The California Institute for Regenerative Medicine (CIRM) was formed to provide loans and make grants to enable stem cell research at California-based universities, research institutions and companies, both profit and non-profit. The funds disbursed are the bond proceeds of $3 billion approved by California’s voters in 2004 under Proposition 71. That money can be used to create research facilities and start programs as well as to fund biomedical research and eventually conduct clinical trials of new medicines. All proposals to CIRM are peer-reviewed and money is awarded to develop the most promising diagnostics and therapies that could result in medical treatments and cures that save lives. CIRM also establishes standards and oversight bodies for research and for facilities receiving its funds.

About CIRM (CIRM website)

Embryonic stems cells form days after an egg is fertilized during the blastocyst stage, and they exist as stem cells for only a few days. They then develop into specialized cells, becoming the different tissues of the body. In 1998, two different teams of scientists managed to remove human stems cells from embryos and grow them in a laboratory. Stem cells renew themselves constantly and can be used to develop cures for disease and potentially as replacements for damaged cells.

However, removing stem cells from embryos destroys those embryos, which connects stem cell research to abortions. In 1996, the Dickey Amendment was added to a National Institutes of Health (NIH) appropriations bill that prohibited federal funding from being used in work where human embryos might be endangered or destroyed. The amendment was named for Republican Rep. Jay Dickey of Arkansas, who proposed it, and the amendment was included in subsequent NIH budgets.

One of the first actions of President George W. Bush was to put a hold on funds for stem cell research. Bush then addressed the nation on television in August 2001 to discuss the issue. Citing moral concerns about the destruction of human embryos in the name of research, Bush restricted federal funding of research to a handful of human embryonic stem cell lines, already created.

In response, California real estate consultant and businessman Robert Klein II authored Proposition 71, also called the California Stem Cell Research and Cures Act. Klein, an attorney who had served on boards and proposed policy in the area of affordable housing, was moved to act to fund stem cell research largely because his son was diagnosed with juvenile diabetes in 2001. That and his mother’s battle with Alzheimer’s disease prompted him to fight for research funding in California once federal funds were cut. Proposition 71 proposed that $3 billion in bonds would fund stem cell research in the state for 10 years. Financed by bonds issued by the state, the act provides funding of up to $350 million a year for 10 years.

The act passed with 59% of the vote in 2004, and thus created the California Institute for Regenerative Medicine and its governing board. The act amended California’s constitution, and also included provisions to stop any modification of the act.

Immediately, lawsuits challenging the constitutionality of the act were filed by the Life Legal Defense Foundation representing religious and taxpayer groups. They blocked the sale of bonds and challenged the constitutionality of Proposition 71. While arguments went forward before the court, the institute operated on a $150 million loan from the state and $50 million obtained from private citizens, and awarded grants that made the state the largest funder of embryonic stem cell research in the U.S. Zach Hall, most recently the director of the Zilkha Neurogenetic Institute at USC’s Keck School of Medicine, was appointed president of CIRM. He served until spring of 2007.

Legal roadblocks were finally cleared in May 2007, when the California Supreme Court refused to hear an appeal of lower court rulings. In September, Alan Trounson was named the new president of CIRM, though months would pass before the Australian scientist could move and take up his new duties. September 2007 was also the date set for the sale of $250 million in bonds, the first installment of the $3 billion approved by voters.

With mechanisms to create grants and loans now in place, California became the leader in stem cell research and attracted dozens of scientists from all over the world. By 2007 the state announced that two dozen of the world’s top researchers had moved to California and were working on grants from CIRM.

Controversies plague CIRM over just who is in charge, Trounson, the president of CIRM, or Klein, chair of ICOC, and have led to proposals to reorganize the structure and areas of responsibility for both groups and both top positions. Klein announced in late 2010 that he would step down. Without a new chair, proposals to correct inefficiencies hang in limbo. Critics worry that unless these conflicts are resolved, ineffective management will damage CIRM’s credibility both with voters and with the scientific community.

A Brief History, Current Status Report and Options for Next Steps (CIRM website) (pdf)

History of CIRM (CalPoly)

CIRM makes loans and grants to fund stem cell research by California-based institutions, both profit and non-profit. All funds are given through direct requests for applications, and procedures are outlined on the site’s application page.

The CIRM is governed by a 29-member board called the Independent Citizens Oversight Committee (ICOC), also called the Governing Board. The ICOC is made up of appointed public officials from academia, research institutions, the life sciences biotechnology industry and patient advocacy groups. In addition to 22 appointees named by elected state officials, chancellors of the University of California at San Francisco, Davis, Los Angeles, Irvine, and San Diego each appoint an executive officer from their campus. The chair and vice chair of the ICOC are nominated by California’s top officials: the governor, lieutenant governor, state controller and state treasurer, and then elected by other members.

Although it has a governing body (ICOC), CIRM itself handles the recruitment of scientific and medical talent, the hiring, support, and direction of staff, management, and working groups of both CIRM and ICOC, the development of budgets, the management of performance of all grant recipients, the execution of intellectual property agreements and contracts, and the implementation of policy.

The ICOC manages other aspects of CIRM. The ICOC oversees all operations of CIRM and develops the CIRM’s annual and long-term plans for research, cash flow and bond financing. The ICOC issues public reports on the CIRM, ensures that audits are conducted, and makes the requests for loans and bond issuance. The ICOC makes the final decision on grant awards. It develops research standards and policies about the intellectual property rights of funded research and negotiates for those rights. The ICOC is also the body that can accept additional revenue to supplement grant funding and CIRM operations. ICOC oversees and implements the policies of CIRM and interfaces with the state Legislature.

Three working groups were created with these agencies: The Grants Working Group evaluates research grants and is made up of scientists representing top institutions outside the state and patient advocates on the ICOC. The Standards Working Group recommends medical and ethical standards; its members are all from the ICOC. The Facilities Working Group recommends funding for facilities; again, all its members are from the ICOC. In addition, the ICOC has several subcommittees, dealing with governance, finance, communications, science, evaluations, legislative issues, IP, and biotech loans.

An ongoing source of criticism is the lack of clear delineation of responsibilities between CIRM and ICOC, and between the president and the chair.

Frequently Asked Questions (CIRM website)

Right Medicine for CIRM: Front Page Paean to Stem Cell Research (California Stem Cell Report)

The CIRM’s budget comes entirely from the California Stem Cell Research and Cures Fund, approved by California Voters in 2004. State Operations account for $14.3 million, while nearly $307 million goes to “local assistance.”

According CIRM’s list of funded institutions, by May 2011 almost $1.25 billion had been committed to 55 institutions. The top beneficiary of the CIRM is Stanford University, with 60 funding awards totaling more than $192 million. The five universities represented by an executive officer in ICOC received commitments of 176 awards totaling more than $480 million. Other universities that received grants include the University of Southern California and other campuses of the University of California. Institutions such as the City of Hope National Medical Center, Scripps Research Institute, the Sanford Consortium for Regenerative Medicine and many others have received awards in the tens of millions of dollars.

List of CIRM-Funded Institutions (CIRM website)

Searchable List of All CIRM Grants (CIRM website)

3-Year Budget (pdf)

Ethical Concerns

Since scientists cannot harvest embryonic stem cells without destroying a blastocyst, and since a blastocyst is a human embryo, those expressing opinions about embryonic stem cell research often fall roughly into the same camps as pro- and anti-abortion forces. The blog Catechism on Call explains a position held not only by Catholics, but by many religious people: “If a human person comes directly from an embryo, then an embryo must be the earliest stage of human life, and therefore should not be destroyed for research.”

However, even some conservatives such as Republican Sen. Orrin Hatch support embryonic stem cell research because of the promise it holds to develop treatments for such heartbreaking diseases as Alzheimer’s and Parkinson’s, or for conditions like spinal cord injuries. “Being pro-life is more than caring for the unborn. It’s caring for the living as well,” Sen. Hatch said when interviewed by Charlie Rose. “How can you justify the discarding of 7,000 to 20,000 live in vitro fertilization embryos every year and allow them to die as hospital waste, and not use them for the benefit of mankind?”

The Catholic Stem Cell Position (Catechism on Call)

Unrealistic Expectations

“Vote yes on Prop 71. It could save the life of someone you love.” This and other slogans thrown at voters in 2004 led many to expect immediate and dramatic results from stem cell research.

An editorial titled “California’s Proposition 71 Failure” begins: “Five years after a budget-busting $3 billion was allocated to embryonic stem cell research, there have been no cures, no therapies, and little progress.” The editorial claimed that “backers of Prop 71 are admitting failure.” A former director of the National Institutes of Health is quoted, saying that embryonic stems cells are obsolete. The story then claims they are dangerous as well because “ES cells require the heavy use of immunosuppressive drugs. Their use can lead to a form of tumor called a teratoma.”

A June 2011 opinion in LifeNews.com gloats, “The people of California were promised cures and the citizens of the nearly broke state believed those promises.” The writer, an anti-abortion Catholic and clinical laboratory specialist, finished up, “I hope Californians have learned their lessons and I hope other states learn from their mistakes.”

In spite of these dismal judgments, the CIRM’s web pages and press releases are full of announcements that claim the opposite. In May 2011, for example, CIRM’s guest blogger Roman Reed celebrated a $25 million loan to Geron to fund “a trial testing the use of an embryonic stem cell-driven therapy for spinal cord injury.”

Avoiding both false promises and defeatism, the NIH stem cell institute presents its case for stem cell research, compares the uses of embryonic and adult stem cells, and gives realistic assessments of what benefits could result from stem cell research, and what problems are faced.

“Steering between an over-optimistic view of what is possible and a hyper-pessimistic commitment to inaction can be difficult,” wrote Lawrence S. B. Goldstein in the Sacrament Bee. Goldstein is the director of the stem cell program at the University of California, San Diego, and he described a collection of complicated strains of research and how they could benefit victims of disease and injury. “Is progress using these and many other approaches utilizing stem cells guaranteed to lead to progress for all disease?” Goldstein queried, and answered no. “But it is important to realize that CIRM supports a broad portfolio, and it is exactly this type of broad portfolio that can buffer failures with a steady supply of successes.” He admitted that “none of this will be quick,” but asked readers to consider the cost of inaction in the search for cures to diseases like diabetes.

California's Proposition 71 Failure (Investors.com)

Looking Back at Proposition 71 Stem Cell Funding in California (by Rebecca Taylor, LifeNews.com)

Spinal Cord Injury Stem Cell Trials Get $25 Million Boost from CIRM (by Roman Reed, CIRM website)

Promise Is Worth the Risk of Stem Cell Agency (by Lawrence S.B. Goldstein, Sacramento Bee)

Conflict of Interest at CIRM

Charges of conflict of interest at CIRM are common. The journal Nature described CIRM’s problem in an editorial titled California Against Cronyism: “The board that distributes its funding is stacked with representatives from the universities that benefit most from those disbursements.”

Former CIRM president Zach Hall addressed conflict of interest, acknowledging that, “The largest group on the board consists of leaders of research institutions that are grantees of CIRM.” Hall claimed this problem is managed by members abstaining when grants to their institutions are voted on. In one extreme, when awarding $271 million to build research facilities, only seven of the 29 members could vote, because only seven had no affiliation with the possible awardees.

Hall pointed out that “Critics outside the courtroom have been mostly from the left, focusing on issues of transparency, conflict-of-interest, egg donation, and access for all Californians to stem cell therapies developed by CIRM funding.” Hall blamed a “deep gulf between scientific and political cultures at the state level” for a lack of understanding of many of the rules CIRM follows.

James C. Harrison, outside counsel to CIRM, claimed that “CIRM’s Governing Board has set conflict of interest standards that exceed the requirements of state law.”

The stem cell project director for Consumer Watchdog, John M. Simpson, has been assigned to CIRM since 2005. He wrote in 2010 that “it [CIRM] has been dominated by academic research institutions whose representatives hold the largest number of seats on the board. I believe the trend is troubling enough to ask whether the playing field is level for all applicants. I believe there are grounds for concern.” Simpson followed up with suggestions, including the idea of opening up CIRM meetings and conferences to not just grantees, but to all interested parties.

California Against Cronyism (Nature)

Stem Cell Research in California: The Intersection of Science, Politics, Culture and Law (by Zach Hall, Minnesota Journal of Law, Science, and Technology) (pdf)

Text of CIRM Response on iPierian Grant and Campaign Contribution (California Stem Cell Report)

Troubling Trend: Is CIRM Playing Field Level for Business? (California Stem Cell Report)  

The Little Hoover Commission – California’s independent oversight agency – reported in 2009 that, despite success in biotechnology and expanded, cutting-edge research, “the agency [CIRM] remains vulnerable to perceptions of self-interest.” They also found that Proposition 71’s original language resulted in a governance structure that “locks in inefficiencies” and “inhibits CIRM’s ability to adjust to changing scientific and political landscapes.”

The commission urged California’s governor and Legislature to “improve transparency and accountability” by reducing the number of members in ICOC to 15 and changing ICOC’s name to Governing Board. Other blunt suggestions were to streamline governance of CIRM, and by clarifying the roles and responsibilities of CIRM’s president and ICOC’s chair, enhance financial oversight, improve the process for distributing funds, and require ICOC to plan for CIRM’s future.

There has been no hint of action on reducing the size of ICOC, although it is referred to as the governing board more frequently.

Two years after the Little Hoover report, Michael Hiltzik in the Los Angeles Times wrote that CIRM “hasn’t made much of an advance at solving its chronic management difficulties.” Hiltzik enumerated criticisms, repeating the basic themes of mismanagement, lack of transparency, conflict of interest, all exacerbated by the search for a new chair to replace outgoing Robert Klein. Hiltzik also took shots at the “inflated optimism” of the original Prop 71 campaign. Quoting State Controller John Chiang, the institute “hasn’t produced a game-changer in the public mind-set.”

“The institute’s most glaring inadequacy as a state agency is its lack of integration with the state’s overall research investment,” wrote Hiltzik. “That shortcoming has never been addressed by the board except to give the cold shoulder to critics who raise the issue.”

Will changes be implemented? It seems unlikely that any procedures will change before a new chair of the governing board is installed, but CIRM has released revised organizational charts and proposed changes to internal governance, executive responsibilities, and salaries that are being discussed and voted on.

Stem Cell Research: Strengthening Governance to Further the Voters' Mandate (Little Hoover Commission)

Commission Calls on State to Strengthen Stem Cell Board (Little Hoover Commission) (pdf)

Missed Opportunities at California Stem Cell Research Agency (by Michael Hiltzik, Los Angeles Times)

Internal Governance Policy (CIRM website) (pdf)

Embryonic Stem Cell Research

Embryonic stem cells are extracted directly from an embryo at a very early stage of development, when the embryo is still referred to as a "blastocyst." There are about 100 cells in a blastocyst, many of which are stem cells. They can be kept alive indefinitely and grown in cultures, where the stem cells continue to double in number every two to three days. A replicating set of stem cells from a single blastocyst is called a “stem cell line” because the genetic material all comes from the same fertilized human egg that started it.

Should we be doing research using these cells?

No, Don’t Use the Cells

Those who value human life from the point of conception oppose embryonic stem cell research because the extraction of stem cells destroys the embryo. They believe this to be the taking of a life, or murder. Others argue that use of embryonic stem cells poses a medical risk to the recipient. One study cited found 20% of mice treated with embryonic stem cells died from brain tumors and another study claimed that stem cells stored over time produce the type of chromosomal anomalies that create cancer.

Some people claim that money devoted to embryonic stem cell research would be better spent on other less controversial types of research, such as that on adult stem cells. They point to a dearth of game-changing success stories since California passed Prop. 71 in 2004. A few of the more hyperbolic critics fear that the cells will be used to create and harvest human lives for the sole purpose of experimentation.

“The issue has been misrepresented as a choice between cures and Christianity,” Yuval Levin of the Ethics and Public Policy Center said of embryonic stem cell research. He preferred to frame the ethical question as “not about when a life begins but whether every life is equal.”

Levin went on, “And to the extent that the debate is about whether it is acceptable to destroy a living human being for the purpose of science – even for the purpose of helping other human beings – I think that in that sense, the embryo is our equal. That doesn’t mean that I would think of an embryo in the same way that I would think of a three-year-old child, but I would reject a technique that uses either of them for scientific experimentation.”

Yes, Use Them

The range of medical problems that might be treated with embryonic stem cells is enormous and includes: Parkinson’s disease, Alzheimer’s disease, birth defects, spinal cord injuries, cancer, heart disease, stroke, diabetes, transplants and damaged organs. At the very least, the research process would give new insight into all these afflictions. Research using adult stem cells would be far more limited in its scope and application.

Embryonic research advocates argue that the blastocysts have no human features and new stem cell lines already exist due to the common practice of in vitro fertilization. Many fertilized human cells have already been banked but are not being made available for research, they say. Harris polls conducted in 2005 and 2010 found overwhelming public support for embryonic stem cell research with nearly three-quarters of Americans favoring use of embryonic stem cells left over from in vitro fertilization procedures.

Jonathan Moreno of the Center for American Progress and a professor of Medical Ethics, says this to that: “If a child dies from a disease that might have been preventable if we had been able to research that disease using embryos already slated for destruction or persistent refrigeration – such as embryos used at in vitro fertilization clinics – I don’t see how the death of that child contributes to human dignity.”

The Case Against Embryonic Stem Cell Research (Pew Research Center interview with Yuval Levin)

The Case For Embryonic Stem Cell Research (Pew Research Center interview with Jonathan Moreno)

The Real Promise of Stem Cell Research (by Dr. David A. Prentice, Leadership U)

Derivation of Embryonic Stem-Cell Lines from Human Blastocysts (New England Journal of Medicine)

Embryonic Stem Cell Research – Old Controversy; New Debate (by Rachel Benson Gold, The Guttmacher Report on Public Policy)

Embryonic Stem Cell Research Receives Widespread Support from Americans (Harris Interactive)

Stem Cell Research – Pros and Cons (Experiment-Resources.com)

Alan Trounson, 2007-2014

Zach Hall, 2005-2007