CIRM's Research Standards -- A Look at Their Principles and Reasoning

If you looking for a good overview of the rationale and background for the research standards enacted by the California stem cell agency, check out an article on PLoS Medicine by three men deeply involved in the subject.

The piece is called "Responsible Oversight of Human Stem Cell Research: The California Institute for Regenerative Medicine's Medical and Ethical Standards." It was written by Geoffrey P. Lomax, Zach W. Hall and Bernard Lo.

Hall is the former president of CIRM. Lomax deals with the institute's research standards development. Lo is with UC San Francisco, where he deals with medical ethics. He also serves as co-chair of CIRM's standards working group.

The ESC regulations developed by CIRM broke new ground in some areas and were the most refined in the nation at the time they were promulgated.

The article notes:

"Because other states and jurisdictions may also be developing standards for hESC research, consideration of the principles that guided the CIRM efforts and the innovative measures that it enacted may be useful to others."

One of the excellent attributes of the piece is that it is not hidden behind a private Web site that costs hundreds of dollars to access. It can be found gratis at the www.plosmedicine.org.

Fresh Comments

Lawrence Ebert has posted a comment on the $220 million item. Don Reed has posted a comment on Canadian-California item. Thanks, Don, it is nice to be back in the Old Country.

The $220 Million Lab Giveaway and Its Rules

Scientific laundromats, silos and collaboration benches.-- all were part of the discussion Thursday as the California stem cell institute began developing its criteria for giving away $220 million to build major research facilities.

The meeting was unusually well attended, with the audience easily exceeding the size of those usually at CIRM's Oversight Committee meetings. The actual numbers, however, were less impressive – something slightly over 30.

They were there because they represented universities and others hoping to win multimillion dollar grants to build new science complexes. USC(at least six representatives)UC San Francisco (at least two), Stanford(at least two), Children's Hospital of Oakland(one), UC Berkeley(two), UC Davis (one), UC Irvine (one) all were on hand.

The CIRM Facilities Working Group, which makes recommendations on lab grants, heard some interesting suggestions during the presentations and questions following.

Robert Klein, chairman of CIRM, several times said he expected some applicants to match the grant amount 100 percent, well exceeding a possible nominal match requirement of only about 20 percent. Also surfacing during the discussion was the suggestion that applicants who could line up major contributions – in kind or cash -- from industry might also be more favorably regarded. Other possible industry linkages could be important as well.

Some of the additional questions surfacing directly or indirectly: Is there going to be an effort to spread the grants around the state? How can smaller institutions compete successfully? Will there be more than one round of grant applications?

Irv Weissman, Stanford's eminent stem cell researcher, told the group, "You will be beset by all sorts of political and geographic forces."

"People will try to fool you," he said.

Weissman and others urged an emphasis on excellence. He said the track record of the institutions and their scientists is the best way to assure that.

Jeff Bluestone, director of the UC San Francisco Diabetes Center, also emphasized excellence. He and Weissman additionally spoke of the need to prevent scientists from becoming isolated in "silos" in the proposed labs.

"Successful buildings are ones that have people bumping into each other," Bluestone said.

At one point, CIRM Oversight Committee member Janet Wright used the expression "scientific laundromats" to describe space that can allow for informal research exchanges.

Weissman offered up collaboration benches as one way of bringing in researchers from locations that do not have facilities that match those of major institutions.

Jeff Sheehy, a CIRM Oversight Committee member, said he was interested in providing for opportunities for many institutions.

"Everybody should get a fair shot at attempting to do stem cell research in California," he said.

Thursday's hearing in San Francisco was the first of four. The next will be Monday in Los Angeles, the third June 11 in Sacramento and the fourth in San Diego June 19. You can find more information here and here.

Grant applications are expected to be solicited this August with grants awarded early next year.

Needless to say, it would behoove any institution that expects to seek building grants to attend and participate in these meetings. They offer an opportunity to shape the criteria but also can provide insight into the thinking of some of the players who will be making decisions on who receives the money.

CIRM Legislation Now on Senate Floor

Legislation to ensure a fair return to California from products developed as the result of state-funded stem cell research has moved to the floor of the state Senate, where it faces a major challenge for passage.

The bill, which is also aimed at ensuring affordable access to state-funded stem cell cures, must gain a super, super-majority vote to win approval in the Senate. The requirement for a 70 percent vote was written into the state Constitution in Prop. 71 by stem cell proponents who wanted to make it difficult for elected officials to fiddle with the $3 billion research effort.


The bill, SB771, cleared the Senate Appropriations Committee on Thursday after the Democratic Senate leadership approved its removal from a "suspense" file.

It is not known when the measure by Sen. Sheila Kuehl, D-Santa Monica, and Sen. George Runner, R-Antelope Valley, will come up for a vote in the Senate.

The Canadian-California Stem Cell Treaty

California Gov. Arnold Schwarzenegger did not exactly blow the dome off the Capitol -- newswise -- with his stem cell announcement in Canada yesterday.

Coverage was minimal. Perhaps the most details can be found on the governor's web site. California stem cell Chairman Robert Klein, who traveled to Canada as part of the governor's party, is also featured there with a video blog on stem cell matters.

Some excerpts from the governor's statement:

"(Ontario Premier)Premier McGuinty announced the formation of a new Cancer Stem Cell Consortium that will bring together the best minds and resources in California and Canada to fight cancer through stem cell research.

"This project was initiated by the stem cell and regenerative medicine working group of the Canada-California Strategic Innovation Partnership, a unique collaboration between California and Canada stakeholders from academia, the private sector and government."

"The Ontario Institute of Cancer Research will donate the first $30 million (Canadian) to fund the Consortium, benefiting both Canadian and Californian researchers."

"UC Berkeley's Stem Cell Center and Canada's International Regulome Consortium will coordinate research and take advantage of each institution's expertise."

The CIRM Budget and Burger King

The California stem cell agency plans to nearly double its staff during the next 12 months or so.

That means it will grow from tiny to not-so-tiny. In other words, from 24 workers to 41.

The additions are much needed. Beleaguered might be too strong a term to apply to the staff, but it probably was appropriate on some days during the last two years.

The additions are part of the budget approved earlier this week by CIRM's Governance Committee. The spending plan totals about $8 million for administrative functions, up from about $7.3 million for the current fiscal year, which ends June 30. The full Oversight Committee is expected to approve the proposal next week in Los Angeles.

CIRM is already seeking applications for the following positions: president, associate legal counsel, grants management officer, grants management specialist, grants technical assistant and scientific program and scientific review officers.

The agency will also see a substantial decrease in costs related to the now finally finished litigation, but CIRM will add $200,000 for legal work related to intellectual property issues.

Lest you fear that CIRM is on a path of rampant bureaucratic growth, Prop. 71 capped the number of employees at 50 to administer the $3 billion research effort. We would have to check, but it is probably fewer than it takes to run a Burger King.

CIRM Legislation: A Cash Cow or Bum Steer?

Legislation to ensure that California garners a decent return on its $6 billion investment in embryonic stem cell research has hit a roadblock and faces a critical hearing on Thursday.

The measure is SB771 by Sen. Sheila Kuehl, D-Santa Monica, and Sen. George Runner, R-Antelope Valley. Kuehl is chair of the Senate Health Committee and Runner is the No. 2 GOP leader in the Senate.

The bill has been shunted into a "suspense" file, along with many others, because the chair of the Senate Appropriations Committee, Tom Torlakson, D-Concord, is uncertain whether the measure would generate more revenue than would the regulations of the California stem cell agency itself.

If the measure is not removed from the suspense file, it will be placed on hold for this year and is not likely to be brought up again until January.

Discussions have been underway between Kuehl, Torlakson, Senate President Pro Tem Don Perata, D-Oakland , and Senate Majority Leader Gloria Romero, D- Los Angeles, about the fate of the bill. Kuehl and Runner are contending that it is impossible to make revenue comparisons between the bill and CIRM regulations because the regulations are not in final form. They also argue that arguments by the biotech industry concerning the adverse impact of the bill are highly speculative. Industry is also not fond of CIRM's rules.

Although the Kuehl bill is up for a nominal public vote, without a nod from the Senate leadership, the bill is not likely to be removed from the suspense file.

The staff of the Appropriations Committee has prepared an interesting analysis of SB771 that indicates that the measure would generate $56 million more for the state over a given period than would CIRM's regulations. Here are some excerpts:

"Based on a direct comparison of state revenues generated under SB 771 and under the CIRM regulations, SB 771 would produce more revenue than the CIRM regulations. In a ten year projection of a sample project modeled under three scenarios (a licensed invention, a low success royalty, and a high success royalty) with an $8 billion public investment, SB 771 would have produced $183.5 million compared to $127.7 million under the CIRM proposed regulations.

"The California Institute for Regenerative Medicine believes that the sample comparison above is misleading, that financial market forces, the interests of private research companies, and the unique nature of cellular therapies will produce disincentives which will substantially reduce the projected returns of 771."

The analysis said it reviewed economic studies of potential Prop. 71 returns although it did not cite them by name. It said the studies projected royalties to the state of between $160 million and $1.1 billion.

Earlier this month, an item appeared on the Internet that bears on the biotech industry position that anything that promises to inhibit returns on stem cell products (such as SB771) will discourage research. In an item called "What Price Innovation?," Merrill Goozner, director of the Integrity in Science Project at the Center for Science in the Public Interest, wrote about industry arguments that Democratic national health care reform plans would choke medical research. Goozner said:

"Is there any evidence to suggest that the pace of significant medical breakthroughs can be associated with higher drug industry sales, profits, profit margins or, perhaps most significantly, R&D expenditures? Or, put another way, given the past decade's very high rates of sales growth, profit growth and R&D expenditure growth, how does one explain the steady downward decline (trend line; there is, of course, year-to-year variation) in the number of significant new drugs emerging from industry labs?"

Where's the Money?

Even today headlines talk about the stem cell "gold rush" in California. And it is years after the Prop. 71 campaign financed a study that seemed to promise as much as $1 billion to the state from state-backed stem cell research.

While the headlines may reflect a paucity of imagination on the part of headline writers, the dreams of buckets and buckets of stem cell cash still energize much of the dialogue concerning ESC research.

Jesse Reynolds, writing on the blog Biopolitical Times, recently revisited the subject of stem cell swag. The occasion for commentary was an article in Nature Biotechnology.

Reynolds, who works for the Center for Genetics and Society in Oakland, said what is remarkable about the piece is what's missing. He wrote:

"There’s no reference to the over-the-top -- yet widely-cited -- optimistic scenarios spun in an economic analysis that was widely touted, and funded, by the campaign to establish the (California) state program."

Reynolds noted that Stanford University professor of health research and policy Laurence Baker was a co-author of both the Prop. 71 campaign study and the Nature Biotechnology article, a fact that Reynolds said was not acknowledged in the magazine.

Reynolds said Baker furiously backpedaled from his campaign study. Reynolds quoted the Nature Biotechnology article as saying:

"[A]t this point predicting particular breakthroughs or economic benefits would amount to little more than speculation.... New stem cell therapies will not necessarily reduce [health care] spending; indeed they may drive spending up...Forecasting and even retrospectively assessing the success of Proposition 71's IP provisions will be extremely difficult."

The economic promises of stem cell research are as of much interest today as they were three years ago. Lawmakers are currently struggling to ensure that the state does, in fact, share in any profits. The biotech industry and CIRM are opposed to that legislation (SB771), authored by State Sen. Sheila Kuehl, D-Santa Monica, chair of the Senate Health Committee.

CIRM itself is in the midst of drawing up rules for revenue sharing involving future grants to California businesses. And elsewhere in the country, other states are launching stem cell research efforts, peddling the idea that it can funnel vast economic benefits into the state.

$30 Million California-Canadian Stem Cell Effort

California Gov. Arnold Schwarzenegger is off on a Canadian junket – privately funded – to promote stem cell research and wine, among other things.

According to some reports, he is scheduled to announce, along with Canadian counterparts, a $30 million stem cell research effort involving the Ontario Institute for Cancer Research and a cancer stem cell consortium in Ontario and California.

According to Robert Benzie of the Toronto Star:

"Schwarzenegger will disclose a new project between the University of California at Berkeley and the International Regulome Consortium, led by Michael Rudnicki, scientific director of Canada's Stem Cell Network and director of Ottawa's Sprott Centre for Stem Cell Research."

Beyond that, little was known about the project, although it appears to be an effort worked out between the researchers with the politicians weighing in at announcement time. Schwarzenegger's own Web site did not mention it on its home page this morning, which emphasized the wine aspects of the trip.

The governor's Canadian foray attracted some controversy because it was privately funded with none of the donors disclosed.

Kevin Yamamura wrote in The Sacramento Bee about the private nature of the trip, although he did include a list of some of the top corporate executives accompanying the governor.

Yamamura quoted Bob Stern, president of the Institute for Governmental Studies in Los Angeles, as saying,

"Why can't the state pay for it? It just looks wrong. Basically, you're having special interests pay for the trip. If taxpayers were paying, we'd know it's all California-taxpayer related."

We're Back!

The California Stem Cell Report will begin postings anew later today. We have spent much time in the Sea of Cortez and later on land in Mexico, preparing our salty home (a sailboat) for a bit of a rest during the next few months. It may not be much of a rest for us, however. Our major assignment will be to help care for some grandchildren for a bit. The sweet little things aside, you all can look forward to more exciting California stem cell tales beginning shortly.

Hoisting Anchor

The California Stem Cell Report will be on a hiatus beginning Saturday morning. As many of you know, this effort is produced primarily from a sailboat on the west coast of Mexico. We are putting out to sea and will not have access to the Internet – only clear water, hopefully reasonably calm seas and pleasant temperatures – for the next few weeks. Look for resumption of operations sometime after the middle of May. The break also means that comments submitted to the blog, which are moderated, will not be posted while we are wandering about the briny deep.

More Fallout from CIRM's Facilities Meeting

The Friday the 13 meeting of the CIRM Facilities group generated additional coverage in the last few days. That was the meeting that precipitated the early departure of the president of the California stem cell agency. The chair of the Facilities group also resigned without explanation following the session.

On May 2, CIRM's Oversight Committee will meet to deal with the fallout.

Science magazine described CIRM President Zach Hall as "rattled " by the Facilities session. The account was based on the transcript of the meeting. Our reading of the transcript, plus knowledge of the cast of characters involved, does not support that characterization. Some who were actually present also do not agree with the description. Today, by the way, was Hall's last day at CIRM.

The San Jose Business Journal wrote about how the lack of lab space is delaying the development of cures based on embryonic stem cell research. We have not seen the entire piece, but this is a message that will be delivered with some emphasis next week at the Oversight Committee meeting. You may recall that patient advocates are taking a go-slower tack on funding research labs.

Fresh Link

We have added a link to a site operated by Ben Kaplan called Ben's Stem Cell News: All The Latest Stem Cell Research and Science News. Ben and his brother were featured in the "Twins" TV ad for Prop. 71, which can be seen on YouTube. Kaplan reports they recently shot another stem cell video for Current TV which is expected to be aired soon.

Coverage on the Cha Retraction

The latest doings in the Cha affair were reported today in the Los Angeles Times and The Scientist magazine, following the report on this site yesterday that the article in question was being retracted by the journal that published it.

William Heisel of the Times began his story by saying:

"A U.S. medical journal will retract an article that set off an international plagiarism dispute but will take no action against the lead author, a prominent South Korean scientist whose Los Angeles institute is in line to receive state funds for stem cell research."

Alison McCook of The Scientist had a similar story but with less detail.

Duplicate Publication: Journal Retracts Cha Article

The Fertility and Sterilityjournal has apparently retracted on grounds of "duplicate publication" a paper also involved in allegations of plagiarism by Korean scientist Kwang-Yul Cha.

The matter became of interest in California after the state's stem cell agency approved a $2.6 million research grant for a subsidiary of Cha's Korean organization.

Tony Knight, a spokesman for Cha, sent a copy of the press release announcing the journal's action to the California Stem Cell Report. The release, however, does not yet appear to be on the Fertility and Sterility journal web site. We have queried the journal concerning the information, which did not address the plagiarism allegations.

Here is the statement from Fertility and Sterility as relayed by Knight. A statement from Cha Health Systems follows along with a link to a piece in The Scientist magazine today on the matter.

"For immediate release: April 26, 2007

"The December 2005 issue of /Fertility and Sterility/ included an article entitled “Quantification of Mitochondrial DNA Using Real-time Polymerase Chain Reaction in Patients with Premature Ovarian Failure.” The article was originally published in the /Korean Journal of Obstetrics and Gynecology /(/KJOG/) in 2004, under a different title, with some authors different from those listed in the publication appearing in /Fertility and Sterility/.

"Based on the prior publication of the article, which is contrary to the standards of /Fertility and Sterility/ and medical and scientific publishing, /Fertility and Sterility /has decided to retract the article and will publish that fact in an upcoming issue of /Fertility and Sterility/. This decision was based only on the issue of duplicate publication and does not reflect on the scientific validity of the paper.

"Dr. Sook-Hwan Lee was listed as corresponding author of each version of the article. Dr. Lee has admitted responsibility for the duplicate publications of the article and states that none of the other persons listed as authors had knowledge that the article submitted to /Fertility and Sterility/ had been previously published in KJOG.

"After carefully considering the facts available to it, /Fertility and Sterility/ has determined that Dr. Lee will not be allowed to publish materials in /Fertility and Sterility/ for the period of three years. No action will be taken as to any of the other persons listed as authors of the /Fertility and Sterility/ article, Kwang-Yul Cha, MD, PhD; Hyung-Min Chung, PhD; Kwang-Hyun Baek, PhD; Sung-Won Cho, MS, and Kyu-Bum Kwack, PhD."

The Cha Health Systems statement said:

"The (journal) said its decision to retract the article was based only on the issue of duplicate publication. We were hopeful that the paper would not be retracted, but we are pleased that the board recognized its scientific merit. We have said from the beginning that Kwang-Yul Cha, MD, PhD; Hyung-Min Chung, PhD; Kwang-Hyun Baek, PhD; Sung-Won Cho, MS, and Kyu-Bum Kwack, PhD. knew nothing of the paper’s prior publication. We are gratified that the /F&S/ board reached the same
conclusion."

The Scientist magazine article on the matter did not contain information on the journal action, but said it had not made a decision on how to handle the plagiarism issue.

CIRM Legislation Advances in State Senate

The California State Senate Judiciary Committee today approved legislation aimed at ensuring that the state receives a return on its $3 billion stem cell research investment and that its citizens receive affordable treatments with any state-financed stem cell cures.

The measure, SB771, was sent to the Senate Finance Committee, its last stop before it reaches the Senate floor.

Sen. Sheila Kuehl, D-Santa Monica, told the committee that her bill merely "keeps the promises" of the Prop. 71 campaign. Sen. George Runner, R-Antelope Valley, co-author of the measure, said it ensures that the campaign was not a "bait-and-switch" effort. Runner also said it was "perplexing and disappointing" to hear opponents of the legislation complain that it would stand in the way of development of cures.

The measure was opposed by CIRM and the biotech industry as represented by the California Healthcare Institute. Their arguments were familiar to those who have read these pages and can be seen in much greater detail in items elsewhere on this Web site than time allowed in today's 15-20 minute hearing.

Kuehl said she was willing to work with CIRM but was not satisfied with its position that the legislation is premature. She the use of the "trust us" argument "is not attractive to me." She also noted that industry sounds as if it has a problem keeping the promises embodied in the Prop. 71 campaign.

Representing CIRM at the hearing was Francisco Prieto, a Sacramento physician and a member of CIRM's Oversight Committee. He reiterated CIRM's position that the legislation was premature and said the agency was making progress in meeting the promises of Prop. 71. Runner indicated that "premature" was not necessarily the appropriate term since the agency has been in place for nearly 2 ½ years.

(For more on the legislation, use the search function in the upper left hand corner of this blog or click on the labels below.)

Correction

The item below incorrectly stated that SB771 would go to the Senate floor after clearing the Judiciary Committee. The bill actually goes to the Finance Committee and then to the floor, if approved by the committee.

Kuehl Legislation Up for Hearing This Afternoon

Legislation aimed ensuring a return on California's $3 billion stem cell research effort and affordable access to state-financed cures is scheduled to be heard this afternoon in a state Senate committee hearing that can viewed live on the Internet.

The measure by Sen. Sheila Kuehl, D-Santa Monica, is on the agenda of the Judiciary Committtee, its last stop before it could move to the Senate floor. The session begins at 1 p.m. PDT today. It can be seen on Calchannel.com. We recommend that you check in earlier to be sure your computer is properly configured to see the action.

The Foundation for Consumer and Taxpayers Rights Monday said the legislation is laudatory but falls short in guaranteeing affordable access to stem cell therapies funded by CIRM research. The measure is opposed by CIRM and the biotech industry.

The foundation said in a letter to legislators written by John M. Simpson, its stem cell project director:

"Foremost among the positive aspects, the bill clearly establishes that the Legislature has an appropriate role in oversight of the state’s stem cell institute, the California Institute for Regenerative Medicine. It requires intellectual property regulations that provide for a fair and reasonable financial return to the state on any discoveries made as a result of state financing. It also requires price discounts for drugs, therapies and diagnostics purchased with public money and that organizations receiving licenses provide reasonable access to therapies, drugs and diagnostics for uninsured Californians.

"However, SB 771 contains no provision ensuring that all Californians will gain affordable access to the results of the research they have funded. No one begrudges a company a reasonable profit. What must be prevented is egregious profiteering when public funds have been used to develop a therapy, drug or diagnostic.

"I wish this were only a hypothetical issue; it is not. Genentech’s lifesaving cancer drug Avastin was launched with the benefit of $44.6 million in public funding. Nonetheless, the company originally priced the drug at $100,000 for a year’s supply. Only after months of outrage has Genentec capped Avastin’s price at $55,000 a year.

"SB 771 needs a provision that would prevent this sort of abuse when public funds help produce important drugs and therapies. The Attorney General must have the power to intervene and reduce prices in similar cases."

Fresh Links and More

We have made a couple of modest changes on this Web site to help readers. They include links to background information on the California Stem Cell Report as well as its financial disclosure. Also added is a link to a short item telling how to search the blog more effectively. A link to the Americans for Stem Cell Therapies and Cures is now included, and the link to the Genetics Policy Institute has been fixed. If you have suggestions for additional links, please send them to djensen@californiastemcellreport.com.

The $222 Million Question and CIRM's Direction

The directors of the California stem cell agency will come to grips on May 2 with the abrupt departure of its president and a related acrimonious flap involving its plans to give away – or not give away -- $222 million for research laboratories.

The public will have a unique opportunity to hear and comment on those matters during the first-ever conference call meeting of CIRM's Oversight Committee. Locations are available in many areas of California where persons can listen to the session or make comments. Three in San Francisco, two each in La Jolla and Irvine and and one each in Los Angeles, Sacramento, Carlsbad , Stanford and Duarte. You can find the specific locations on the agenda.

The 29-member committee is scheduled to consider the appointment of an interim CIRM president, probably somebody from within the existing staff. It will also have to find a new chair for the Facilities Working Group.

The May 2 meeting was called after CIRM President Zach Hall moved up his departure date from CIRM two months following a contentious meeting of the Facilities group April 13. The chairman of that group also quit, resigning with no explanation.

Also on the agenda is the go-slow motion from the Facilities group on grants for major labs. The motion was unanimously adopted on April 13 by the Facilities group, which is dominated by patient advocate members of the Oversight Committee. The motion seemed to fly in the face of opposite direction from the full Oversight Committee just three days earlier. The Oversight Committee basically approved the schedule for the grants last year as well the dollars when it approved its strategic plan. However, votes can change.

Nominally nine patient advocates sit on the Oversight Committee but two also have significant ties to institutions that could benefit from lab grants. Fourteen Oversight members, including two patient advocates, have significant ties to institutions that could stand to benefit from lab grants. Here is the list of members.