Clinic vs. Basic Research: CIRM Funding Priorities

This item is part of the continuing coverage today of the board meeting of the California stem cell agency based on its audiocast.

The California stem cell agency today set a goal of raising roughly $240 million by privately selling state bonds over the next two years, preserving both its touted efforts to push development of therapies in the clinic and basic biological research.

CIRM Chairman Robert Klein told the board that one of those therapeutic efforts, a $210 million disease team program, is a critical piece in marketing the bonds and is unique to the agency. Without it, he said raising the funds not only will be more difficult but would turn the agency's back on its main mission.

Funding priorities came up today during the CIRM board meeting in Sacramento as a result of the financial plight of the agency, which will run out of cash next fall unless it sells bonds, virtually the only source of funding for the program.

Klein wrote the measure that created CIRM in such a fashion that it puts the agency outside the normal budget allocation processes involving the legislature and the governor.

Directors debated the virtues of funding grants for basic biology versus higher profile enterprises aimed at developing potential therapies at a more advanced stage of research.

Marie Csete(see photo), chief scientific officer for CIRM, told the board that scientists at recent hearings on CIRM's strategic plan were emphatic in stressing the importance of basic research, whose grant round sizes have already been cut.

Director Jeff Sheehy, a communications officer at UC San Francisco and a patient advocate representative, said the disease team project is already a year behind schedule. He said,

"We do not want to hamstring the disease team."

Requests for preliminary applications in that round have already gone out. It is scheduled to be awarded in September or October.

The goal set by the board of directors is just that. Klein will come back in late April with more information on his efforts to sell the bonds. The budget and funding priorities are expected to be reviewed again then.

Potholes in Freeways vs. Therapies in the Clinic

"Where are the cures?" is the headline on the piece in the Nov. 10 issue of Newsweek.

The article by science columnist Sharon Begley virtually cried out for a sidebar on California.

Begley wrote about the "valley of death," translational research and the need for industrial skills that can make the production of stem cell therapies economic.

She quoted Hans Kierstead of UC Irvine, mentioned Geron of Menlo Park, Ca., as well as a proposal to create a "center for cures" at the NIH. Along the way, she noted that scientists involved in basic research are wary of the "center" proposal – a feeling that has surfaced indirectly at the California stem cell agency.

But Begley said:

"The existence of such a center would free scientists to go back to making important discoveries, not figuring out large-scale pipetting, for goodness' sake."

All of what Begley wrote about is on the $3 billion plate at the California stem cell agency. And some of the CIRM actions are coming quite soon. The "valley of death," for example, is scheduled to be dealt with next month through a $500 million lending program. Waiting for action from the new presidential administration is not good enough for CIRM Chairman Robert Klein and company.

As Begley concluded:

"There is lots of talk these days about increasing the nation's spending on infrastructure, such as roads and bridges, to lift the economy out of its doldrums. Me, I'd be willing to put up with potholes in exchange for a new administration spending serious money to take the discoveries taxpayers have paid for and turn them into cures."

Text of Kessler's Conflict-of-Interest Comments

Steven Kessler, a research director with Advanced Cell Technology Inc., of Los Angeles, last month raised a question about a conflict of interest on the part of one unnamed CIRM scientific grant reviewer.

Kessler also addressed the issue of reviewer bias and proposed restrictions on the length of an appeal letter.

Here is the text of his remarks at the August CIRM directors meeting, including comments from CIRM Chairman Robert Klein.

Kessler:

"It's my understanding that for the new cell lines awards, that there were 58 proposals overall, that 12 came from for-profit organizations, none of those were recommended for funding, compared to presumably 18 of 38 from not-for-profit organizations. To me, that's clear evidence of bias.

"I've had – we formally appealed this on June 26th. The appeal -- I was the PI on one of them -- was two and a half pages describing for CIRM what a conflict of interest is from a business perspective, and another seven and a half pages specifically rebutting point by point all the reviewers' criticisms. I don't see how we can do this (in less length). We can certainly condense the letter, but what we did was cite the reviewers' comments and what our proposal actually stated that factually contradicted that. It would be more difficult, I think, for the board to understand what actually took place if we didn't do it in that type of a sequence.

"But just to come back to the conflict of interest issues, I've had discussions with CIRM staff just this week following up, citing CIRM's own conflict of interest policy to them on specific issues. One issue was:...If a grant reviewer has a financial relationship with company 'X,'...that is, he's receiving funding from that organization or he's expecting royalty income from some company by virtue of having licensed technology to that company. And that reviewer is sitting in on reviews from other for-profit organizations, companies 'A,' 'B' or 'C' and doesn't recommend those for funding. To us, from a business perspective, that's a conflict of interest.

"This is a bit different from the situation in academia where people quibble about technicalities on papers.... For-profit organizations...invest millions of dollars building up their patent estate because they won't proceed down the development path, which incurs...tens of millions of dollars in expenses, unless they have a clear patent path. So it is really a serious issue if...somebody, some reviewer with conflicts -- and we cited numerous instances (and) in our view there's no reason to recite those right now – where...a reviewer would have every incentive to help impede the competition for the company that he has a relationship with."

Klein:

"Well, I very much appreciate those comments. We do have an existing separate policy for conflicts. We treat them very seriously. We have a separate policy in place for re-review in the event of conflicts. And the staff does a thoughtful analysis. They have gone through and found a conflict in a particular -- potential -- even if they find a potential for a conflict, they look at potentially re-reviewing it. They're trying to err on the side of equity and justice here."

Kessler:

"I realize that. And I was told that the way CIRM interprets its own conflict of interest policy, the example I gave you was not a conflict of interest. So -- "

Klein:

"Okay. So we'll have the opportunity between now and the next session to look at that as well, but we appreciate your comments. Thank you very much."

A "Certain Skew" Among CIRM Reviewers

Jeff Sheehy is a patient advocate member of the CIRM board of directors and a communications director at UC San Francisco. He has served as a CIRM director since its inception and has taken part in the closed-door review of hundreds of grant applications as a member of the CIRM grant review group.

When a public appeal was made to directors last January by one applicant who received a negative review, Sheehy made an interesting comment on the review process.

Here is part of what he had to say,

"It's been my observation within the context of the working group that clinical work is not reviewed (in) the same way as basic science, that we have a certain skew towards basic science in our review process. I talked to one of the reviewers. He says it's almost the nature of the beast....One of the comments that was made is that...that they're on something, but they're not doing anything particularly innovative. But these incremental states are what happens, according to the reviewer I was talking to, who was the expert on translational research, (and that) is what typically find in a clinical program.

"If we look at the new faculty awards and if were to actually have separated out the basic scientists and the clinical scientists, there's a vast gap in the scores except for one exception. And this is because clinical science is not reviewed as highly within the context of how we do our work as basic science. Basic science is new science by definition. Clinical science is incremental steps. I think it's interesting that everyone seems to kind of just gloss over this novel blood collection technique for umbilical cord. This is the kind of things that are important for moving the science forward. This a little thing, but it actually is a very big thing."

You can find additional comments in the transcript of the meeting.

CIRM-Funded Researcher Firebombed; CIRM Should Beef Up Reward

The scientist at UC Santa Cruz whose home was firebombed earlier this month is a CIRM-funded researcher, holding a $500,000 grant to study differentiation of stem cells into motor neurons.

David Feldheim(center of photo), a molecular biologist, won the grant in 2007, one of the first scientists whose research was supported by California's $3 billion agency.

Feldheim was the target Aug. 2 of animal rights activists, part of a recent upsurge in assaults on researchers. Authorities say the crime is being investigated as an attempted murder. The Los Angeles Times reported today that academics in the UC system are "angered and worried," but vow not to be intimidated.

Last week, UC Santa Cruz faculty members and others rallied to support Feldheim and protest violence against researchers. Feldheim spoke to the crowd, along with the UC Santa Cruz Chancellor and the mayor of Santa Cruz, according to the San Francisco Bay Area Independent Media Center, which published a number of photos and comment on the event. (The Feldheim photo is from that report.)

A $50,000 reward is being offered in connection with the firebombing with funds from the FBI, UC Santa Cruz, private citizens, the City of Santa Cruz, the federal government and the Humane Society, according to San Francisco Chronicle reporter John Cote.

J.M. Brown of the Santa Cruz Sentinel reported that the attack came at 5:45 a.m., burning the front door. Brown wrote:

"Feldheim, his wife and two young children fled from a second-floor fire escape. Feldheim's feet were bruised during the escape.

"Minutes later, outside a campus residence less than a mile away, a fire ripped through a station wagon belonging to a colleague. No one was injured in that incident. A third scientist received a threatening phone message at home about the same time."

Last week, Richard C. Paddock and Maria L. LaGanga of the Los Angeles Times quoted UCSC Chancellor George Blumenthal as calling the attack "domestic terrorism." Their story also carried statistics from the Foundation for Biomedical Research:

"In 2000 there were 10 such episodes against biomedical research facilities alone, and in 2006 that figure had grown to 77, according to the group's website. In addition, the type of attacks has changed in recent years.

"'Prior to that, the vast majority of actions taken were against institutions -- break into the lab, steal the animals, trash the facility,' said foundation President Frankie Trull. 'More recently, however . . . they've become much more personal, attacking the researchers at their homes. California seems to be the focus of this activity right now, but not the only focus.'"

The animal rights terrorism issue is not new to this writer. While at The Sacramento Bee, I was the primary editor on Deborah Blum's 1992 Pulitzer Prize-winning series, "The Monkey Wars," which explored the violence against research involving primates.

What was abundantly clear then and even more now is the need for the public – not just academics – to speak out against this terrorism. The community needs to understand that the firebombers explicitly place animal life above human life. The perpetrators should find no shelter from misguided souls who think this is minor mischief.

The California stem cell agency has not yet spoken out on Feldheim bombing, but it has given preliminary support to state legislation aimed at helping to deal with the problem. A strong statement from CIRM is called for, along with a substantial addition to the reward for apprehension of the perpetrators, something along the lines of about $50,000. CIRM Chairman Robert Klein should also direct his private lobbying group, Americans for Cures, to add another $25,000 or so.

Were Some Scientists' Concerns about CIRM's Claims Worthy of Note?

If the California stem cell agency had its druthers, no one would know that there is a dissenting view about its role in the San Diego research that led to clinical trials on a treatment for a blood disorder.

The $3 billion agency has stoutly defended its claim and bolstered its statement with additional evidence, following questions by the California Stem Cell Report.

However, the agency would have preferred that no complaints were publicly raised and nothing written about them if they were.

We first reported the matter on April 15. We are writing today not to rehash the substance of the complaints, but to share with our readers some of the reasoning behind our decision to report the story and to discuss a few of the nuances of how the media work.

CIRM's position is that our item concerning CIRM's original statement relied on a single, anonymous source and would not have been carried by most newspapers. They are partially correct on that point. We did use one anonymous source – "at least one well-regarded, California stem cell researcher" was the phrasing. We had two, but the other one did not go into the details of the issue. We did not want to characterize both as having identical positions. The item also referred to "concerns among some stem cell scientists." But because of the use of a single, anonymous source, many newspapers would not have carried the story as matter of policy.

Anonymous sources usually have an agenda, sometimes one that is hard to detect. Anonymity protects the source from having to take public responsibility for his or her words. We weighed the possibility of not writing about the concerns of these scientists, but decided to proceed.

The scientists' position was supported by evidence; it was not just one person's opinion. If these two were concerned, undoubtedly many others were as well. There is an axiom in business that for every one complaining customer, nine more exist who are unhappy but who are silent. That axiom seems to apply in this case. Finally, California researchers are loath to publicly criticize CIRM. Who wants to offend the three-billion-pound gorilla and risk losing its financial support?

The question appeared significant as a part of the culture of science. It dealt with the credibility of the agency. CIRM's role was regarded as so important that it merited enthusiastic comment from Gov. Arnold Schwarzenegger -- a move presumably promoted by CIRM. The issue also went to the more general question of hype involving embryonic stem cell research. The agency itself, stem cell research advocates and opponents all have warned repeatedly about dangers of exaggeration and promising too much in this highly charged field.

Since the story has appeared, we have learned of more scientists who agree with the essential points made by our sources.

One said,

"The problem with the original CIRM (statement) is that it referred to the SEED grant, which was funded only weeks before the paper was submitted and dealt with an entirely different disease and... was specified by the RFA to be specifically for human embryonic stem cells which are not at all involved in the UCSD experiments....

"They (CIRM) did overstate it and ... it is embarrassing that the Governor's office picked this up as a first example of CIRM's success. It would have been much better to say that CIRM is proud to be associated with such an outstanding success and to feature something about the trainee."

Another said,

"It does all of us a disservice to pretend that CIRM was responsible for the initiation of a clinical trial when every scientist and biotech manager knows that it is simply untrue."

As mentioned earlier, many newspapers would not have carried the story because of policies regarding the use of anonymous sources. Over decades of experience as a newspaper editor and reporter, we have seen those policies, along with others, paralyze newspapers. They know a story is factually accurate, but because people are afraid to speak up and the subjects of stories stonewall and delay, the stories never run. As a result, the public debate suffers. In the case of the CIRM statement, however, the story would not have reached that level. The subject would not have been pursued by mainstream newspapers because it would have have been deemed too arcane and picayune for the general public. However, the issues raised by our sources are important to our tiny, but deeply involved band of readers, who range from Korea to the United Kingdom.

The California Stem Cell Report is a blog and fundamentally a matter of the opinion of yours truly. Many blogs are nothing more than opinion. Over the years, however, we have taken to reporting stem cell news in a more traditional fashion because of the lack of hard information in the media about CIRM affairs. We have also engaged in analysis and commented negatively and positively about how CIRM is spending $3 billion of public money, virtually free from normal governmental oversight. It is a unique endeavor that has had a far-reaching and positive impact on the national and international stem cell scene.

We think California's unprecedented program is worthy of considerable attention. We will continue to offer a home to those who are willing to make thoughtful comments on its performance – even anonymously.

(We provided an advance copy of this commentary to CIRM and told the agency that we would carry its comments verbatim, if it chooses to offer any. Providing advance copies of articles and offering opportunities for verbatim responses are virtually unheard in the mainstream media.)

Flamm Wins Latest Round Against Korean Stem Cell Researcher

Remember the case of Korean stem cell scientist Kwang Yul Cha versus a California physician?

Cha sued Bruce Flamm, a Kaiser physician and faculty member at UC Irvine, for libel, contending that Flamm was engaged in a personal vendetta. The lawsuit involved published criticism by Flamm of a 2001 article by Cha and two others in the Journal of Reproductive Medicine concerning "distant" prayer and IVF success rates.

Today a Los Angeles superior court judge dismissed Cha's lawsuit. Flamm said in a news release:

"Today's ruling is a victory for science and freedom of speech. Scientists must be allowed to question bizarre claims and correct errors.

"Cha's mysterious study was designed and allegedly conducted by a man who turned out to be a criminal with a 20-year history of fraud. A criminal who steals the identities of dead children to obtain bank loans and passports is not a trustworthy source of research data. Cha could have simply admitted this obvious fact but instead he hired Beverly Hills lawyers to punish me for voicing my opinions."

Cha also surfaced in connection with the California stem cell agency when a nonprofit subsidiary of his organization won a research grant from CIRM. After the grant was approved, the media reported its links to Cha along with news about the controversy surrounding some of Cha's research. Last October, Cha's group withdrew its application for the CIRM grant.

It was not known whether Cha plans to appeal the latest ruling.

San Diego Consortium's Stem Cell Lab Plans and How They Came About

The folks in San Diego call it a "collaboratory" – a $115 million structure to be built under the auspices of four of the world's stem cell research powerhouses.

They are the Scripps, Burnham and Salk institutes and the University of California campus at San Diego – all united under the banner of the San Diego Consortium for Regenerative Medicine.

Reporter Terri Somers of the San Diego Union-Tribune Sunday took a front-page look at the project (see drawing), which is seeking $50 million in construction funding from the California stem cell agency. It is scheduled to make decisions in early May on grant applications from throughout California that would led to $758 million in stem cell lab construction.

Somers story was chockablock with interesting stuff. She wrote:

"It took three men the scientists fondly refer to as 'the town elders' – real estate mogul Malin Burnham, Padres owner John Moores and Qualcomm founder Irwin Jacobs – to help it become a reality.

"'Without their pressure, encouragement and support, (the consortium) wouldn't have happened,' said Fred Gage, a stem cell researcher at Salk."

(Moores was a key financial supporter of CIRM, purchasing $2 million in bond anticipation notes from CIRM when its finances were tied up in litigation.)

Somers also reported,

"An out-of-state philanthropist, whom the consortium declined to identify, has pledged to donate $30 million, with $10 million paid upfront. The remainder would be in $2 million annual increments."

Somers said that Moores gave the consortium $250,000 in seed money and requested the institutes come up with $50,000 each. The 7.5 acres for the building comes from UCSD and is valued at $15 million,

She reported that collaborative efforts sometimes have had difficulty in the past, including one involving UC San Francisco and Stanford. Somers wrote,

"The difficulties arise from every institution having its own culture. Smaller institutes relish their autonomy and operating freedom in contrast to larger, more bureaucratic institutions, such as UCSD.

"Issues ranging from who will be the boss to fear of losing donations, or disputes over who will own scientific discoveries, often kill such partnerships before they start, said Zach Hall, founding president of the California Institute for Regenerative Medicine.

"'It's a testament to the vitality and sense of community that is in San Diego that this has happened,' said Hall, who is now retired. Three years ago, when putting together the strategic plan for the state stem cell institute, Hall listed fostering collaboration as a top goal.

"'For these San Diego institutes to overcome all the obstacles is a real payoff for the long-term vision that San Diego had years ago in setting aside some space for the development of scientific activities,' he said."

CIRM scientific reviewers ranked the project at the top of the 12 lab grant applications. Facilities reviewers ranked it No. 4.

However, that does not matter much to some folks who are not pleased about the project. They say it would mean the end to the Torrey Pines Gliderport, which is in the National Register of Historic Places. A meeting is scheduled for Monday night at which some of the concerns of the glider folks are expected to be aired. In Napa, some 600 miles to the north, on Wednesday night, the state Historical Resources Commission will consider whether to expand the borders of the Gliderport.

Somers story picked up some reader reaction on the Internet, which can be found at the end of her story or here. One reader complained about "greedy scientists fighting over patents." Another decried "welfare for professionals in these lean financial times." One reader suggested the lab be located inland in El Cajon to save money. Responded another reader, "All the Right Wing Christian Coalition fanatics in that town would chase them out. EL Cajon is only known for strip bars, meth dens and a nut case mayor."

(An earlier version of this item described the Monday meeting involving the gliderport as a protest meeting. The meeting is actually part of the EIR process.)

CIRM Says: Not So Trivial

The California stem cell agency is defending its statement last week concerning clinical trials stemming from agency-funded research and denies that it put out a press release on the subject.

The comment came from Don Gibbons, chief communications officer for CIRM, in a comment on the Consumer Watchdog web site. Gibbons' comment was directed at the Consumer Watchdog news release that said CIRM funding for the research was trivial (see item below).

Gibbons said,

"Anyone who truly understands how research labs function would not call the CIRM training grant a trivial contribution."

Gibbons continued,

"Also, it should be noted that CIRM did not write a press release or send anything to reporters."

The document put out by CIRM can be found on the "press room" section of the agency's website under 2008 "press releases."

Gibbons' entire comment can be found on the Consumer Watchdog blog under the comments section following the news release by John M. Simpson, the group's stem cell project director.

CIRM Charged with Political Manipulation

The California stem cell agency is "too eager to claim immediate results" from the hundreds of millions of dollars in research that it is funding, the Consumer Watchdog group said today.

John M. Simpson, stem cell project director for the group, said,

"CIRM is jumping on the bandwagon claiming credit for contributions that were at best rather trivial."

Simpson was commenting on the report below – "CIRM Exaggerates Role..."

He said,

"CIRM is too eager to claim immediate results. Certainly we’ll see great benefit as the result of stem cell research, but this political manipulation and hype does a tremendous disservice to all who believe in the value of this research."

Simpson's news release continued:

"Stem cell agency officials repeatedly say, ‘It’s all about the science. If only that were true. More often than not — as in this case — it’s all about appearances, hype and claiming credit."

CIRM Exaggerates Role in San Diego Clinical Trials Research, Scientist Says

The headline last week from the California stem cell agency read: "First Clinical Trial Begins for a Therapy Enabled By CIRM Funding."

The news was big enough that California Gov. Arnold Schwarzenegger issued a statement on April 7, hailing the research as a world-leading effort. The governor said,

"Stem cell research, funded by the California Institute for Regenerative Medicine (CIRM), led to the discovery of this new treatment."

CIRM Chairman Robert Klein touted "the CIRM model designed to accelerate the quest for cures." The news also received attention in some newspapers, including the San Diego Union-Tribune.

But at least one well-regarded, California stem cell researcher thinks the agency engaged in exaggeration – perhaps even "fraud" – in making the claims about the role of its funding.

The researcher, who asked not to be identified, told the California Stem Cell Report:

"It appears as though the CIRM has wrongly taken credit for supporting work published by one of its funded grantees and/or the funded grantee has wrongly given credit to CIRM for supporting their research. In either case, the CIRM’s press release on the subject is self-serving and misleading, at best. The press and hESC stem cell research supporters have already latched on to this false claim by CIRM and, as a result, are mistakenly touting CIRM’s effectiveness in the field."

CIRM has defended its statement, which said,

"Researchers at the University of California, San Diego, used a (CIRM) SEED grant from the California Institute for Regenerative Medicine to conduct stem-cell research that verified a suspect gene mutation was by itself necessary and sufficient to cause a class of severe blood diseases called myeloproliferative disorders."

The CIRM statement, which is carried under the press release section of its web site, was modified following queries by the California Stem Cell Report. The release now says that a CIRM training grant was also involved. The current version of the news release, however, does not mention that it was altered from the original.

The initial version of the CIRM statement reportedly triggered concerns among some stem cell scientists and led to one contacting the California Stem Cell Report.

The researcher said in an email:

"The press release 'First Clinical Trial Begins for a Therapy Enabled By CIRM Funding' states that 'Researchers at the University of California, San Diego, used a SEED grant from the California Institute for Regenerative Medicine to conduct stem-cell research …'. The quoted UCSD press release describes the work as involving 'human cord blood stem cells … to find whether over-expression of a single gene could drive, or initiate, the disease … that looked like PV' and says that the '…work [was] supported in part by grants from the California Institute for Regenerative Medicine…'. Both items in the UCSD press release are corroborated by inspection of the Cancer Stem article cited.

"However, the SEED grant mentioned - RS1-00228-1: Derivation and Characterization of Cancer Stem Cells from Human ES Cells – has nothing to do with cord blood stem cells or PV. The SEED grant involves hESCs and another disease altogether, CML: 'To provide a robust model system for screening novel anti-CSC therapies, we propose to generate and characterize CSC from hESC (10-18). We will investigate the role of genes that are essential for initiation of CML such as BCR-ABL and additional mutations such as b-catenin implicated in CSC propagation (19-30).'

"Thus, any claim that the SEED grant monies were used to support the published research is either in error, an over-exaggeration, or, worse, fraud.

"CIRM needs to investigate which of these possibilities is the correct one, issue a retraction of its claim, and ensure that erroneous claims are no longer proffered by CIRM or its grantees."

The research in question was conducted at the University of California, San Diego, by a team led by Catriona Jamieson. Her article in Cancer Cell said in the acknowledgments section that:

"This work was supported in part by grants from the California Institute for Regenerative Medicine and the Mizrahi Family Foundation to E.K., C.B., and C.H.M.J., the National Institutes of Health (K23HL04409) to J.G., and an unrestricted gift from Targe-Gen Inc."

When queried, Don Gibbons, chief communications officer for CIRM, said,

"Jamieson has had a post doc funded by a CIRM training grant since July 2006, so our funds helped every stage of this work through his salary. The SEED grant to Jamieson was approved in February (2007) and the Notice of Grant Award went to the institution in July. It is typical for institutions to forward fund after an NGA pending arrival of the first check, which happened in September. The journal asked for additional experiments after the initial submission of the paper, and the Seed grant helped complete those added experiments that resulted in final publication.

"The SEED grant does require that Jamieson use embryonic stem cells at some point during the two year grant cycle, but it also funds many other aspects of the science. Our scientific strategic plan does not call for just funding stem cell work directly; it calls for accelerating the field as a whole."

Gibbons later said that UCSD provided no advance funding for the CIRM grant, which was not signed off by UCSD until Aug. 31, 2007, according to another source. Jamieson's article was first submitted for publication Sept. 19, 2007, according to the source.

We asked Jamieson if she had any comment on the CIRM news release issue. She simply referred us to the statement contained in the acknowledgment section of her Cancer Cell article.

The stem cell researcher who is critical of CIRM said that "...because (the agency) perceives a need to produce results rapidly (it) has, perhaps inadvertently and perhaps not, latched on without checking the facts (although in my mind the facts are quite obvious and need little checking)."

AP Story on WARF Patent Matter

Re the WARF patent fight(see item below), here is a link to The Associated Press Story, which has been now carried on the San Jose Mercury News website.

Stem Cell Patent Fight Enters Another Round

Players in the ongoing saga of stem cells, WARF, California and patents rolled out another chapter today with folks on both sides finding something to make them happy.

WARF apparently fired out the first news release, declaring it was "pleased by the United States Patent and Trademark Office’s decision to uphold the claims of a key stem cell patent."

The opposing side, the Foundation for Taxpayer and Consumer Rights of Santa Monica, Ca., and the Public Patent Foundation, said the decision showed the following gains for researchers.

"The original broad patent was abandoned showing it was underserved and new amended claims have been narrowed.

"The original patent covered all embryonic stem cells no matter how they are derived, but the amended 'non-final' ruling, while permitting the patent, narrowed the claim only to stems cells derived from pre-implantation embryos.

"The newest stem cell research technology — Induced Pluripotent Stem Cells (IPS cells) — would clearly not be covered by the narrowed patent.

" Stem cells derived from fetal tissue could have been claimed under the old patent, but now cannot be."

FTCR and the patent group have been personally supported by CIRM President Alan Trounson in their challenge to the WARF patents.

The Wall Street Journal picked up on the story in its health blog, quoting Ken Taymor(see photo), a longtime follower of California stem cell affairs and executive director of the Center for Law, Business at UC Berkeley.

"It’ll be several years before the patent fight shakes out, according to Taymor, who co-authored a recent article on the subject in the journal Cell Stem Cell. 'In the mean time, there is all this other patenting activity that’s going on — patenting activity that’s not being challenged,' he said.

'Those are essential steps for commercialization.'

"What’s more, Geron and WARF hold a lot of the newer stem cell patents. 'So the more interesting question,' Taymor said, 'is what patents do they hold and what’s the scope of the claims that they have downstream in commercialization?' Taymor and his colleagues are looking into that now, and plan to publish their findings."

The story received a fair amount of attention in Wisconsin. At the time of this writing, only one newspaper in California, which is the leading biotech state in the nation, had carried a story. That publication is the San Jose Business Journal, and it wrote based on a Geron press release.

Here is a link to the story in The Scientist.

Fresh Comment: CIRM's Mystery Meeting Remains a Mystery

Marcy Darnovsky of the Center for Genetics and Society makes an important comment on the "mystery" item we posted. She is absolutely right. Those documents from the California stem cell agency should have been posted days ago if CIRM wanted serious public comment. The daylong meeting on Thursday involves complex issues dealing with the ethics and practice of stem cell research. The session could have major implications for the conduct of CIRM-financed stem cell research, but there is no way to know.

CIRM has repeatedly pledged to adhere to the highest standards of openness. Earlier today, we discussed a relatively minor item that belies that pledge. The failure to provide adequate information on the Thursday session, assuming its subject is of some consequence, is a more significant issue. CIRM can and should do better. You can see Darnovksy's comment by clicking on the word "comment" at the end of the item.

Margolis: Beware the Embryonic Cheerleaders

The Stem Cell Blog run by Stanford's Chris Scott carried an interested commentary the other day from Don Margolis, founder of the adult stem cell company, VesCell, who tackles some of the issues related to reprogramming of adult stem cells.

Among other things, Margolis invokes cancer, criticizes "embryonic cheerleaders" (presumably not unborn pom-pom girls) and attacks "censorship" of those who differ with the heralds of hESC.

Margolis also hails the "refreshing" honesty of such folks as Jamie Thomson, George Daley, Doug Melton and Shinya Yamanaka. You can find the piece here.

Tackling Stem Cell Collaboration

Last week, the Mission Bay conference center at UC San Francisco was the scene of a meeting to discuss issues related to stem cell research. We asked one of those involved in organizing the event, Krishanu Saha, to give us a summary of the session. Here is Saha's report.

"In a successful workshop on Feb. 6 organized by the Berkeley Stem Cell Center and the Berkeley Science, Technology and Society Center, scientists, lawyers, ethicists, academic leaders, and patient advocates across California and the US gathered in San Francisco to discuss collaboration in stem cell research (see the "research roadblocks" item on Feb. 2).

"The morning consisted of three panels that described the problems in three interacting domains - the technical, proprietary, & ethical - of California's stem cell research climate. The need for sharing data on stem cell lines themselves was raised by a panel of practicing scientists, and later echoed by panels of intellectual property experts and ethicists.

"Intellectual property in stem cell tools was debated by both members of academia and industry, especially in regard to CIRM's policy. Legal experts and ethicists detailed the challenges of practicing within a patchwork of regulations across states and with tissue/cell donors.

Patient advocates and industrial leaders stressed their involvement in developing better healthcare during lunch, and in the afternoon, discussion shifted to how institutions could collaborate to deal with the problems laid out earlier. Both within stem cell research and other life sciences, several models of collaboration across states, academic institutions, and hospitals were discussed in an open forum.

"Participants agreed that there was a clear need for collaboration among stem cell research institutions and that California institutions will likely be intensely involved. Creating a database among institutions was seen as a potentially feasible first step, however further conversations will be necessary to determine the membership, costs, incentives, and types of data to include.

More information, including an important policy paper regarding this issue and a summary of the workshop, can be found at http://stsc.berkeley.edu/Events/2008StemCellResearchFeb6.htm.

Exploring Research Roadblocks and Cooperation

Intellectual property bottlenecks, data withholding and regulatory complexity involving embryonic stem cell research – all are part of a daylong meeting next Wednesday at the Mission Bay Conference Center of UC San Francisco.

Speakers include Bob Klein, chairman of the California stem cell agency, and its new president, Alan Trounson. Others include Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Institute; Jonathan Auerbach(see photo), president of GlobalStem in Maryland, and Michael West, CEO of Biotime in California, plus a host of academics.

The session is aimed at exploring a collaboration among various institutions to improve research sharing and cooperation.

Here is an an excerpt from a paper prepared in advance of the meeting. The authors are Krishanu Saha, Gregory Graff and David Winickoff, all of UC Berkeley.

"The technical, proprietary, and regulatory conditions currently giving shape to stem cell R&D are far from ideal: closed information, congested entitlements, and regulatory uncertainty present formidable challenges for the conduct of research and its translation into practical applications. Such an environment is likely to slow the pace of innovation, skew the distribution of health benefits towards the wealthy, and force ethical decision-making that lacks public accountability.

"Here we propose an institutional mechanism to coordinate the conduct and governance of human stem cell R&D: a collaboration among academic institutions to collect and make available information detailing the technical, proprietary, and ethical characteristics of cell lines and research tools developed at participating institutions. Centralization would help promote more efficient transfer and use of available and ethically preferential technologies. The coalition could also leverage the collected information to assemble and disseminate complex enabling research tools under common material transfer agreements or patent pools in those cases where multiple patents are necessary but are fractionated across multiple owners."

The session, which is sponsored by the UC Berkeley Stem Cell Center and the Science, Technology and Society Center, also at UC Berkeley, appears to be open to the public with no admission charge.

SC3: The New California Stem Cell Collaboration

Six California research institutions, ranging from the University of Southern California to the University of California at Santa Barbara, today announced a "collaboration" aimed at enhancing their stem cell research efforts.

Martin Pera(see photo), director of the USC Center for Stem Cell and Regenerative Medicine, said,

"Tackling these complex problems requires scientists with diverse expertise. We are delighted to have an opportunity to work with such an outstanding collection of scientists to really accelerate the pace of discovery and translational research in regenerative medicine."

In addition to USC and UC Santa Barbara, the other institutions are Childrens Hospital Los Angeles, City of Hope, the California Institute of Technology and the House Ear Institute.

The coalition is officially known as SC3 – the Southern California Stem Cell Scientific Collaboration.

SC3's news release said,

"The new agreement is a major step forward in supporting potential significant stem cell findings by allowing members to share training programs, scientific core facilities and expertise while teaming up on a wide range of research programs."

Dennis Clegg, director of the stem program at UC Santa Barbara, said, "The SC3 collaboration is already engendering new ideas for collaborative projects between scientists at the participating institutions."

Pera said SC3 is not applying for any of the $227 million in CIRM lab construction grants, which are being reviewed privately today in San Francisco, although USC is. Pera said via email,

"We have dedicated one floor in our proposed facility (Edythe and Eli Broad Center for Regenerative Medicine and Stem Cell Research) to supporting the work of SC3-through training, access to core laboratories with specialized equipment and expertise, and through providing space for collaborative and pilot projects. "

Southern California already has another type of collective effort underway regarding stem cell research – the San Diego consortium involving UC San Diego, Scripps, Burnham and Salk. However, it appears to be more formally structured and is believed to be seeking a large lab construction grant from CIRM.

The stem cell agency has declined to identify any of the institutions seeking grants.

Judge Dismisses Cha Libel Suit Against Flamm

The California physician who criticized Korean stem cell scientist Kwang Yul Cha has won a round in Cha's libel suit suit against him.

Earlier this month, a Los Angeles judge threw out the suit against Bruce Flamm of Riverside, Ca., but Cha has about 60 days to file an appeal, which a spokesman says he is considering.

Cha surfaced in connection with the California stem cell agency when a nonprofit subsidiary of his organization won a research grant from CIRM. After the grant was approved, the media reported its links to Cha along with news about the controversy surrounding some of Cha's research. In October, Cha's group withdrew its application for the CIRM grant.

In the case of Flamm, he published a critical opinion piece concerning Cha's 2001 study that linked prayer to in vitro fertilization success. Cha says Flamm is engaged in a personal vendetta.

Regarding the judge's action, Flamm told The Scientist on Nov. 20:

"This is a great victory for science, peer review and academic freedom."

Burnham's John Reed, Influence and a CIRM Grant Denial

In an apparent violation of a state conflict of interest policy, an influential director of the California stem cell agency earlier this year attempted to overturn a decision by the agency's staff that ultimately resulted in the loss of a $638,000 grant to his research institution.

John Reed, president of the Burnham Institute of La Jolla, Ca., on Aug. 2 wrote a 6 ½ page letter to the agency staff, warning that denial of the grant would set a "dangerous precedent" that would impair the mission of the California Institute for Regenerative Medicine (CIRM). The letter came about as the result of a suggestion by chairman of the institute, Robert Klein.

The California Stem Cell Report (CSCR) obtained a copy of the letter from Reed (see photo) from CIRM after filing a request under the state's public records act for documents relating to the Burnham grant.

In response to questions from CSCR, Richard Murphy, interim president of CIRM, said,

"Dr. Reed called the chairman to ask how to deal with what Burnham saw as technical mistakes in CIRM’s interpretation of the application. The chairman, not knowing enough about the technical details or whether mistakes had been made, suggested that Dr. Reed write a letter to the science team, which was knowledgeable about the issues."

Murphy also said,

"After CIRM received the letter, Dr. Reed was informed that he must refrain from participating in any way in CIRM's consideration of the Burnham grant."

John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumer Rights of Santa Monica, Ca., called for Reed's resignation, declaring that he would file a formal complaint with the state Fair Political Practices Commission, which deals with conflict-of-interest violations.

Simpson, a longtime observer and participant in CIRM proceedings,said, "The law is clear....John Reed flouted the law." He continued, "When you hand out millions of dollars in public money, you have to play by the rules."

Asked whether CIRM contemplated any action regarding Reed, Murphy replied, "Dr. Reed now fully understands the conflict rules. CIRM does not intend to take any further action regarding this matter."

Klein did not respond to an email asking about his role in the Reed letter. Reed also did not respond to questions emailed to him.

Reed presides over a nonprofit research institution that has received $17 million in CIRM grants and that has an annual budget of $87 million. According to Burnham's web site, it has 750 employees and ranks 5th in the nation in NIH funding among private research institutions.

CIRM's policy on conflict of interest states:

"Members of the ICOC shall not make, participate in making, or in any way attempt to use their official position to influence a decision regarding a grant, loan, or contract with their employer.

"Members of the ICOC shall not make, participate in making or in any way attempt to use their official position to influence a decision regarding a grant, loan, or contract that financially benefits the member or the entity he or she represents."

The application for the grant in question came from David Smotrich, an adjunct professor at Burnham and founder of the La Jolla IVF clinic. The grant was highly rated by scientific reviewers, who examined it behind closed doors and made the initial decision to fund it. Their findings then went to the Oversight Committee for final action last February during a public meeting. The application was considered at that time under the board's normal procedures. The names of the applicant and institution were withheld from the public and the Oversight Committee. Reed was barred from voting and taking part in the discussion, but that fact was not known to the public at the time.

Following Oversight Committee approval, the Smotrich application and all other approved grants were scrutinized administratively to assure that they complied with terms for the grants. CIRM staffers did not question the science or the credentials of the researcher. But they indicated as early as Feb. 24, according to CIRM documents, that there were problems with the eligibility of Smotrich. The issues involved whether he was a fulltime faculty member at Burnham, was located on the Burnham site and whether he had his own dedicated lab at Burnham.

The exchange between CIRM and Burnham about Smotrich went on for seven months. The letter from Reed came just as CIRM staff was planning to announce the grant denial at the Oversight Committee meeting early in August.

He said in his "appeal" letter to Arlene Chiu, then the top scientist at CIRM, that Smotrich "rightfully deserves" the grant. He devoted the bulk of his letter to Smotrich's credentials and his research, which included an "embryo rescue program" that would salvage leftover embryos from IVF that would otherwise be discarded.

Reed wrote:

"I also wish to emphasize the potentially damaging consequences that a decision not to recognize Dr. Smotrich's legitimacy as a faculty member may have on clinician investigations, as it will surely discourage clinical researchers from participating in the CIRM mission to advance stem cell therapies. Finally, the particular grant recommended for funding is of great strategic importance to the entire CIRM effort, and therefore we urge CIRM staff to take this into consideration."

Referring to the "embryo rescue program," Reed said,

"This is a unique resource not found anywhere else in the entire state and the only source currently available in California for deriving new hESC lines with the goal to share these freely with the entire CIRM research community to advance the fundamental goals of CIRM. Thus, to abandon the grant on perceived technical grounds flies in the face of the mission of CIRM."

Reed added that denial of the grant "sets a dangerous precedent that adversely affects all clinician-scientists, most of whom will have a significant component of their time devoted to clinical activity and whom will often by supported by non-academic sources."

On Aug. 27, Tamar Pachter, CIRM general counsel, wrote Burnham concerning Reed's Aug. 2 letter. She said his request to appeal the staff decision was rejected because no right of appeal existed for administrative findings. She said the decision did not involve the merits of the research or Smotrich's credentials.

She wrote,

"To be fair to all the applicants (as well as potential applicants who self-selected out of the applications process because they could not meet the eligibility requirements of the RFA), and to carry out its duties as a state agency with integrity, CIRM must consistently enforce eligibility requirements."

Burnham was offered an opportunity to withdraw the application but refused to do so. The decision not to fund the grant was announced late in the day in the waning minutes of the October meeting of the Oversight Committee, a move controlled by Klein in his role as chairman.

The CIRM news release the next day on the meeting did not identify Burnham as losing the grant, a decision made by Murphy, who overruled a recommendation by then chief communications officer Dale Carlson. (Prior to his appointment at CIRM, Murphy was president of the Salk Institute, another medical research organization in La Jolla.)

Carlson had submitted the draft release to Murphy for approval. Its next to last sentence said that the grant to Burnham had been denied. In an email exchange on the evening of Oct. 3 (the day of the Oversight meeting), Murphy said he did not want to mention the Burnham grant.

Carlson then emailed Murphy that the Burnham case and another grant that was withdrawn demonstrated the rigor of staff review and showed that the agency was a good steward of public funds. He wrote:

"Putting out a release in the morning that fails to note these items in light of the press coverage they'll be receiving, would seem like we're being protective and/or inexplicably secretive. Better to include the news at the bottom of the release. It shows we think the items that appear first are more important, but these are at least worth noting."

Murphy then replied to Carlson,

"From CIRM's point of view, you're right. It makes us look meticulous, as we are. But I hate to build our reputation for quality on the carcass of another institution, which no doubt will be embarrassed by the coverage. John Reed will be under fire from his board and donors for allowing this to happen, and we don't want to pile on. Let Burnham handle it anyway they want, but I don't think we suffer by remaining silent. If it hits the fan, I'll take the rap by saying truthfully that it was a technical decision, the science was great, but rules are rules. We did what we had to, and we look forward to their resubmission.

"Thanks for caring so much, but there's a balance on this one, and I think we serve the community kland CIRM best by minimizing the issue and remaining silent."

(Below is the full text of Murphy's response to questions from the California Stem Cell Report.)

(Editor's note: An earlier version of this said that news release following the Oct. 3 Oversight Committee did not contain any mention of the Burnham grant. The news release said a grant had been denied but did not identify Burnham.)