Another First

This blog has on several occasions noted how the California Institute for Regenerative Medicine  (CIRM) – established primarily to fund human embryonic stem cell research (hESCR)—has instead in recent years been directing more and more of its grants towards adult and other non-embryonic research projects. 

Among the many categories of grants awarded by CIRM is the Disease Team Research Awards.  This category was specifically established to fund projects that have the most promise of actually leading to clinical trails.  The first grants from this category were awarded in October, 2009.  As reported in a previous blog, of the 14 grants awarded, only four went to projects using embryonic stem cells.  In dollar terms, of the $250 million awarded in total, only $71.5 million went to the 4 hESCR projects; the rest went to adult and other non-embryonic stem cell research projects.  Clearly, in 2009 CIRM believed such avenues of research offered far more promise of resulting in clinical trials than hESCR.

And it turns out, that belief was not mistaken.

The first CIRM-funded research project to reach clinical trial was recently announced: to use adult stem cells to treat heart disease.  The researchers had received their funding under the above mentioned October, 2009 round of Disease Team Research Awards.

The FDA approval was a “critical step in testing promising therapies in patients,” Ellen Feigal, MD, Senior Vice President for Research and Development at CIRM, said. “It’s a reflection of the initial progress being made in advancing scientific discoveries towards potential therapies for patients.”

The numbers also tell an interesting story.  The four hESCR projects that received funding during that same October 2009 round of grants received between $15 million and $20 million each.  In marked contrast, the adult stem cell project that first reached clinical trial received far less.  In fact, it received the smallest amount of all the projects funded under this round -- $5.5 million, or three to four times less than the hESCR projects.  Yet it has proved the most promising.

Halfway into CIRM’s 10-year lifespan, some have questioned whether it has a future given the way it has fallen far short of the hype and misplaced promises about therapies from hESCR.  The FDA approval of the CIRM-backed adult stem cell research project is in this regard a much needed first for the Institute.

It just wasn’t a first that hESCR proponents predicted or expected.  

Zero Interest, No Withdrawals

In the classic musical comedy “A Funny Thing Happened on the Way to the Forum,”  the Roman slave Pseudolus tries to convince his master to free him by urging:  “Be the first, start a trend!”

Well, a funny thing has happened to those who started the trend toward that bright future of miracle cures from human embryonic stem cell research (hESCR).

As noted a number of times on this site, the California Institute for Regenerative Medicine (CIRM) -- the nation’s largest funder of stem cell research, founded for the express purpose of supporting human embryonic stem cell research -- has in recent years been directing more and more of its grants to adult and other non-embryonic stem cell research projects… a clear sign that CIRM now sees adult stem cells and other alternatives as far more likely to provide therapeutic benefits for patients than embryonic stem cells..

And as noted in the previous blog, hESCR celebrity advocate Michael J. Fox recently conceded that a cure for his Parkinson’s will in all likelihood come from somewhere other than embryonic stem cells.

Now comes news that the University of Massachusetts Stem Cell Bank will close when it runs out of money at the end of the year.

The reason?  It’s become obsolete, the Boston Globe reports, citing state officials.

The bank was launched with much fanfare in 2008, with a $7.7 million dollar grant from the state government.

“It takes a few seconds to get a glimpse of the precious cargo loaded into the laboratory cooler that Dr. Gary Stein opens, mostly because of the frosty fog that billows out. Then the air clears, and boxes of samples come into view: human embryonic stem cells,” the (Worcester) Telegram-Gazette breathlessly began its report on the bank’s opening.

Like CIRM, the Massachusetts stem cell bank was established as a defiant response to President Bush’s policy of limited federal funding for hESCR.  Also like CIRM, its main emphasis was to be on human embryonic stem cells, in this case their storage and maintenance. 

“Originally, the bank was seen as a repository for embryonic stem cell lines that were being created but were not eligible for federal funding under Bush-era restrictions,” the Globe reports.  The Globe further notes that the bank was “a marquee piece of Governor Deval Patrick’s effort to bolster the life sciences industry” in Massachusetts. 

But today?  Citing Terence Flotte, dean of UMass Medical School, “the bank receives one to two requests a week,” the Globe reports. 

Susan Windham-Bannister, president of the Massachusetts Life Sciences Center, said the bank was “absolutely state of the art” when it first opened.

But if the number of weekly requests just cited is any indicator, today the bank is closing due to a pronounced indifference to what it has to offer – human embryonic stem cell lines. 

Zero interest, no withdrawals.

CIRM, Michael J Fox and now the University of Massachusetts Stem Cell Bank, all rethinking and moving away from hESCR or even closing altogether.

Starting a trend?

Better Late Than Never

Like CIRM, others are rethinking all the hype for hESCR and coming to realize that the real promise of stem cell research in all probability lies elsewhere, in adult and other non-embryonic avenues.

For more than a decade, Michael J. Fox has been a leading celebrity advocate for human embryonic stem cell research.  As the New Scientist recently put it, Fox “was on the front line of the US's ‘stem cell wars’, arguing that embryonic stem cells could cure conditions like his own – Parkinson's disease.”

In testimony before a Senate subcommittee in 2000, Fox referred to the “miraculous potential” of human embryonic stem cells and claimed that the “consistent and inescapable conclusion is that this research offers a potential to eliminate diseases -- literally save millions of lives.”[1]

Fox also was a vigorous advocate for passage of California’s Proposition 71, which established CIRM.  In a commercial he taped Fox declared “[Prop] 71 will support research to find cures for diseases that affect millions of people ... including cancer, diabetes, Alzheimer's and Parkinson's.  Please support the effort to find cures by voting Yes on 71.  It could save the life of someone you love."

But in a recent interview with ABC News’ Diane Sawyer, Fox’s take on the ability of hESCR to deliver cures was far different, as he expressed an outright skepticism that such research will ever live up to its hype– hype that he had a very prominent role in promoting.

Sawyer broached the topic with Fox by characterizing hESCR as “this is the promise, this is the future” (had she been a lawyer and this was a courtroom, that would clearly be called “leading the witness”).

Ten years ago, Fox doubtless would have enthusiastically agreed.  But now, his response was highly qualified and cautious:  “The other avenues of research have grown and multiplied and have become as much or more promising,” Fox replied.  “So an answer may come from stem cell research but it’s more likely to come from another area.”

Those other areas, according to the New Scientist “are speeding towards clinical trials. These include neurotrophic factors – proteins that promote the survival of nerve cells – as well as antibodies that target the alpha-synuclein protein, which may be a cause of the brain damage seen in Parkinson's.”

Proponents of hESCR should have displayed such realism and caution over the last decade in the public policy debate on stem cell research, rather than the hype and exaggeration they resorted to instead.

“It's time to act on what we've learned,” said Mr. Fox in 2000.  “Further delay would come at a high price.”  Treatments from adult and other non-embryonic stem cell research were indeed almost certainly delayed, as public attention and resources were diverted for years toward the largely disappointing avenue of research based on embryo destruction.  Advocates who called for such diversion may now be realizing that it is their agenda that slowed authentic progress.

But as the saying goes, better late than never.

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[1]Testimony before the Senate Committee on Appropriations, Subcommittee on Health, 9/14/00

A Trend Continues...

With its recent round of grants, the California Institute for Regenerative Medicine (CIRM) continues a trend begun several years ago now – increasing support for non-embryonic stem cell research and reducing support for destructive human embryonic stem cell research (hESCR) and research aimed at human cloning.  This trend by CIRM away from embryonic stem cell research is not driven by any ethical concerns—CIRM continues to issue grants for hESCR, only on a far smaller scale than originally envisaged.  CIRM was founded, after all, on the premise that it would give funding priority to hESCR and cloning for research as those were considered the most promising avenues for producing cures.

But since 2004, when California voters approved a referendum establishing CIRM, the evidence for the efficacy of adult stem cells to provide therapeutic benefits for patients has continually increased, while the evidence for human embryonic stem cells to do the same has decreased.  CIRM, for instance, approved a $25 million loan[1] to Geron for that company’s now infamous clinical trial using hESCs to treat spinal cord injury, only to see Geron cancel the trial just over one year after the first patient was treated -- with no evidence of therapeutic benefits to the five patients who received the hESCs (see previous blog, “An Era EndsBefore It Even Begins”).

According to a report in Nature, since October 2011 CIRM has been considering a new 5 year strategic plan that gives funding priority to stem cell research with the best chance of leading to clinical trials.  The new plan, adopted in late May, envisions at least 10 early stage clinical trials within the next 5 years.

Commenting on the shift of emphasis from basic research to preparing for clinical trails,

Deepak Srivastava, a cardiovascular researcher at the Gladstone Institute in San Francisco, told Nature “With their stated goals of getting cures into people, it’s appropriate to shift the balance.”

The latest round of CIRM grants, announced the same day the new strategic plan was adopted, reflects this funding priority of “getting cures to people.”  Of the 21 grants  –totaling $69.3 million – only 6 involve research using hESCs[2]  None of the grants go to human cloning for research.

The remaining 15 grants all go to research using adult stem cells, iPSCs and direct reprogramming of adult cells.  Obviously this funding emphasis -- a lion’s share of $50.9 million --on non-embryonic research reflects a belief that these avenues hold the most promise for producing actual therapies.

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[1] Of the$25 million approved, Geron actually received $6.42 million before cancelling the trial.  The company has repaid the loan in full, with interest.  

[2] One of those six uses [non-embryonic] induced pluripotent stem cells (iPSCs) in addition to hESCs.

Caveat emptor

A recent AP report looks at the California Institute for Regenerative Medicine (CIRM) halfway through its ten year term and asks “is it still relevant?”

The report bluntly notes:

“The taxpayer-funded institute wielded the extraordinary power to dole out $3 billion in bond proceeds to fund embryonic stem cell work with an eye toward treatments for a host of crippling diseases. Midway through its mission, with several high-tech labs constructed, but little to show on the medicine front beyond basic research, the California Institute for Regenerative Medicine faces an uncertain future…will it still exist when the money dries up?

This is in marked contrast to the very rosy predictions that were made in order to sell the institute to California voters in 2004.  Back then, in order to convince voters to approve the establishment of CIRM in Proposition 71 --  at a cost of $3 billion over 10 years, plus interest --  proponents of the measure assured them that not only would human embryonic stem cell research (hESCR) produce all kinds of cures, but those cures would dramatically reduce the state’s healthcare costs and generate substantial royalties for the state.  A report by Stanford University confidently predicted that the research (primarily hESCR) supported by the institute would generate in royalties anywhere between $537 million to $1.1 billion.  Overall, the report predicted a 120 to 236 percent return on the initial investment.

That hasn’t happened and in all likelihood never will. Instead, the money is drying up and CIRM is looking for ways to raise more.

The AP report goes on to ask, “So what have Californians received for their money so far?”  The answer: “The most visible investment is the opening of sleek buildings and gleaming labs at a dozen private and public universities built with matching funds. Two years ago, Stanford University unveiled the nation's largest space dedicated to stem cell research: 200,000 square feet that can hold 550 researchers.”

And what about all the confidently predicted cures?  “There are no cures yet in the pipeline and CIRM has shifted focus, channeling money to projects with the most promise of yielding near-term results.”

Do No Harm has noted before at this blog spot that over the years, CIRM has increasingly moved away from its initial commitment to favor hESCR in awarding grants and toward adult stem cell research – precisely because such research is proving to have “the most promise of yielding near-term results.”

John Simpson of Consumer Watchdog told AP that CIRM is a victim of its early supporters' hype.  “‘The impression you got was, if you just passed this bond measure, Christopher Reeve will be jumping out of his wheelchair and walking next week,’” said Simpson, referring to the late paralyzed actor who appeared in TV ads backing Prop 71. "They're having to live down the super high expectations that they raised."

That hype, however, was necessary to sell such ethically contentious research to the public precisely because it was ethically contentious – hESCR necessarily requires the destruction of human life to proceed.  Caveat emptor.

There is an old adage we all heard from our parents and which we still tell our children today: “If it seems too good to be true, it probably is.”

Regarding hESCR, California’s taxpayers are learning that lesson all over again.