Monday, October 26, 2020

Proposition 14: First CEO of California Stem Cell Agency Says $5.5 Billion Stem Cell Measure Not Needed

Zach Hall, UCSD photo
The first president of the California stem cell agency, Zach Hall, says that he would vote against the $5.5 billion ballot measure to save the research enterprise from financial extinction if he still lived in California.

Hall, now retired and living in Wyoming, says a justification for agency existed in 2004 when it was created by voters via another ballot measure, the $3 billion Proposition 71. 

But, according to the new book, "California's Great Stem Cell Experiment," Hall says "that the rationale and need are not so evident today for a state-supported agency dedicated to stem cell research."  

The creation of induced pluripotent stem cells has largely supplanted the use of cells derived from embryos, Hall said. The Bush Administration restrictions on human embryonic stem cell research were major drivers for Proposition 71, but those have now been lifted.

Hall said that the National Institutes of Health could likely support most of the stem cell work that is now backed by CIRM.

Proposition 14, the $5.5 billion ballot initiative, would refill the stem cell agency's coffers. The program is running out of the $3 billion provided in 2004 and will begin  closing its doors this winter without major funding. 

Hall was president and CEO of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, from 2005 to 2007 and drew up the agency's first strategic plan. During his long career, Hall was also director of the National Institute of Neurological Disorders and Stroke in the 1990s, executive vice chancellor at UC San Francisco, CEO of En Vivo Pharmaceuticals and a director of the New York Stem Cell Foundation.

Interviewed for the book, which was authored by this writer, Hall said that he has no regrets about serving as its first president, a job he largely enjoyed. 

Hall said that Proposition 71 of 2004 served an important and useful purpose. It helped to re-energize the stem field at a time when it was “disheartened and demoralized” by the restrictions of the Bush Administration.

While the 2004 measure had significant flaws, he said it was very successful at a critical time in attracting stem cell researchers to California.

“The idea that California would make this sort of commitment, I think, had a huge impact on the field,” Hall said.

 “It's certainly true that because of Proposition 71 that California continues to play a stronger role in stem cell research than it otherwise would have. But, contrary to some expectations, it is not the center of the universe of stem cell research in the same way that Silicon Valley is for information technology.

“It is one of many global centers of excellence for stem cell research. One perhaps naïve expectation that has not been met is an explosion of profitable California biotech companies specializing in stem cell research.”

Hall said, however, that Proposition 14 “is searching for a rationale to continue CIRM.” Hall mentioned the “amorphous” research avenues provided for in the measure: mental health, personalized medicine, “aging as a pathology” and “vital research opportunities.”

“You can use the money for almost anything,” Hall said. “This takes off a lot of the brakes on how the money can be spent.”

Given what has been learned over the last 15 years, he said he would have thought a new initiative would have attempted to improve governance and try to make CIRM work better, be more efficient and more strategic. “There's just no sense of thoughtfulness of using the expertise of getting relevant people together to think about it and come up with a plan,” Hall said.

He also said that Proposition 14 does not provide a good or transparent mechanism for making decisions about how the money is going to be spent.

“My guess is that all the board positions will be filled by constituents, people who depend on CIRM money in some way and who will be very pliable about what is to be done. Exactly the wrong way to do it.”

The California Stem Cell Report asked Hall last week if he would like to add anything to his earlier comments for the book. "One thought I might add," he replied, "concerns the idea that Proposition 14 will address the issue of the 'Valley of Death', i.e. the gap between discovering a possible therapeutic and being able to 'de-risk it' enough to attract the interest of big pharma.  What is being proposed, it seems, is that CIRM wants to act as a kind of VC (venture capitalist) with the state's money.  

"In my view, a much better approach to this problem is to find ways to encourage academic and industry scientists (both biotech and big pharma) to work together starting from an early stage of the work. This has been done effectively (and much more cheaply!) by several private philanthropic organizations.  The Michael J. Fox Foundation and Target ALS are two examples that I know of." 

Sunday, October 25, 2020

Looking for the $700,000, IOM Evaluation of the California Stem Cell Agency? Here is a Good Link

 


In 2012, the prestigious Institute of Medicine published a report on California's stem cell agency after months of studying the research program at a cost of $700,000 to the agency itself.

Directors of the agency had expected that the "gold standard" study would give the agency a seal of approval that would lead voters in California to approve additional billions for the California Institute for Regenerative Medicine (CIRM), as the agency is officially known.

The report by the IOM (now called the National Academy of Medicine) has a number of bad links to it on the Internet, and some persons have reported difficulty in finding it. Here is a link that will take you directly to the study where you can read it free online.

Here is the beginning of an article about the study when it was released on Dec. 6, 2012.

IOM Recommends Sweeping Changes at California Stem Cell Agency

A blue-ribbon study of the $3 billion California stem cell agency today said the program has “achieved many notable results,” but recommended sweeping changes to remove conflict of interest problems, clean up a troubling dual-executive arrangement and fundamentally change the nature of the governing board.

The recommendations from the 17-month study by the Institute of Medicine (IOM) would strip the board of its ability to approve individual grants, greatly strengthen the role of the agency's president, significantly alter the role of patient advocates on the governing board and engage the biotech industry more vigorously.

For more on the IOM report and CIRM's actions on its recommendations, see the new book, "California's Great Stem Cell Experiment: An Inside Look at a $3 Billion Search for Stem Cell Cures."

Proposition 14: The Scientist Magazine Digs into California's Stem Cell Agency and the Ballot Measure

The Scientist magazine yesterday published a more detailed look at the state of California's stem cell agency and a $5.5 billion ballot measure that would send it into arenas that it has previously not explored. 

The article by Katarina Zimmer said the California Institute for Regenerative Medicine (CIRM) has "helped transform its state into an innovation hub of stem cell science."  The article was more complete and detailed than many of the news pieces prepared by California media.

Quoted by Zimmer were stem cell scientists Jeanne Loring, co-founder of Aspen Neurosciences, Inc. of La Jolla; Larry Goldstein of UC San Diego, and Jeff Sheehy, who has served on the CIRM board since its inception in 2004. 

Zimmer also cited the 2012 Institute of Medicine (IOM) study that was commissioned by CIRM at a cost of $700,000. Directors of the agency expected a "gold standard" endorsement of the agency, but the IOM cited significant problems with conflicts of interest on the board. The study also recommended major restructuring of the board and the agency. 

An analysis last month by the California Stem Cell Report showed that 79 percent of CIRM awards -- $2.1 billion -- has gone to institutions that have links to past or present board members. 

Robert Klein, the sponsor of the $5.5 billion Proposition 14, did not include any of the more significant recommendations from the IOM in his 17,000-word, proposed revision of CIRM's legal charter. Klein was a strong advocate for commissioning the study by the prestigious IOM.  Klein was not quoted by The Scientist. 

Zimmer's piece covered many of the arguments pro and con on Proposition 14 that are familiar to readers of this web site. However, her piece is not likely to find significant numbers of readers among California's 20 million voters. Only a tiny fraction of them read The Scientist magazine. 

However, The Scientist does reach a significant number of persons globally that are interested in such things as stem cell research.

For more on the IOM report and CIRM's actions on its recommendations, see the new book, "California's Great Stem Cell Experiment: An Inside Look at a $3 Billion Search for Stem Cell Cures."

Friday, October 23, 2020

Proposition 14: Stem Cell Balderdash at Sacramento Bee

Has California's stem cell program "relieved the suffering of millions?” The Sacramento Bee thinks so, but the assertion is totally false. 

It was contained in an editorial today that endorsed Proposition 14, which would save the state stem cell program from financial extinction along with broadly expanding the scope of the agency, known formally as the California Institute for Regenerative Medicine (CIRM)

The agency was created in 2004 and was given $3 billion that the state borrowed. The cash is now running out. And the agency will begin closing its doors this winter without a massive infusion of money. Proposition 14 provides $5.5 billion. 

During its nearly 16 years, the agency CIRM has not yet funded research that has led to a stem cell treatment widely available to the public and approved by the federal government. 

It has helped to fund 64 clinical trials, which are a necessary prelude to commercializing a therapy. Some 30,000 patients would have to be enrolled in each of those trials to bring the "relieved-suffering" figure to two million.

The “suffering of millions” rhetoric was not the only case where the editorial echoed campaign hype. The Bee also said that the measure would cost only “$5 per person per year for 30 years,”  repeating an unsubstantiated assertion by the campaign. It may or may not be accurate, but it would involve a series of calculations and assumptions that the campaign is unwilling to share with the public. 

The California Stem Cell Report asked the campaign 53 days ago how it came up with the figure. The campaign still has not responded, which is a reasonable indication that the campaign lacks confidence in the number, to put it mildly.   

The editorial is behind a paywall. If you would like to see a copy, please email djensen@californiastemcellreport.com.

Thursday, October 22, 2020

Prop. 14 Media Coverage from Capitol Weekly and California Healthline

The campaign on behalf of a $5.5 billion stem cell ballot measure this week placed an opinion piece on Capitol Weekly, and California Healthline separately offered up a news overview of the proposal, Proposition 14. 

The measure would save the California stem cell agency from financial extinction and broadly expand its scope into new areas ranging from mental health to "aging as a pathology." The agency is running out of the $3 billion that voters provided nearly 16 years ago and will begin closing its doors this winter without a major cash infusion. 

The piece on Healthline referenced the 2004 ballot initiative that created the agency. The article by Rachel Bluth said,
"During that first campaign, voters were told research funded by the measure could lead to cures for cancer, Alzheimer’s and other devastating diseases, and that the state could reap millions in royalties from new treatments.

"Yet most of those ambitions remain unfulfilled."
The article continued,
"The campaigns for both bond measures may be giving people unrealistic expectations and false hope, said Marcy Darnovsky, executive director of the Center for Genetics and Society. 'It undermines people’s trust in science,' Darnovsky said. 'No one can promise cures, and nobody should.'

"Robert Klein, a real estate developer who wrote both ballot measures, disagrees.... He said some of (the agency's) breakthroughs are helping patients right now.'

"'What are you going to do if this doesn’t pass? Tell those people we’re sorry, but we’re not going to do this?' Klein said. 'The thought of other children needlessly dying is unbearable.'"
California Healthline is independently published by Kaiser Health News for the California Health Care Foundation.

The Capitol Weekly piece was written by Tracy Grikscheit, chief of pediatric surgery at Children’s Hospital Los Angeles, who has received nearly $15 million from the stem cell agency. Children's has received more than $32 million from the agency. It has a longstanding relationship with the University of Southern California, which has received more than $114 million from the agency and which has also had a representative on the agency's board for a number of years in the past.

The Capitol Weekly article largely consisted of well-worn information from the campaign for Proposition 14.  Capitol Weekly is an online news service covering state politics and government.

Monday, October 19, 2020

Prop. 14: Online Forum Scheduled for Wednesday on $5.5 Billion Stem Cell Ballot Measure

An online forum dealing with the $5.5 billion stem cell measure to save California's stem cell research program is scheduled for this Wednesday with a panel that includes scientists and patient advocates. 

The event is free and open to the public. It is sponsored by Summit for Stem Cell Foundation, a San Diego-based, stem cell advocacy group. The session will include a live Q&A segment. Questions may also be submitted in advance. 

On tap for the discussion about Proposition 14 are Jeanne Loring, co-founder of Aspen Neurosciences and formerly with Scripps Research Institute; patient advocates Kristin MacDonald and Katie Jackson; Melissa King, executive director of Americans for Cures, and the publisher of this blog for the last 15 years, David Jensen. Moderating will be Bernie Siegel, executive director of the nonprofit Regenerative Medicine Foundation. Siegel created and co-chaired 17 annual World Stem Cell Summits.

Registration is limited. You can register here. The event begins at 5 p.m. PDT and is scheduled to conclude at 6:15 p.m. 

(Editor's note: An earlier version of this item listed Paul Knoepfler of UC Davis as a participant on the panel. However, he has had to drop out.)

Sunday, October 18, 2020

Ballot Campaign Hype and Erosion of Trust in Science

The matter of trust came up last week in an item on the California Stem Cell Report that dealt with the Proposition 14 campaign and how hype can erode the people's faith in science.

The following comment was sent via email by a person very well-versed in science, research and human behavior who, however, must remain anonymous.

"What would be the rationale behind trusting science any more than trusting Google, a cable news network, or politician? 

"Science is the work product of scientists, who are human beings the last time I looked. Inherently interested and incentivized human beings, as we all are. 

"Sure, they often tout themselves as 'independent' or 'neutral and disinterested' parties in this business. But rest assured that is just marketing. For there is lots and lots of money at stake. Money that directly benefits and influences these neutral arbiters of truth in exactly the same way as it benefits and influences the executives at Facebook.

"I'm not criticizing, only pointing out the reality that economic forces, like gravity, apply to everyone. No profession is exempt. In that sense, science is trustworthy. Having been paid for, the outcome is both predictable and assured."

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​A new book about the stem cell agency includes a discussion of trust and the California stem cell agency based on comments from the Institute of Medicine, which performed a $700,000 evaluation of the enterprise. Authored by David Jensen, you can buy the book on Amazon:  California's Great Stem Cell Experiment: Inside a $3 Billion Search for Stem Cell Cures. Click here for more information on the author.

Friday, October 16, 2020

Prop. 14 News Coverage: The 'Nuanced Track Record' of the California Stem Cell Agency



California's $3 billion stem cell agency, which is facing a life-and-death test on this fall's ballot, was described this week as chalking up a "nuanced track record" in an article carried by the online news service CalMatters. 

The article recounted the history of the agency since 2004, when it was created by a ballot initiative, Proposition 71. Today, the agency is running out of money and hopes voters will approve Proposition 14, a $5.5 billion ballot measure that also makes extensive changes in the scope of the agency. Without substantial funding, it will begin closing its doors this winter. 

CalMatters is a nonpartisan and nonprofit online news site devoted to state government and politics. The piece by Barbara Feder Ostrov said,

"This time, embryonic stem cell research is in a much different place, with federal funding no longer blocked and more funding from the biotech industry.

"Voters will want to consider what California’s previous investment in stem cell research has accomplished. It’s a nuanced track record.

"While many scientific experts agree that Prop. 71 (of 2004) was a 'bold social innovation' that successfully bolstered emerging stem cell research, some critics argue that the institute’s grantmaking was plagued by conflicts of interest and did not live up to the promises of miracle cures that Prop. 71’s supporters made years ago. Although the agency is funded with state money, it’s overseen by its own board and not by the California governor or lawmakers."

The "social innovation" comment was contained in a 2012 blue-ribbon study of the agency, commissioned by the agency itself for $700,000. The study also said that the agency has substantial built-in conflicts of interest on the governing board of the California Institute for Regenerative Medicine (CIRM), as the agency is officially known. 

The California Stem Cell Report last month performed an analysis of CIRM awards that showed that 79 percent of the $2.7 billion in grants has gone to institutions that are linked to members of its governing board. 

Ostrov's article additionally said, 

"A June 2020 analysis by University of Southern California health policy researchers estimated that taxpayers’ initial $3 billion investment in the research institute helped create more than 50,000 jobs and generated $10 billion for the state’s economy."

The stem cell agency commissioned the report at a cost of $206,000.

Ostrov noted substantial opposition in editorials in California newspapers. 

"The editorial boards of some of California’s biggest newspapers...have opposed the measure, including the Los Angeles Times, the Orange County Register, the San Francisco Chronicle and the San Jose Mercury News/East Bay Times. The Fresno BeeModesto Bee, and San Luis Obispo Tribune newspaper editorial boards support Prop. 14." 

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Read all about California's stem cell agency, including Proposition 14,  in David Jensen's new book. Buy it on Amazon:  California's Great Stem Cell Experiment: Inside a $3 Billion Search for Stem Cell Cures. Click here for more information on the author.

Wednesday, October 14, 2020

California's Five-Buck Stem Cell Mystery and Prop. 14 Campaign Hype

The campaign to save California's stem cell agency with a $5.5 billion cash infusion is peddling a variety of claims that stretch the facts or that the campaign is unwilling to support publicly.  

Leading the pack is the assertion that the multibillion-dollar proposition will cost no more than a bottle of aspirin per person, per year. Unspecified by the campaign, however, is the number of persons and the number of years. The five-buck claim is clearly an attempt to minimize the cost of the proposal, which actually totals an estimated $7.8 billion, according to the state's legislative analyst. 

Robert Klein, leader of the Proposition 14 campaign, made the five-buck claim back in July. It has also appeared on the campaign web site. And Klein brought up the figure again this month in a radio broadcast.

"Proposition 14 will cost the state an average of less than $5 per person, per year – about the cost of a bottle of aspirin" is the way Klein put it last summer.

The California Stem Cell Report has asked the campaign several times to explain how it arrived at that figure. The first request was made 44 days ago (Sept. 1). The campaign has not responded. 

On Oct. 5, Klein brought up another number during a KQED broadcast. He said $4.1 billion was put into CIRM research in 2019 via matching funds. The state stem cell agency declined to verify that figure. A query to the campaign has not been answered. 

The campaign additionally uses a figure of 90 to describe the number of clinical trials in which the stem cell agency is involved. The agency, which is known officially as the California Institute for Regenerative Medicine (CIRM), says that it is  involved in 64.  That is a more than respectable number, more than Klein would have predicted back in 2005 when he was the first chairman of CIRM.

The campaign's justification for using the larger figure seems to be that somehow, someway, that some piece of CIRM-funded research, however tiny, has played a role in some sort of trial. By that criteria, John J. Loud could be also credited with contributing to a CIRM-backed clinical trial. He invented the ballpoint pen in 1888.  

Over the past several years, the agency, during public meetings, has been careful to limit its focus on clinical trials to those that involve meaningful financial participation, for which it deserves ample credit. (It should be noted that the number has grown as CIRM has helped to fund more trials.) 

Pushing the envelope is normal practice for ballot campaigns. It may be unrealistic to expect the stem cell campaign to behave any differently.  Winning is everything in an election campaign. As I have remarked in the past, a ballot campaign is like a war with a deadline. The losers are like so much charnel on the electoral battlefield.

That said, Proposition 14 involves the credibility of science, a matter much in the news nowadays. And backers of the stem cell initiative continue to suffer from the ill effects of the hype of the 2004 campaign, which was also led by Klein. 

The excessive and unrealized voter expectations raised by 2004 campaign are popping up this year in news stories and editorials about Proposition 14 in a way that does not improve its chances of approval, at least for some people. Of course, constant repetition of misleading or bogus information can have an impact on some voters as the country has seen on a national level. 

Art Caplan, a nationally prominent bioethicist, said in 2014

“Stem cell research seems, again and again, to go off the rails when it comes to the ethics of research.”

Caplan was speaking mainly about hyped claims involving stem cell research that could not be replicated. The general concern, however, remains alive.

In 2016, five researchers highlighted ongoing issues involving stem cell hype in a piece in the journal Science, They wrote,

"This (trend) raises the risk of harmful consequences, including misleading the public, creating unrealistic expectations, misinforming policy debates, devaluing methodical approaches to research, and driving premature or unwarranted clinical use. This is particularly important in light of mounting concern about the marketing of unproven stem cell treatments. This trend may have led to a gap between public expectations and the actual state of stem cell science and clinical development."

More recently in California, Hank Greely, director of Stanford's  Center for Law and the Biosciencesthis week was quoted in an article about Proposition 14.  He said, 

“Politics has a corrupting influence on everything — it pushes toward exaggeration." 

As for what that means for voters evaluating Proposition 14 and the claims of its backers and opponents, the ancient admonition of caveat emptor would seem to be the order of the day -- buyer beware.  That is a deeply unfortunate position for those who believe that the nation should trust science.  

(Editor's note: This is an updated and lightly edited version of an earlier version of this item.) 

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Read all about California's stem cell agency, including Proposition 14,  in David Jensen's new book. Buy it on Amazon:  California's Great Stem Cell Experiment: Inside a $3 Billion Search for Stem Cell Cures. Click here for more information on the author.



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