CIRM Able to Fund Research Excluded by Proposed NIH Regulations

The California stem cell agency today said that the proposed NIH regulations for human embryonic stem cell research are "largely consistent" with the state regulations, although CIRM will be able to fund projects that would be barred from federal funds.

The agency issued a news release on the matter this afternoon. It said,

"The conditions required by the NIH are largely consistent with requirements CIRM has developed for derivation performed by our grantees, according to Geoff Lomax, senior officer for medical and ethical standards. 'For our grantees working with lines derived under CIRM standards, these regulations open the door to broader sources of funding, expanding important research in California,' Lomax said.

"Lomax said that under both sets of guidelines, researchers hoping to use a particular stem cell line must prove that the couple who donated the embryo knew that they would not personally benefit from the work, that they would not benefit from possible commercial applications of the cells, and that they could not place restrictions on the type of research performed with the cell line, among other conditions. He added that CIRM may need to make a minor revision to its regulations requiring that couples be specifically informed of all options for disposing of their excess embryos before donating to research.

"Lomax added that there are important avenues of research funded by CIRM that are prohibited under the draft regulations. These include the creation of new stem cell lines, and any work with lines created through nuclear transfer (sometimes called therapeutic cloning) or parthenogenesis, in which the egg is stimulated to begin division without fertilization.

"'CIRM remains a critical source of funding in California for work that is not eligible for funding by the NIH but that has important scientific value,' Lomax said. For example, embryonic stem cell lines created through parthenogenesis are genetically identical to the donor and could be an important source of stem cells for therapies."

CIRM Posts Timely Info on Research Standards Meeting

The research standards working group of the California stem cell agency meets on Dec. 12 to deal with the use of IVF embryos for which donors were paid and the use of somatic cells in state-funded research.

Already posted on the group's agenda is substantial background material along with other staff-prepared material clearly laying out the policy issues involved.

Interested parties have ample time to assess the matters to be decided and make their own decisions on whether to attend the meeting or send comments that can be considered next week. CIRM is to be commended for the early posting of the information.

CIRM Reviews the Business of Human Eggs

One week from today, the California stem cell agency is going to dig into the hot topic of human eggs – how many can scientists can get and their cost.

To its credit, the agency has posted background material on the subject well in advance of the July 25 meeting of its Standards Working Group in Los Angeles. Providing the material early is a refreshing change from CIRM's recent dilatory practices. The agency is to be commended.

The egg meeting comes in the wake of complaints earlier this year by researchers and CIRM President Alan Trounson that human eggs were not to be had in sufficient quantities for research. Kevin Eggan(pictured) of Harvard, a member of the Standards group, said that he and his colleagues had spent $100,000 advertising for human egg donors with little success.

The problem is that California and other states bar compensation for eggs for research. But handsome payments -- $15,000 and even more -- are made by IVF clinics for the same egg donation process. So most women take the cash.

Eggan made his comments last February. The ensuing discussion set in motion a review of CIRM policies dealing with compensation of donors. The issue also came up briefly last month at the meeting of the CIRM board of directors.

Trounson said scientists are having a "terrible time" securing eggs. He declared,

"It's all because there's no partnershipping arrangements or because they're using very few oocyte material. They're now trying to use cattle eggs, other species. They're floundering."

CIRM has prepared a draft briefing paper dealing with the egg issue. The agency has not completed all of its work on the subject, but it is surveying funding institutions, interviewing scientists and others and determining whether specific cell lines are not being used by CIRM grantees.

The briefing paper lists the following policy questions.

"Should CIRM funded researchers be able to use 'outside' hESC lines if they are derived from IVF-embryos created with paid gametes?

"Should CIRM funded researchers be able to utilize hESC lines derived from IVF-embryos created with paid gametes under an 'authorized authority'?

"Should CIRM funded researchers be be able to utilize IVF-embryos created with
paid gametes to derive new lines?"

Also prepared for next week's meeting is a briefing paper on uses of cell lines derived prior to CIRM regulations.

CIRM Directors to Address Business IP and Lab Grants

Directors of the California stem cell agency meet next Wednesday with a $220 million matter foremost in their minds, but other issues, such as intellectual property rules for grants to businesses, also are up for action.

Criteria and procedures for the $220 million lab grant RFA – the largest single grant effort by CIRM – are likely to dominate the discussion. The meeting is expected to be the last stop before grant applications are sought. California stem cell Chairman Robert Klein is talking about approving the first stage of the grants in January(see item below).

Proposed payback requirements for businesses that receive grants from CIRM, which are part of the IP regulations, are up for possible action. The agenda is vague, but if I were a business interested in having a voice on what could be a multimillion dollar matter, I would want to be present for the Wednesday meeting in San Francisco.

The agenda also includes a proposal for pre-approval of certain Japanese stem cell lines in CIRM-funded research and changes aimed at making it easier to do research in California on reprogramming of somatic cells.

One cryptic agenda item lists consideration of an unspecified proposal from the California State University system. No details were available on the agenda at the time of this writing, but we are attempting to find out more.

CIRM Group Gives Nod to Japanese Cell Lines

The California stem cell agency Friday moved to add some Japanese stem cell lines to two already approved foreign lines and to make it easier for California researchers to engage in experiments to reprogram somatic stem cells.

Meeting in San Francisco in a national teleconference session, the Standards Working Group made positive recommendations in both areas that will be taken up Aug. 8 by the agency's Oversight Committee.

The Japanese lines are ones that are derived under the “Japanese Guidelines for Derivation and Utilization of Human Embryonic Stem Cells.” Geoff Lomax, senior CIRM officer for the standards group, said researchers are seeking as many lines as possible. He also said a delegation of Japanese scientists had requested inclusion of the lines. UK and Canadian stem cell lines already enjoy pre-approval.

The group also discussed the question of varying deadlines for using embryos for derivation of stem cells. Prop. 71 sets a deadline of 12 days after cell division. The Japanese deadline is 14, as is the UK, according to testimony. Bernie Lo, chairman of the standards group, noted that it is not currently
actually possible to derive embryonic stem cells beyond 12 days.

After some discussion, Lo asked CIRM staff to research the issues involved so that CIRM can act quickly when derivations can occur after 12 days.

The group additionally recommended that CIRM permit reprogramming experiments on existing somatic stem cells that do not necessarily meet the informed consent requirements intended to be used for new cell lines. Ann James, senior university counsel for Stanford University, said researchers at her school wanted maximum flexibility.

Kevin Eggan of Harvard, a member of the CIRM group, said such cell lines have been in use for perhaps as long as a decade and represented a valuable starting point for research into how to reprogram adult cells into pluripotent ones – the characteristic that makes human embryonic stem cells so valuable. Others noted that it would be all but impossible to replicate today's informed consent requirements for those older lines.

Patricia Olson, scientific program officer at CIRM, said permitting use of the older lines would only allow CIRM-funded researchers to do what others already do outside of California.

Background material from CIRM on these issues can be found here.

Upcoming This Week: Japanese Stem Cell Lines, Lab Grants and Presidential Search

From $220 million in lab grants and Japanese stem cell lines to the latest chapter in the search for a CEO, the California stem cell agency is set for a busy week.

We want to point out the background material prepared for the Standards Working Group meeting on Friday. Posted last week well before the meeting, the paper neatly summarized the history behind the matters being considered, touched on the issues involved and offered up draft language to deal with the problem in two cases. It was a good example of staff work that improves the decision-making process.

The standards group, which regulates CIRM-funded research, will consider whether to include some Japanese stem cell lines as "approved" for study. They would join some lines from Great Britain and Canada as ready to use. That means that research using them does not have to go through a more lengthy review process. Specifically, the Japanese lines being considered are ones derived under the "Japanese Guidelines for Derivation and Utilization of Human Embryonic Stem Cells."

The group is also scheduled to consider a problem in connection with informed consent requirements and research involving somatic cell lines. The agency's regulations created a situation in which "existing somatic cell lines obtained with informed consent may not be available for reprogramming experiments unless consent was obtained in accordance with the exact requirements of section 100100 (of CIRM regulations)."

The staff report said,

"The SWG might consider a more flexible standard for use of somatic cells. Interviews with leading researchers suggest the inability to utilize commonly available commercial somatic cells (non-covered stem cell lines) lines would limit CIRM-funded researchers from attempting to replicate studies."

On Wednesday, CIRM will conduct a session for "interested parties" on the $220 million lab grant effort. Proposed evaluation standards are scheduled to be posted Monday on the CIRM web site. Earlier, the agency posted the criteria and scoring. On July 30, the Facilities Working Group will wrestle with the subject once again, but the ball is rolling faster, so you applicants should pay close attention. Don't be shy about communicating with the agency if you can't be at the meetings.

On Tuesday, the Oversight Committee will convene for the third time in a month for a special, teleconference meeting to consider presidential compensation and candidates. They are legally equipped to come to a decision in their seven-month effort. But our bet is that no new president will be announced.

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.

Magnus: Do We Need More Guidelines?

"Too little, too late." That's what Stanford ethicist David Magnus has to say about the recommendations released last week concerning embryonic stem cell research.

The proposals came from the International Society for Stem Research. But Magnus asked, "Do we really need another set of guidelines."

Writing in the San Jose Mercury News, he said:

"The ISSCR group missed a real opportunity to address many new challenges that stem-cell researchers and oversight committees face -- challenges that have had little attention.

"All of the guidelines to date focus on bench research. But Menlo Park biotech company Geron has already announced that it intends to start clinical trials using differentiated embryonic stem cells for patients with acute spinal cord injury. Yet we have almost no guidance on how oversight committees should evaluate these trials or what should go into informed consent forms. Astonishingly, neither the NAS nor ISSCR has said anything about the right of subjects who may oppose stem-cell research to know that the cells placed in their bodies for research come from embryonic stem cells."

Magnus also said that the "one really novel stand" from the group concerned payment for eggs for research. He continued:

"The ISSCR group says local oversight committees should determine the appropriate policy: no payment, reimbursement of direct expenses, or substantial compensation for time and suffering. The problem with this recommendation is that it seems to fly in the face of virtually every law in place. The NAS guidelines call for a prohibition on payment of egg donors beyond direct expenses. Proposition 71 has a similar ban in place. Many other states and countries have made it unlawful to pay women more than a token amount or to pay anything beyond their direct expenses.

"Many researchers are worried that they will have a difficult time getting access to the eggs they need. But offering standards that cannot be followed by any of the major players in stem-cell research is a recipe for irrelevance."

The recommendations have been praised by John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumer Rights, who said:

"We are pleased the international guidelines stress public benefit and we will continue to insist that California's regulations provide affordable access to any discoveries or cures resulting from research funded by the state program. Too often stem cell advocates have hyped the immediate benefit of stem cell research. I'm delighted to see the call for realism. The Scientific Strategic Plan for the California Institute For Regenerative Medicine already reflects that realistic approach."

Reporter Terri Somers of the San Diego Union-Tribune quoted Larry Goldstein, an ESC researcher at UC San Diego and a member of ISSCR task force, as saying.

“Realizing that stem cell research is an international community, we have to be able to share cells and our scientific methods across borders with some confidence that we have been doing our work to some agreed-upon ethical standards.”