legislature may move to step in. The case will also probably show how quickly the governor can put distance between himself and what The Sacramento Bee called a "laughingstock."

Last Sunday we discussed the sometimes acrimonious relationship between CIRM and the California legislature, particularly in the light of bipartisan legislation by the chair of the Senate Health Committee, Sen. Sheila Kuehl, D-Santa Monica. Her measure would inject the legislature into the difficult and touchy matter of how the stem cell agency decides to share the potentially enormous wealth from cures developed with state-funded research. After a shaky start with lawmakers, CIRM has moved to improve its legislative relations and keep lawmakers well informed.

Our piece, which appeared as an op-ed in The Sacramento Bee, was necessarily limited because of space. But we wanted to share more that we heard from CIRM and two longtime observers of the agency, who also have been critical of its performance from time to time and sometimes even more often. What follows are virtually verbatim comments.

First, from Dale Carlson, chief communications officer for the stem cell agency:

"We have an active government affairs program underway in Sacramento focused on legislators and statewide office holders, as well as their respective staff members. We want to keep them apprised of our efforts and progress, the status of key regulatory and funding initiatives, and the challenges we are confronting in pursuit of our mandate and obligations.

"The objective is to ensure that key decision-makers have current, accurate, and reliable information about CIRM's activities, the field of stem cell research, and related issues. We seem to receive reports of new scientific developments every week, and with more states committing funding to the field each year, it's likely that pace will accelerate. It's a challenge for us to stay abreast of the science, federal policy, and other states' emerging policies, all of which have an effect on our scientific project.

"We're very proud of the work we're doing, the processes we follow to engage the public in the development of policies and regulations that are required by the law, and the willingness we've demonstrated to adopt and apply good ideas from variety of sources. We want to be recognized as a credible source of information on all things stem cell, regardless of whether the question is directly related to CIRM's activities.

"Our legislative affairs program includes one-on-one meetings and group briefings. (Early in February), for example, ICOC Vice Chair Ed Penhoet and several CIRM staff held a session with staff from the Speaker's office and the Senate Health Committee and others, to review our IP policies for non-profits and for-profits. Both have been the subject of great interest and discussion in Sacramento (as well as throughout the state and in Washington, D.C.), with legislators offering many suggestions for how those policies might be crafted and strengthened. Our presentation described the progress we've made to date - emphasizing that the regulatory process is still moving forward and unlikely to be completed for several months - as well as a review of the issues we're struggling to address. "(Later in February), (CIRM President) Zach Hall, Arlene Chiu, and Mary Maxon (Chiu and Maxon are CIRM staff) conducted a broader briefing on the basics of stem cells, the progress we've made in our first two years, including on the IP policies, and the grants approved by the ICOC.

"Kirk Kleinschmidt, our Director of Legislation and Research Policy, has day-to-day responsibility for the effort. In addition to arranging these group sessions, he's regularly in the capital meeting with individual members. Gene Erbin from Nielsen Merksamer is on retainer to support the effort. Per the provisions of Proposition 71, (Stem Cell Chairman) Bob Klein oversees the legislative affairs program in consultation with the Legislative Subcommittee and the ICOC. He's in regular contact with federal and the statewide office holders as well as the legislative
leadership."

Carlson also said that Klein, Penhoet, Kleinschmidt and Patricia Olson, who led development of the CIRM strategic plan, had a 90-minute meeting with Kuehl last Wednesday.

Carlson said it was a "detailed discussion of our IP policies, the drug/therapy development process and the extensive public process we've followed."

"This is the kind of relationship we want with the legislature. Respectful and substantive. We want them to be assured that we're going about our responsiblities thoughtfully and carefully, and that we welcome good ideas and the opportunity to discuss our efforts."

Carlson said the CIRM board will meet in Sacramento April 10 and expects to finish its meeting in time for board members to visit with legislators in the afternoon.

Jesse Reynolds, project director on biotechnology accountability for the Center for Genetics and Society in Oakland, has followed CIRM closely during the last two years as well as the Prop. 71 campaign.

Here is what he had to say in response to our query:

"Prop. 71 is a deeply flawed set of laws, with numerous exemptions to the norms of transparency, oversight and accountability....

"Hopefully, the leadership of the CIRM won't be as hostile to much-needed reform as it was during previous attempts. Then, the state's 'stem cell czar,' Robert Klein took the unprecedented step of hiring a lobbyist with taxpayer funds. What's more, while serving as chair of the CIRM's governing board, he simultaneously headed up a private lobbying organization, which advocates for more funding and less oversight of stem cell research. These actions are not appropriate for the head of a state agency.

"Klein's statements that 'the Legislature is not needed' and that then-Senator Ortiz was 'an ongoing threat' are not only wrong, but highlight his cavalier attitude in his role as a public servant. As the people's elected representatives, the Legislature certainly has a critical role in overseeing a multi-billion dollar program. As a senator, Ortiz did more for stem cell research and Proposition 71 than any other elected official."

John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumers Rights in Santa Monica, Ca., is another longtime follower of CIRM matters. He said,

"Key to any IP policy are provisions that ensure affordable access for all Californians to any cures or treatments resulting from stem cell research they funded. The ICOC originally envisioned meeting that goal by requiring treatments purchased with public funds to be sold at the federal Medicaid price and that there be a plan in place that would provide access to the treatments for uninsured people.

"In drawing up the actual regulatory language to implement those policies, the ICOC has softened those proposals.....

"I think Kuehl's bill would increase payback to the state, but doesn't do enough to ensure affordable access for all Californians. There should be a provision that if there are unreasonable prices the attorney general can intervene. I cite Genentech's Avastin as an example of what cannot be allowed. The drug was developed with $44.6 million in public funds from the National Cancer Institute yet Genentech charges $100,000 a year for it.

"I'd also like to see action on governance and accountability issues. I don't know what Sen. Kuehl's plans are in this regard. Members of the various working groups should be required to file public disclosures of their interests. All applicants and their institutions should be identified, not just recipients. Finally the ICOC is too large. It should be trimmed from the 29 members who now have seats.

"Another thought: ICOC members themselves have expressed concerns about some provisions of Prop 71. It might be useful for both CIRM and the legislature to attempt to identify such areas and agree on making those changes."

CIRM Lending Plan Resurfaces, State Pension Funds Eyed

California stem cell Chairman Robert Klein Tuesday said $3 billion for stem cell research is not enough and touted a loan plan to leverage the state's investment.

Klein proposed lending a portion of CIRM's funds, which, when they were paid back with interest, could either be loaned once more or used as grants. He also suggested that the mammoth California state employee and teachers pension funds could be tapped for additional investments in stem cell companies and research.

Declaring that CIRM's goal is to develop cures, Klein said, "Three billion dollars is not going to get us there."

Some time ago, a CIRM committee briefly addressed the issue of making loans but put off any additional discussion to deal with more pressing matters.

Klein addressed the loan issue in the context of providing financial assistance for clinical trials, which can be very expensive. He said loans allow money to be "recycled" and increased through collection of interest. He suggested that they would be issued in the form of subordinated debentures to make them more palatable to the businesses involved.

Klein appeared at the Burrill & Company stem cell conference on a panel discussion that was entitled "The CIRM Strategic Plan: Corporate Perspectives."

The panel was chaired by David Gollaher, president of the biomedical industry group, the California Healthcare Institute. The group has expressed displeasure with CIRM's efforts concerning intellectual property, declaring that they threaten commercialization of stem cell therapies.

Gollaher did not specifically cite the CIRM rules or related legislation (SB771 by Sen. Sheila Kuehl, D-Santa Monica) but he warned against placing barriers to development of products. Klein said it was important to provide economic incentives. He said that "preferential pricing has to be modulated and balanced against the primary mission" of the agency, which is to develop cures.

Bruce Cohen, president of Cellerant Technologies, said CIRM's royalty rules are "painful but we can live them." He described them as "measurable and capped." But he said rules dealing with pricing make businesses "very, very frightened." He said they could have a "chilling effect" on a decision whether to take CIRM funds. Cohen noted that many medical firms already have plans to provide access to their products by low income persons.