Prop. 14 News Coverage: Los Angeles Times and Politico Take a Crack at the Stem Cell Measure

A $5.5 billion ballot measure to save the California stem cell agency from financial extinction popped up in coverage this week in the Los Angeles Times and Politico, a national political and government news service. 

Both pieces raised questions about the agency and its history, not to mention whether it fits with California's current government priorities.

The proposal is Proposition 14. It would provide the billions to the agency,  expanding its scope significantly into such areas as mental health and therapy delivery that are not necessarily related to stem cells. 

In his piece, George Skelton, a longtime political columnist for the Times, the largest circulation newspaper in the state, noted that the agency was funded in 2004 with $3 billion, which is now running out. Skelton wrote, 

"That’s a ton of money for a little-noticed agency that provides a questionable state service. But many of the research projects have been very worthwhile." 

In the article, the Proposition 14 campaign, headed by Palo Alto developer Robert Klein, also continued its pattern of making exaggerated or misleading claims.  

"If we don’t continue the state funding, lots of facilities would have to close their doors,” says Kendall Klingler, the Proposition 14 spokeswoman....

"'We have more than 90 stem cell trials underway,' she says.

"The agency does have a record of some success: funding research that has led to treatments approved by the Food and Drug Administration (FDA) for blood and bone marrow cancers, for example."

Regarding the number of clinical trials funded by the research program, the agency itself only claims 64. The additional 30 or so trials are not funded by the California Institute for Regenerative Medicine (CIRM), as the agency is officially known. They utilize a piece of CIRM-financed research, however tiny, someplace along the way. And not necessarily a significant piece. 

The FDA treatments mentioned are not stem cell treatments, which is what was promised by the 2004 campaign. The agency has not funded any research that has resulted in a stem cell therapy that is available to the general public. 

And it is simply not accurate to say that "lots" of stem cell facilities partially financed with CIRM cash will be closing. All of them are occupied and fully in use. The recipients of the facilities grants, such as Stanford and UC San Francisco, are exceedingly unlikely to close the buildings.

Skelton concluded that CIRM has "failed to live up to its original hype." He said, 

"It was aloof to Sacramento, and not subject to oversight by the Legislature and governor. There’s been a lack of transparency.

"There was also an odor of interest conflicts among agency board members who seemed to steer grants toward their own institutions, even though they recused themselves from voting."

(In the interest of full disclosure, I worked for Skelton in the Capitol bureau of United Press International in the 1970s when he was bureau chief there.)

Over at Politico, Victoria Colliver wrote,  

"It's not clear that the Yes on 14 campaign's $15 million, even with a campaign that features actor Seth Rogen as “Stemmy the Stem Cell," will get the job done.

"'We’re running against Covid-19. That’s our real opposition,” said Robert Klein, the wealthy real estate investor and attorney who authored both measures and is the main funder of Prop. 14, along with Dagmar Dolby, the widow of inventor and sound engineer Ray Dolby.

"The differences between 2004 and 2020 are stark.

"Back then, Klein and other proponents had a ready-made argument by pointing to President W. Bush's prohibition on federal funding for embryonic stem-cell research, a stance supported by the religious right. In the nation's biotech capital — with an electorate dominated by Democrats and independent voters that support abortion rights — stem-cell backers made the case that California needed to step in to keep research alive.

"Many of the promises made 16 years ago, including its projections in royalties and state revenues from new treatments, have not borne out. Funding from the agency has supported more than 60 clinical trials, but CIRM has yet to fund a single stem-cell therapy approved by the U.S. Food and Drug Administration for widespread use."

Stem Cell Scientist Jeanne Loring on hESC Research, Proposition 14 and California Stem Cell Agency

(Editor's Note: The following commentary concerning the California Institute for Regenerative Medicine (CIRM) and Proposition 14 was submitted to the California Stem Cell Report by Jeanne Loring, professor emeritus from the Scripps Research Institute and co-founder of Aspen Neuroscience, Inc., of San Diego.)

By Jeanne Loring

"Long ago, when Bob (Klein) and Jeff (Sheehy) were both CIRM’s oversight board members, their arguments were legend. I was at the meetings for most of them.

"After listening to the broadcast (KQED’s Forum), I want to make 3 points:

"I want to once more correct the idea that George Bush banned embryonic stem cell research; he did not, and I was disappointed that KQED perpetuated that misconception.

"In 2004 when Prop. 71 was on the ballot, I was already receiving funding from the NIH for human embryonic stem cell research. Bush’s decision was NOT to ban hESC research, but was in fact the opposite. He decreed that hESC research could receive NIH funding for the first time. In effect, he REVERSED A BAN. On the 9th of August 2001, a group of us who had already made hESC lines with private funding became eligible, for the first time, to receive NIH funding. Article: Stem cell research gets federal OK, Aug. 9, 2001.

"In 2004 when voters were approving Proposition 71, there were NIH grants funded for Jamie Thomson in Wisconsin, for Bresagen in Georgia, for several groups in other countries, and for Roger Pederson (UCSF) and me in California. Here’s an announcement from UCSF on September 17, 2002: UCSF begins distributing the first of its two embryonic stem cell lines.

"I supported Prop 71 not because it was necessary, but because it would make California an embryonic stem cell research juggernaut. I believed in the potential of embryonic stem cells and CIRM gave me the opportunity to prove it.

"Bob Klein and I used to talk often, and I admire him for his persistence in getting CIRM established. But as time passed, he seemed to tire of my opinions. Last year I published an opinion piece in Nature that pointed out the unanticipated parallel growth of legitimate stem cell research and charlatan “stem cell” clinics: World View Nature. I immediately received this message from Americans for Cures (Bob Klein’s organization).

'Dear Jeanne,

'On behalf of the organization, I must let you know the following. 

'Unfortunately, Americans for Cures must remove you from its Scientific Advisory Board, effective immediately. Your views in the recent article in Nature are not consistent with the views of Americans for Cures as to CIRM and the importance of CIRM’s accomplishments.'

""I have mixed feelings about Prop. 14. I have benefited greatly from CIRM funding, and after many years of CIRM funding, I was able to attract private venture funding to launch a company developing a cell replacement therapy for Parkinson’s disease.

"'But I agree with Jeff Sheehy that the current measure does not fix the flaws in Prop 71. Having watched the process of approving grants by the oversight board (ICOC) for 13 years, I came to the conclusion that because the Board was made up largely of members representing institutions that were competing for grants, bias was unavoidable, and the large size of the Board, 29 members, was a detriment. The current proposition, Prop. 14, makes the situation worse by increasing the number of board members to 35 and not fixing the conflicts.

"There is a moment at which one’s trust in an organization is dashed. For me this it was this event: the president of CIRM was hosted by a professor at Stanford for at least 2 luxurious fishing trips in Montana and Alaska. This president then argued strongly in favor of large grants to Stanford, and also grants to a company that that same Stanford professor had founded. Finally, when the president stepped down from CIRM he waited less than a week before taking a paid position on the board of the company that he supported for CIRM funding. It was then that the full impact of the intrinsic bias became real to me."

(Editor's note: The reference to the president of CIRM is to its former president Alan Trounson. The reference to the Stanford University professor is to Irv Weissman.)

Proposition 14 Campaign Coverage: George Bush, 'Blatant Giveaway' and $5.5 Billion More

Northern California's respected KQED news site has aired an overview of Proposition 14, the far-reaching, $5.5 billion measure to continue funding of stem cell research by the state of California.

The piece by Danielle Venton covers a bit of the history of the state stem cell agency, the "debt" it owes to former President George Bush and the progress of the agency, known formally as the California Institute for Regenerative Medicine (CIRM). Venton wrote,

"The pace of innovation has been slower than many hoped. As it turned out, grand discoveries were not around the corner, and to date there is no widespread stem cell treatment approved for the public. To date, CIRM has funded more than 64 trials directly and aided in 31 more. Not all have or will result in treatments.

"But despite the lack of a marquee cure like one for Alzheimer’s or Parkinson’s, the agency has seen some notable triumphs."

Quoted by Venton were Jeff Sheehy, a member of the CIRM governing board; Melissa King, field operations manager for the campaign and executive director of the nonprofit Americans for Cures, and David Jensen, author of "California's Great Stem Cell Experiment" and publisher of this blog.

Proposition 14 would save CIRM from financial extinction. It is slated to begin closing its doors this winter as its original $3 billion in funding is running out. The agency was created by Proposition 71 of 2004, which raised high expectations of cures.  Venton wrote,

"Right now the state still owes about $1 billion toward the debt created by Proposition 71. If Proposition 14 passes, the yearly price tag to pay off the new bond would be about $260 million per year for about 30 years.

"Funding needs for stem cell research also are not as acute as they were back in 2004. The federal National Institutes of Health now funds some basic stem cell research, spending about $2 billion a year, with $321 million of that going toward human embryonic stem cell research. And private ventures, like nonprofits started by tech billionaires, are pouring more money into biotech."

Venton wrote,

"Proposition 14 makes it impossible for the state to use profits from its investment on, say, schools or other funding priorities. Instead, any royalties earned must be fed back into programs to make CIRM-funded treatments more affordable. 

"'What it does is it basically takes all of our returns that we get from this and gives it back to the pharmaceutical and biotech companies,' said Sheehy. 'It becomes just a blatant giveaway to these companies when we should be requiring access and requiring fair pricing.'"

King said that "CIRM fills a neglected funding need," Venton wrote.

"'The NIH (federal funding agency) does not fund clinical trials at nearly the rate that CIRM can and has been,' King said.

"She says that's important because of what she calls the 'Valley of Death,' where promising early-stage research frequently fails to translate into promising treatments that can be tested in clinical-stage research. (What works well in a test tube often does not work well in an organism.) This weeding-out process is costly but necessary. And it’s where CIRM focused a lot of its effort."

A Look at What Lies Ahead for the $5.5 Billion California Stem Cell Ballot Measure

Editor's note: This is an extended version of a piece by yours truly regarding the landscape of the ballot campaign for the initiative to refinance California's $3 billion stem cell agency. A shorter version appeared yesterday on Capitol Weekly, the well-regarded, online news service that deals with California governmental and political news. This version includes more on such things as campaign fundraising, justification for the agency and the overall political environment.

A $5.5 billion stem cell bond measure qualified yesterday for the November ballot, but the campaign to win voter approval is facing an array of hurdles that its supporters never envisioned last summer when they were formulating the initiative. 

Call it the Covid-19 crunch. The pressures include a $54 billion hole in the state budget, looming cuts involving schools and medical assistance for the poor, unemployment now standing at more than three million and predictions by the Federal Reserve that things could get worse. Even California’s famed Rosebowl is facing losses of up to $20 million. 

That is not to mention that the wealthy folks who support such things as stem cell research are also feeling a squeeze from Covid. These are the donors who are usually called upon to help finance what is predicted to be a $50 million campaign on behalf of the measure.

All in all, it is not an environment that would seem to support what some will argue is unnecessary spending. 

The initiative is largely aimed at saving the state stem cell agency from financial extinction. Formally known as the California Institute for Regenerative Medicine (CIRM), voters provided it with $3 billion in state bonds in 2004 to finance research and development of stem cell therapies. Today that cash flow is dribbling to an end. CIRM will begin shutting its doors next fall without a major financial infusion. 

Little noticed so far, however, is how the initiative will also expand the scope of the agency and allow CIRM to venture into arenas that some will argue are a bit remote from scientific research. 

Not unexpectedly, the campaign, Californians for Stem Cell Research, Treatment and Cures,” was pleased with placement of the initiative on the fall ballot. The campaign issued a news release quoting Robert Klein, a Palo Alto real estate developer and chairman of the campaign, as saying, “During the past decade, California has made incredibly thoughtful investments and significant progress along our journey to developing therapies and cures, for diseases and conditions like diabetes, age-related blindness, cancer,  epilepsy, Parkinson’s, Alzheimer’s, and heart disease.

He continued, “It is critical to California families that this vital therapy development pipeline continue to be funded. Our state has always been a leader in medical and scientific research and therapy development, ranking second in the world when evaluated as a nation. Continuing to fund that mission is essential to the health of our families while stimulating the economic recovery for California, with good paying jobs, created by this program.”

The news release also quoted Sandra Dillion, a clinical trial participant and cancer patient advocate. She said, “Since I was diagnosed with a rare form of blood cancer in 2006, there has been a tremendous amount of advancement in research and discovery that has allowed me to be here today, sharing my story, in large part due to the California Institute for Regenerative Medicine supporting the science that saved my life.

 “Without California’s investment in advancing stem cell research and cures, I would not have the same energized, healthy life that I have been able to once again experience.”

The Center for Genetics and Society in Berkeley, Ca., which opposed the 2004 initiative that created CIRM, offered a different perspective.  In response to a query, Marcy Darnovsky, executive director  of the group, told Capitol Weekly that the initiative “does little to ease the serious concerns about CIRM that have been voiced for years by the Center for Genetics and Society, other public interest advocates, and researchers, and echoed by several policy bodies. 

“It does nothing to address CIRM's built-in conflicts of interest, or its lack of legislative oversight -- despite it being an agency supported wholly by public funds. The new proposition makes some things worse; for example, it outsources critically important decisions about ethical standards to an unaccountable national committee. 

“While stem cell research is valuable, there are no longer federal limits on its funding, which was the justification in 2004 for asking California voters to allocate the first multi-billion-dollar pot of money. In the meantime, that campaign's shameless over-promising and hype set the stage for the hundreds of under-regulated commercial stem cell clinics now offering unapproved ‘treatments’ that have caused tumors and blindness.  

She continued, “Today, California faces an enormous budget deficit and proposals to slash high-priority social programs that benefit all of us. It remains to be seen whether voters will approve a new multi-billion-dollar measure for CIRM, instead of investing in healthcare, housing, jobs, education, and other pressing needs.”

CIRM declined to comment on the announcement that the measure had qualified for the ballot. The agency’s governing board is scheduled to discuss  the initiative at a meeting Friday and approve a contingency plan if it fails to pass. 

California is still only beginning to reckon with the economic impact of Covid crisis on services ranging from schools to health care for the poor.  Gov. Gavin Newsom has already announced a $54 billion shortfall in the budget. Lawmakers this week sent him a budget for the next 12 months that papers over the worst problems and assumes the federal government is likely to help out later this year, perhaps during the fall election season. 

If federal funding fails to surface, the fate of the ballot measure could become entangled in voter concern over public priorities. Some voters are likely to ask: Should scientists at well-endowed Stanford University, which is the No. 1 recipient of CIRM funding ($388 million in all), receive more millions while poor people throughout the state are squeezed still further on health care?

One CIRM director, Jeff Sheehy, who has served on its governing board since day one, recently raised scientific and public policy questions. In a May email to the California Stem Cell Report, he said, “I'm not sure that the board has a clear, coherent view of the scope of CIRM's research.  And I am not sure the board has a clear idea of what the scientific mission of CIRM should be in the event that new funding comes from the voters.

"I would note as an aside that CIRM has never submitted its scientific program, including all grants made and their impact, to a rigorous, independent scientific review.  In short, I don't think we really know at CIRM where we've been and where we want to go.  We have anecdotes…."(The ellipses are Sheehy’s.)

The multibillion dollar size of the measure -- $7.8 billion with interest payments on the bonds -- is only one financial issue for the initiative’s backers. In 2017, Klein estimated the cost of the campaign at about $50 million, but has more recently declined to update that figure. The 2004 campaign cost about $34 million. 

Paying for all the accoutrements of a campaign seeking the favor of 20 million voters -- TV ads, website, direct mail, etc. -- will require major campaign contributions at fa time when even the wealthy are feeling the Covid crunch. The financial markets, where much of the wealth of the well-to-do resides, are erratic and more than usually unpredictable. Even prior to Covid, an effort by CIRM to raise $200 million in private funding was unsuccessful. 

At the same time, biomedical companies are increasingly interested in stem cell product development, which they shied away from in 2004.  Just this spring, Gilead Sciences, Inc., of Foster City, Ca., bought a firm backed directly and indirectly by CIRM with $45 million. The purchase price was $4.9 billion, a deal that would have been unheard of in 2004. 

 The agency saw the deal as a validation of its judgment and work, a reason for Californians to vote to sustain CIRM’s operations. But others see the rising private sector investment as easing the need for additional funding from California taxpayers. 

The changing nature of the political scene on a national level could also come into play in the fall. In 2004, also a presidential election year, conservative and fundamentalist forces that might have launched a strong anti-stem cell campaign were more focused on re-electing George Bush. This year a strong California turn-out against President Trump could mean more support for the stem cell agency. Gone too are the Bush administration restrictions on federal funding of human embryonic stem cell research, a rallying cry in the 2004 campaign.  

Klein has said he has a poll that shows that 70 percent of Californians support stem cell research. But he has declined to provide a copy of the poll or provide the name of the firm that performed the work. 

 

One of the products that CIRM has supported successfully over the years is hope. Indeed, its new slogan in 2018 was “Something Better Than Hope.” It was emblazoned on the CIRM annual reports in 2018 and continues to appear on CIRM documents.

The agency has a flock of videos of patients appearing at its meetings over the last 15 years and asking for more research. It gives them hope, they say, during the sometimes tearful, emotional appeals. They are powerful presentations that are available on the Internet and are likely to generate support from many voters. 

To date, the agency is helping to support 63 clinical trials, a number that Klein and CIRM supporters would have scoffed at in the early days. The total cost of trials is high and even the $3 billion goes only so far. Clinical trials are the last and key stage before the Food and Drug Administration approves a stem cell treatment for widespread use. The 2004 campaign raised expectations that such treatments were just around the corner. So far, that has not proven to be the case. Nor has the agency yet generated a stem cell treatment that can be used widely.

Society’s experience with Covid-19, however, could generate a positive sentiment for more research aimed at treating the full array of afflictions that bedevil us. The campaign makes it clear on its home page that is the goal and promise of the stem cell initiative -- “to accelerate development of treatments and cures for life-threatening diseases and conditions that affect someone in nearly half of all families.

It is a “motherhood-and-apple pie” argument that is hard to disagree with. November 3 will tell us whether the voters of California do. 

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'Less Than a Drop in the Bucket' -- Dueling Perspectives on California's First Stem Cell Royalty Check

California is counting its first royalties from a 13-year-old effort to develop stem cell cures and has declared that it hopes that the check will be the first in a flood of payments.

Others, however, warn of the dangers of over-excitement about the $190,345.87 payment from the City of Hope, saying that it is "less than a drop in the bucket" compared to the cost of the $3 billion California Institute for Regenerative Medicine or CIRM, as the state stem cell agency is formally known.

Here is a longer look at the two perspectives in the wake of Monday's royalty report.

John McCain, Washington Times photo

 The royalties were generated from a $5.2 million award in 2012 to the City of Hope for research involving a potential therapy for glioblastoma, one of the deadliest forms of brain cancer and the type afflicting U.S. Sen. John McCain. 

"A little piece of history" is how Kevin McCormack, senior director for communications for the  stem cell agency, described the royalty in an email. He also wrote on the agency's blog,

"It’s the first of what we hope will be many such checks, helping repay, not just the investment the state made in the field, but also the trust the voters of California showed when they created CIRM."

McCormack continued,

"Maria Millan, CIRM’s President & CEO, says the amount of the payment is not the most significant part of this milestone – after all CIRM has invested more than $2.5 billion in stem cell research since 2004. She says the fact that we are starting to see a return on the investment is important and reflects some of the many benefits CIRM brings to the state."

Asked for comment on the payment, John M. Simpson of Consumer Watchdog in Santa Monica, Ca., who was deeply involved in the development of the agency's initial intellectual property rules, said,

“Once again it’s clear that Proposition 71 (the ballot initiative that created the agency) was oversold by its sponsors. Despite campaign hype, it’s only now that we are seeing the first royalty payment and a rather modest one at that."

Bernard Munos

Bernard Munos, a senior fellow at FasterCures. a think tank aimed at speeding medical research, elaborated at more length in his response to a query by the California Stem Cell Report. He said,

"The $200,000 check from City of Hope should be acknowledged, but it only represents 0.02% of the $1.1 billion in royalties that were promised to California taxpayers -- and does not even cover the annual salary of CIRM’s part-time vice chairman.

"It is also unclear how the licensing (by the City of Hope) of a discovery to a New York-based company, Mustang Bio, Inc., will generate jobs and investment in California, as proponents of CIRM originally promised voters. 

"The world has changed since 2003 when George W. Bush severely restricted government-funded research on embryonic stem cells. The Obama administration lifted those restrictions, and regenerative medicine has diversified into many lines of research that have taken the field well beyond the embryonic vs. adult stem cell debate of the early days, which gave CIRM its initial impetus. Looking ahead, it is unclear whether CIRM still has a role to play. 

"Regenerative medicine offers enormous promises, and Californians may indeed want to leverage that opportunity by supplementing federal funding with their own. We have proposed a way to do this, as an alternative to developing plans to extend CIRM with another $5 billion in California bonds, to be paid out of the state’s general fund. 

"Whenever a multi-billion dollar fund is created, it tends to attract all kinds of people who want a piece of it. Unless strong governance is in place with clear rules on how the money must be disbursed, some of it is likely to fund projects that don't get the scrutiny they should, or even lie outside the organization's remit. Inadequate governance has been a problem at CIRM, as documented by reports from the Institute of Medicine -- now the National Academy of Medicine -- and others. Before consenting to an extension of CIRM's mandate, Californians should look at the returns they have gotten, and are likely to get (or not) from CIRM's past investments, and should demand an independent assessment of whether these investments are consistent with what they were promised and with CIRM's mission."

Marcy Darnovsky, FIXED photo

Marcy Darnovsky, executive director of the Center for Genetics and Society, in Berkeley, Ca., said in her email,

"Many Californians voted to establish CIRM because they believed the promises that its backers were making: that we'd soon see revolutionary medical breakthroughs, that our state would get back a billion dollars or more in royalties, that the agency would be run by an 'independent' board. Almost a decade and a half later, none of that has come to pass. 

"The rules and regulations about royalty returns to California are confusing and unclear, and need to be made far more transparent. But it's hard not to ask whether this first royalty payment is anything other than theater, meant to assuage and allure voters now that CIRM is talking about another ballot measure for $5 billion more from the public purse.

"The royalty check from City of Hope is less than a drop in the bucket. It's almost as if you loaned someone $3000 (at your own expense) because they promised to do some good work and pay you back $1000. Years later, they haven’t finished the work but they are offering you twenty cents instead of $1000, and asking for thousands more."

The debate over what Millan has called the "value proposition" of the agency's work is likely to intensify over the next two years. CIRM expects to run out of cash within that period and is pinning its hopes for survival on a proposed $5 billion ballot initiative on the November 2020 ballot -- a campaign that should excite some considerable interest if it is not heavily overshadowed by the presidential election that year.

The $22,000-an-Hour California Stem Cell Story: Rosy Expectations, Fuzzy Future

Evangelina Padilla Vaccaro
CIRM photo

Highlights
Trump and state bond issue?
More than 60 clinical trials projected

No therapies yet for general public
Siren appeal for reseachers
$2.2 billion out the door

Evangelina Padilla Vaccaro – a pink bow in her hair – was likely the first four-year-old ever to address the leaders of California’s $3 billion stem cell research program.

“Thank you,” she whispered. Her mother said more: "Thank you for keeping my family complete." 

Alysia PadillaVaccaro’s voice cracked, and tears flowed on that cool December morning at the meeting at an Oakland hotel.

Evangelina had much to be thankful for. She was born with “bubble baby” syndrome, which meant that she had no functioning immune system. Scientist Donald Kohn of UCLA cured her of the rare affliction by using her own blood stem cells to alter a troublesome gene. It was an experimental treatment not readily available to the public at large. Kohn’s research has been heavily supported with nearly $52 million by the state stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM) .

Evangelina’s story is just what Californians hoped for when they created the Oakland-based agency in 2004 via Proposition 71. Voters were told that stem cell therapies would ease afflictions found in nearly 50 percent of California families. The agency would create the “cures for tomorrow,” said then Gov. Arnold Schwarzenegger.

Since its first awards in 2005, the agency has given away money at a rate of $22,000 an hour, seven days a week, 24 hours a day. But it has yet to come up with a therapy that reaches the general public despite rosy expectations raised by the ballot campaign.

Today, the future of the program is unclear. The agency calculates that it will run out of cash in just three years. Whether it lives on could depend on the likelihood of another multibillion-dollar bond issue, not to mention the success – or the lack of success – of as many as 60 or more clinical trials and even the policies of the newly elected president of the United States, Donald Trump.

Stem cell therapies, it turns out, are expensive and difficult to bring to market, and their use may be

Shinya Yamanaka, UCSF photo

limited to a handful of diseases. On Monday, Nobel Prize winning stem cell scientist Shinya

Yamanaka said as much in an interview with Wallace Ravven of The New York Times. Because of a wide variety of constraints, he said, 

“We can help just a small portion of patients with stem cell therapy.”

In this context, heartwarming stories of patients such as Evangelina could be some of the strongest selling points for CIRM’s continued existence. They could fire the enthusiasm of voters and embolden businesses to partner with CIRM to bring therapies into the marketplace. The number of these emotional stories is increasing.

Evangelina was not alone at the CIRM meeting last month. Three more patients stepped up during a look at the agency’s performance. They included a 22-year-old man, also with a rare, immune-deficiency disease, a paralyzed 19-year-old man and a 70-year-old cancer patient -- all of whom had experienced major improvements during clinical trials. All told, the agency has pumped $113 million into the research that has benefited the four patients.

Evangelina’s story had special significance for Jan Nolta, head of the UC Davis stem cell program.

Jan Nolta, UCD photo

Nolta began her career working with Donald Kohn at Childrens Hospital in Los Angeles in early research involving the “bubble baby” affliction.

“CIRM has funded Don’s continued work in this area, and he has now functionally cured over 20 children with this disease,” she said in an email. “These kids now need no expensive medicine and treatments to keep them alive. They are functionally cured.” 

In Evangelina’s case, she was able to join her fraternal twin sister, Annabella, in living a normal childhood.

CIRM funding has also fueled the growth of the UC Davis stem cell program, which barely existed prior to creation of the stem cell agency. Today Davis has chalked up $129 million from the agency. “We have 16 stem cell or regenerative medicine clinical trials ongoing or recently completed, with more than 20 in the pipeline,” Nolta said.

Davis ranks as the No. 5 recipient of funds from the agency, trailing only such institutions as Stanford, $314 million; UCLA, $269 million; UC San Diego, $170 million, and UC San Francisco, $139 million.

Nolta is one of a number of researchers attracted by CIRM, lured by the cash and research environment created by the stem cell agency. program. She returned to California from Washington University in St. Louis. (See the full text of Nolta's remarks here.)

The appeal of the California largess was highlighted last week by George Daley, dean of the Harvard Medical School.  He was quoted in a lengthy piece about San Francisco Bay Area biotech written by STAT news service editor Charles Piller.

"'I’ve been looking at this from the outside, and franly have been very envious as a scientist based in Massachusetts,' Daley said. CIRM funds have turned many research centers in California, including UCSF, into world leaders in stem cell science, he said, adding: 'I heard the siren song of CIRM early. I considered making a move,' as did more than two dozen of his Harvard stem cell colleagues."

Since CIRM’s inception, it has awarded $2.2 billion to 853 California researchers and institutions. It estimates that it will award another $692 million before money runs out. This year it plans to give away $328 million.  (The awards are separate from the agency’s operational budget, which is capped by the ballot initiative and is about $19 million for the current fiscal year.)

Like most other recipient institutions, UC Davis has representation on the CIRM governing board. The California Stem Cell Report, which has monitored the agency since 2005, has calculated that about 90 percent of the agency’s cash has gone to institutions with links to past or present board members. Those members are barred from voting on awards to their institutions, but they do vote on the nature of the award rounds and approve the rules.

Concerns about conflicts of interest have long been a bugaboo for the agency. Last September,The Sacramento Bee reported that its former president, Alan Trounson, received $443,500 in total compensation after being named in 2014 to the board of directors of StemCells, Inc., of Newark, Ca. Trounson’s appointment to the company’s board came only seven days after he left the agency at the end of June 2014.

Randy Mills, FDA photo

Trounson was replaced by C. Randal Mills, who had been president of Osiris Therapeutics, Inc., of Maryland. Under Mills’ leadership, Osiris was the first company in the world to commercialize a stem cell drug, qualifying it for use in Canada.

Mills and the CIRM team – currently comprised of 48 people – re-crafted the agency’s objectives and established measurable benchmarks for success, winning board approval for what Mills called radical change. The results were summarized at last month’s board meeting and in the 2016 annual report. They included:

• Over the last two years, the agency has helped to finance 27 clinical trials and is looking for another 40 by 2020. (Clinical trials are the last stage before a therapy is approved by the Food and Drug Administration (FDA) for widespread use. Only one out of 10 conventional drug products emerge successfully from the trials.)

• More than 250 projects are currently being managed by the CIRM team.

• Twelve "world-class" research facilities have been created over the last 12 years.

• Three Alpha Clinics, intended to be one-stop stem cell centers, are in operation. A fourth is scheduled for this year.

• A $30 million stem cell "pitching machine" to speed clinical trials and help guide development through federal regulations began operations in 2016.

Nonetheless, development of stem cell therapies -- much less cures -- is a risky business and could be stymied by a number of issues. The agency itself acknowledges risk factors that include reluctance by businesses to invest in stem cell therapies and safety concerns, including the possible death of a patient in a clinical trial.

Mills makes a practice of presenting risk, an innovation at the agency, as he offers up new programs to its governing board. In the annual report, he quoted the poet T.S. Eliot as saying,

“Only those who will risk going too far can possibly find out how far one can go.”

The agency has experienced a few hiccups since Mills arrived. He acknowledges he is still working hard on attracting businesses to partner with scientists to turn their research into cures. 

An ambitious effort to create a unique, public-private, $150 million enterprise to develop stem cell therapies and cures stumbled late last year when no qualified applicants surfaced from the private sector. The agency hopes to recast the proposal in such a manner that it will find a partner.

One of those watching the agency since its beginning is Hank Greely, director of the Center for Law

Hank Greely, Stanford Law photo

and the Biosciences at Stanford.

He said in an email,

“CIRM has been spending money from Proposition. 71 for about 10 years. Once initial hopes of finding low-hanging fruit disappeared, this kind of slog toward treatments became inevitable.  (Although, in biomedicine, 10 years is not (Greely's boldface) a long time - see the 35 plus years it has taken gene therapy to get to the edge of an FDA-approved product.)

“The next few years should determine just how good California's investment has been. It is encouraging to see CIRM supporting so many clinical trials; it will be much more exciting when – and I do expect ‘when’ and not ‘if’ – one of those trials leads to an approved treatment.” 

John M. Simpson of Consumer Watchdog of Santa Monica, Ca., has also observed the agency for years. He said in an email,

“CIRM’s fundamental problem is that supporters of Proposition 71 wildly oversold what passage of the measure would deliver. Voters were led to believe that miraculous cures were just around the corner if only the proposition passed.

“CIRM-funded research has made important contributions to science, but has yet to deliver what voters were promised,” Simpson said. He added that agency management has improved under the regime of CIRM Chairman Jonathan Thomas and Mills “and the most blatant conflicts of interest were mitigated after the scathing Institute of Medicine report.”

In 2012, the highly respected Institute of Medicine, in a $700,000 report commissioned by the agency, recommended sweeping changes at CIRM to deal with conflicts of interest, its dual executive arrangement and the composition of its governing board. The CIRM board initially greeted the report coldly but made some changes to deal with the critical findings.

California patient advocate Don C. Reed, who campaigned for stem cell research long before CIRM surfaced, however, hailed the agency's work as already saving lives and creating hope for millions. He said in an email it was a "quiet triumph" that can be built on. (See here for full text.)

Simpson, who was heavily involved in development of the agency’s intellectual property policy,

John M. Simpson
 Consumer Watchdog photo

raised questions about the failure of the agency to generate the $1.1 billion in royalties for the state promised by its backers. Simpson said,

“The CIRM annual report cites the number of ‘inventions’ CIRM has funded — more than 180.  What share of royalties have taxpayers received as a result? Anticipated revenue from CIRM-funded inventions was a big selling point for Proposition 71.”

(See here for the full text of Simpson's comments.)

 Ironically, another selling point for the ballot measure came inadvertently from former President George Bush, who had restricted federal funding for human embryonic stem cell research. Backers of the ballot measure said it was needed to compensate for Bush’s action. His restrictions were lifted by President Obama. But many researchers are worried that the Trump administration will once again limit federal support for stem cell research.

Stanford’s Greely said,

“The election of Donald Trump and the continuation of a Republican-controlled Congress could create an increased need for extending CIRM.  If the federal government pulls out of some research on basically religious grounds, California may want to step in again.  It depends both on exactly how restrictive the federal government becomes and, more subtly, on how promising the stem cell trials appear.

“I suspect some federal funding restrictions are inevitable but their scope is unpredictable. As to the trials, if they are tremendously exciting, private funds might take over; if they flop, state funds may not be appropriate.  But if the results are very promising but not spectacular, more state funding might be invaluable.” 

(For more on a possible bond election and Trump's position, see here, here, here and here.)

Simpson has another view. He said,

“No doubt CIRM-funded research has made some important contributions to scientific knowledge. The results, however, in no way justify another bond issue to fund the agency.  If CIRM continues after the current funds run out, it should be financed like any other state agency— out of the state’s operating budget approved by the Legislature on annual basis. CIRM’s operating budget could also be augmented by private contributions.”

Mills avoids public discussion of such things as bond measures. But at a meeting last fall, he likened the research program to a “giant flywheel.”

“It takes a long time to get started, and you move it imperceptibly. Once that thing gets turning, it's almost impossible to stop.”

(Editor's note: A shorter version of this story can be found in the print edition of The Sacramento Bee for Jan. 17, 2017, and also on The Bee's website. The full text of various comments follows this story, which also has links to them. Greely's complete comments were included in the article above.)

(On Jan. 19, STAT news carried a lengthy piece on the agency that said it was slow in financing clinical trials, a major factor that has hampered development of a therapy.)

(An earlier version of this item also incorrectly stated Evangelina's age.)

Trump: Helpmate to the $3 Billion California Stem Cell Agency?

Donald Trump's victory last night, oddly enough, could be good news for the future of the California stem cell agency. 

It could be George Bush all over again.

How does that work, you may ask? Trump is a bit of a blank slate on stem cell issues. He has not addressed them directly. But he is pro-life, a fact being celebrated this morning in the usual pro-life venues.

Given that stance, he is likely to reverse the federal government's current funding of human embryonic stem cell research. It would be easy to do, basically nothing more repealing an executive order or issuing a new one.

Such a move would echo the Bush restrictions on human embryonic stem cell research that provided the justification for the 2004 ballot initiative that created California's $3 billion stem cell research effort. Bush's opposition energized the scientific and patient communities on behalf of the initiative.

His opposition also helped to raise the $34 million for the electoral campaign that spawned the California Institute for Regenerative Medicine (CIRM), the official name of the stem cell agency.

Bush provided a big target for supporters of stem cell research. (See here and here.) He embodied the essence of the "anti-science" crowd. And in politics it is good to have a "demon" that can easily be understood. It simplifies issues, sharpens the focus and stimulates voters.

The stem cell agency is now on track to run out of money in 2020 for new awards. CIRM relies on state bonds for its cash but its ability to issue them is coming to an end. No additional source of funding has been identified.

Assuming Trump bans federal research on human embryonic stem cell research, it would bring new life to the possibility of another multi-billion dollar bond issue in the next few years. A new "demon" would surface. All the agency needs to do now is to come up with a high-impact therapy that would resonate with California voters.

Monty Python, $3 billion and Stem Cells in the Golden State

Inquisition scene from Monty Python, photo CIRM/Daily Mail

The headline today from California was nearly irresistible:

"The Spanish Inquisition and a tale of two stem cell agencies"

Not only that, but the headline appeared over an article involving Monty Python, the $3 billion California stem cell agency and the lesser,  $38 million United Kingdom's Regenerative Medicine Platform(UKRMP). 

The "Inquisition" article ran on the California agency's blog. The author was Kevin McCormack, senior director of communications for the California Institute for Regenerative Medicine(CIRM), as the agency is formally known. 

His topic? How the UK and California efforts have performed, according to an article by Stanford's Irv Weissman and Fiona Watt of King's College London, who is a member of the CIRM scientific advisory board, currently "on hold," according to McCormack.  The Watt-Weissman piece was recently published and buried behind a paywall in Cell Stem Cell.

McCormack noted that the article cited location and politics as important in both operations. He wrote, 

"CIRM was created by the voters of California in 2004, largely in response to President George W. Bush’s restrictions on the use of federal funds for embryonic stem cell research. UKRMP, in contrast was created by the UK government in 2013 and designed to help strengthen the UK’s translational research sector....

"Inevitably the two agencies took very different approaches to funding, shaped in part by the circumstances of their birth – one as a largely independent state agency, the other created as a tool of national government.

"CIRM, by virtue of its much larger funding was able to create world-class research facilities, attract top scientists to California and train a whole new generation of scientists. It has also been able to help some of the most promising projects get into clinical trials. UKRMP has used its more limited funding to create research hubs, focusing on areas such as cell behavior, differentiation and manufacturing, and safety and effectiveness. Those hubs are encouraged to work collaboratively, sharing their expertise and best practices."

Irv Weissman, photo wapiti-waters

Weissman and Watt said it was "not unexpected" that CIRM still has not produced a therapy for widespread use. They cited the sometimes decades-long time frame for transforming basic research into a therapy.

Which is where Monty Python comes in, said McCormack. The two scientists picked up a famous line from the British comedy series:

“Nobody expects the Spanish Inquisition – because our chief weapon is surprise.”

Fiona Watt, photo Watt Lab

McCormack wrote,

"They use that to highlight the surprises and uncertainty that stem cell research has gone through in the more than ten years since CIRM was created. They point out that a whole category of cells, induced pluripotent stem (iPS) cells, didn’t exist until 2006; and that few would have predicted the use of gene/stem cell therapy combinations. The recent development of the CRISPR/Cas9 gene-editing technology shows the field is progressing at a rate and in directions that are hard to predict; a reminder that that researchers and funding agencies should continue to expect the unexpected."