Watch What I Do...

With its most recent round of grants – the first for 2013 – the California Institute for Regenerative Medicine (CIRM) continues its transformation from being one of the world’s leading funders of human embryonic stem cell research (hESCR) to one that increasingly supports non-embryonic research alternatives.

In March, CIRM awarded $32 million under three categories of awards.  No funding went to hESCR.  Instead, all of the funding was awarded to programs to promote research using induced pluripotent stem cells (iPSCs).

A grant of $16 million was given to a program to produce 9,000 iPSC lines for use in research on various diseases.  This is in vivid contrast to a previous round of grants, in 2008, also to generate stem cell lines for research.  Then, 16 projects were selected for funding: eight projects were for generating hESCs (5 of these projects also involved iPSCs) while the other eight were for projects involving iPSCs alone.   Now, with this current round of grants, it appears CIRM no longer sees any value in the creation of new hESC lines.

Something similar occurs with another of the March grants, a $10 million award to create a bank to store, grow and make available iPSC lines to researchers. That CIRM has not done the same to establish a bank to house hESC lines would seem, again, to indicate that CIRM finds little value in doing so.  Indeed, as noted in a previous blog, one of the nation’s leading embryonic stem cell banks, the University of Massachusetts Stem Cell Bank, closed its doors in 2012, just four years after its creation was approved.  According to news reports, it had become “obsolete.” 

The remaining grant money was dispersed among 7 projects to produce disease specific iPSC lines.  This is an area where iPSCs have clearly proved their utility in helping to develop therapies, while regular adult stem cells are far ahead in terms of direct clinical use in patients.  Producing iPSCs from cells donated from a patient (a patient with diabetes, Parkinson’s or heart disease, for example) allows scientists to observe the origin and growth of that particular disease and to test drugs to treat it.

There is the old saying “Watch What I Do, Not What I Say.”

Proponents of hESCR can still talk a good game on the supposed ongoing “need” for hESCR.

But when it comes to actually doing the research that has the goal of producing cures and therapies, more and more researchers and institutions, such as CIRM, are turning to induced pluripotent and adult stem cell research and other non-embryonic alternatives.

 After all, talk is cheap, but research costs money and its supporters want results.

Continuing to Ignore Their Own Advice -- Despite Continued Advances

A study in the current issue of  Stem Cells Translational Medicine reports the use of  neural stem cells derived from induced pluripotent stem cells (iPScs) to treat amyotrophic lateral sclerosis (ALS, also known as “Lou Gehrig’s Disease”) in rats.  The study shows that the iPSc-derived neural cells were able to engraft, survive and develop into mature neural cells in the spinal cords of the ALS rats.

Dr. Roland Pochet of the Universite Libre de Bruxelles in Belgium, who headed up the research teams, said the results “demonstrate proof-of-principle of survival and differentiation of human iPSc-derived neural progenitors in in vivo ALS environment, offering perspectives for the use of iPSc-based therapy in ALS."

Dr. Anthony Atala, editor of the journal in which the study appeared, called the results “encouraging,” adding that beyond ALS they “suggest the potential of cell therapy for the field of neurobiology and disease treatment."

The announcement of the study’s results also noted that neural cells had previously been derived from neural stem cells (NSCs) and embryonic stem cells (ESCs) as well.

But this development again demonstrates that along with adult stem cells, iPScs are proving to be viable, ethically non-contentious alternatives to the use of human embryonic stem cells; in this instance the adult and iPSc-derived neural cells did everything the hESCs did, but without having to destroy an embryo in the process.   Indeed this and other studies show the continued pursuit of hESCR is ethically unjustified even by standards first set by its proponents.

In 1999, Presidents Clinton’s National Bioethics commission (NBAC) first recommended federal funding for hESCR.  The supposed potential of the research deserved federal support, NBAC argued -- but on condition.  Given the inherent ethical problems, NBAC judged it was “justifiable only if no less morally problematic alternatives are available for advancing the research (at pg. 53).”  In others words, if viable, ethically non-contentious means existed for advancing such research and pursuing cures, then hESCR should not be pursued at all.

Induced pluripotent stem cells are already replacing the use of hESCs in several areas of research in the filed of regenerative medicine, such as in disease modeling and drug testing.   As noted in a previous blog, the California Institute of Regenerative Medicine, established to give priority funding to hESCR, has over the years been shifting more and more resources into adult stem cell and iPSC research.

Given these developments and others like it, one wonders: why do proponents of hESCR continue to ignore the very standards they set down in the 1999 NBAC report for pursuing it?

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.

An Era Ends Before It Even Begins

To paraphrase an oft-cited verse of T.S. Eliot’s, “this is the way the experiment ends.  Not with a bang but a whimper.”

The experiment was Geron’s highly touted clinical trial using human embryonic stem cells (hESCs) to treat patients with spinal cord injury (sci), for which the FDA gave approval in January, 2009.  The experiment certainly began with a bang, arriving with the usual media hype that human embryonic stem cell research (hESCR) has enjoyed over the years. 

“Some people think this is the dawn of a new era,” ABC’s Diane Sawyer gushed on Good Morning America.  The Los Angeles Times agreed with Sawyer’s talking points, similarly gushing that the trial was “ushering in a new era in medicine.” 

Well, that “new era” in medicine lasted not quite two years, which must be some sort of record for brevity in defining an “era.”  On November 14^th of this year, Geron announced it was shutting down its human embryonic stem cell program.  During this brief “era,” 5 sci patients received infusions of hESCs (Geron originally intended to treat 10 patients total for the trial).  While there were no serious adverse side effects, there has been no evidence of any benefits to the patients either. 

Geron cited financial difficulties as the reason for shutting down the program.  So how did market watchers react to that?

The Street.Com reacted by selecting Geron’s announcement to terminate its hESCR  program as one of the “Five Dumbest Things on Wall Street” for the week of November 18.  It deserves to be quoted in full:

“3. Geron's Bluto Moment

You think John "Bluto" Blutarsky from Animal House had it bad? He saw only seven years of college go down the drain. Biotech bust Geron squandered 21 years of shareholder hopes, dreams and dollars on a wasted education. Shares of Geron fell 21% to $1.74 Tuesday as a result of its decision to shut down its embryonic stem cell research program in order to focus on its experimental cancer drugs. John Scarlett, Geron's newly appointed CEO, insisted in interviews Monday that the company's decision to exit the stem cell business was not an indictment of the entire field but was more a company-specific business decision. Frankly, Scarlett, we don't give a damn how you spin it, but Geron will always be an embryonic stem cell company. For more than two decades, Geron has been sucking money from investors' wallets like a Hoover vacuum with the sole intent of turning embryonic stem cells into new tissue or organs. And now you want to drop it like a bad habit? And after all that preaching about how this technology will help paraplegics walk, cure diseases like diabetes and Parkinson's and prevent heart attacks -- not to mention an accumulated deficit of nearly $700 million -- now you want to try something new? No way, dude! You can't simply change your major like an aimless college student trying to delay graduation. Your parents -- or in this case, your shareholders and investors -- deserve better. Not that they have seen much of a return on their money so far. To date, only four paralyzed patients have received injections of embryonic stem cell-derived nerve cells into their spinal cords. And while no safety problems have been reported, Scarlett admitted that there were "no signs" the stem cell therapy was helping patients either. Still, that's no reason to abandon hope and to change course after all these years of trying. Remember, Bluto spent all those years in a filthy, idiotic fraternity and then went on to become a member of the U.S. Senate. Wait, maybe that's not the best analogy.  But you know what we mean.”

For years, Geron cynically manipulated investors with carefully timed but nonetheless deceptive media announcements that its hESC clinical trial for spinal cord injury was imminent.  Here’s a partial chronology of how Geron did this, as compiled by DNH founding member David Prentice, PhD: 

18 March 2002
University of California, Irvine Prof. Hans Keirstead announces he will ask university officials to seek the U.S. Food and Drug Administration's approval to test human embryonic stem cells on human patients with spinal cord injuries. Initially, Keirstead said he might be ready to take this step in about a year.
22 February 2004
"The company believes it will be cleared to start the first stem-cell therapy in human tests next year, possibly for spinal-cord injury."
1 December 2004
According to Geron CEO Thomas Okarma, the company is aiming to file an investigational new drug application with the U.S. Food and Drug Administration (FDA) requesting permission to begin clinical trials using glial cells derived from embryonic stem cells to repair damaged spinal cords in 2005 or early 2006.
5 February 2005
"Next year [Hans Keirstead] and his corporate partner, Geron, plan to try treating people who have recent spinal cord injuries, in what would almost certainly be the first human trial of any therapy derived from such cells.
19 April 2005
Thomas Okarma, Geron's CEO, is even less convinced that larger animal studies are necessary before testing Keirstead's technique in humans. During an interview at a conference, he said he believes the clinical trial could begin in mid-2006.
9 September 2005
"Geron plans to begin clinical trials on acute spinal cord injury treatment in early 2006, according to chief executive officer Tom Okarma."
7 November 2005
"[R]esearchers at Geron of Menlo Park want to take the next step - in people. They hope to get federal permission to inject those cells into damaged spinal cords. The procedure - which Geron intends to do next year - would be the first human tests of a treatment derived from human embryonic stem cells, the highly versatile body cells that can be coaxed into becoming almost any tissue in the body."
29 March 2006
Tom Okarma: We will complete our IND-enabling studies, which are now in process and still on track, and file our IND during the fourth quarter of this year, assuming the preclinical data continue to go well. That starts a 30-day review clock by the FDA, who then has 30 days to either accept our IND and allow us to proceed or, at that point, they have questions that we must answer before we can begin. We are on track for that. So, assuming they bless the IND, we would hope to be in the clinic in the first quarter of (2007).
17 June 2006
"I'm confident that we will be in the clinic next year with the first human ESC-derived product," said Tom Okarma, chief executive of Geron, at a conference in London last week.
27 July 2006
The company will apply for approval to start US clinical trials in 2007, using glial cells derived from human embryonic stem cells to treat spinal injuries.
4 August 2006
One company, in particular, Menlo Park, CA-based Geron, is taking the lead in developing experimental embryonic stem cell therapies and hopes to begin human trials next year.
9 May 2007
"The first clinical trial of embryonic stem cells is on track to start early next year on patients with spinal cord injury. Geron, the California-based biotechnology company, will carry out the study on accident victims in six trauma centres across the US."
20 July 2007
"Geron Corporation in Menlo Park, California, expects to start clinical trials of a therapy for spinal cord injury early in 2008, according to spokesperson David Schull."
31 October 2007
Geron, based in Menlo Park, Calif., has been using rats in its experiments of a potential treatment for spinal cord injuries. Geron has already met with the FDA and will submit its plans for human testing to the agency by the end of this year, according to Sion.
13 November 2007
Geron's development plan for the product calls for the filing of an Investigational New Drug (IND) Application with the U.S. Food and Drug Administration and, pending the agency's review, initiation of human clinical trials in 2008.
13 November 2007
Geron's development plan for the product calls for the filing of an Investigational New Drug (IND) Application with the U.S. Food and Drug Administration and, pending the agency's review, initiation of human clinical trials in 2008.

15 May 2008
The Geron Corporation announced Wednesday that its plans to begin the first clinical trial using embryonic stem cells had been delayed by federal regulators. While companies typically do not announce when they submit an application to begin a trial for an investigational new drug, the F.D.A.'s action means Geron must have submitted its application in the last 30 days, Mr. Benjamin said.

17 October 2008
But the FDA is nearing the end of its review process and may lift the hold and allow clinical trials to commence within the next three months, Okarma told The Scientist.

20 October 2008
A clinical trial that would test the use of embryonic stem cells to treat spinal cord injury could begin within three months.

In sum, Geron’s behavior over the years is emblematic of the way hESCR proponents have tried to advance their cause: year after year after year, promise major medical breakthroughs with, in the end, little or nothing to show for it. 

In addition to the market, other observers saw other forces at play in the demise of Geron’s hESC trial.  According to Datamonitor Expert View: “Although many would say that Geron's decision reflects the worsening economic environment, in which biotechnology companies are increasingly struggling to raise capital investment, Datamonitor believes that the underlying reasons for the announced divestment actually relate to clinical and intellectual property roadblocks facing Geron's stem cell programs... Geron's divestment highlights the potential pitfalls associated with specific types of stem cell technologies - namely, embryonic stem cells (emphasis added).”

In marked contrast, Datamonitor went on to observe, “adult stem cell therapies continue to race ahead.” 

As Geron’s great new era of medicine was closing with a (media) whimper, the Discovery Institute’s Wesley Smith noted the media’s double standard in the way it covered Geron’s failure vs. advances with adult stem cells.

“You would think Geron’s failure would be very big news,” Smith wrote in the Weekly Standard.  “Instead, it turns out that the mainstream media pay attention only when embryonic stem cell research seems to be succeeding—so far, almost exclusively in animal studies.  When, as here, it crashes and burns, it is scarcely news at all.”

Citing, for example, the attention the Los Angeles Times gave to the FDA’s approval of the Geron trial in January 2009, and then again when the first patient actually received a transfusion of hESCs in October, 2010, Smith noted: “During the same period, however, the paper did not report the encouraging results of early human trials of treatments for spinal cord injury developed using adult stem cells.”

On that Good Morning America show cited above, Sawyer asked Sean Morrison, PhD, a researcher at the Howard Hughes Medical Institute: “What about it, Dr. Morrison? Do you think it could have been done with adult stem cells?”

Morrison replied: I don't think there's any adult stem cell that's ready for use in clinical trials that could be used to do what Geron is doing with these [embryonic] cells.”

How to explain such a remark?   Ignorance?  A willingness to mislead?

In 2005 – four years before the FDA approved Geron’s trial – Dr. Carlos Lima of Portugal published a report in the peer-reviewed Journal of Spinal Cord Medicine showing positive results from a “pilot clinical study” that used adult stem cells derived from olfactory mucosa to treat sci patients  (Lima subsequently published a second study on the use of olfactory mucosa derived stem cells to treat sci patents in the peer-reviewed Neurorehabilitation and Neural Repair, 9/30/09). 

Even earlier, in 2002, reviewing the positive results of using such stem cells in animal models, the Federation of American Societies for Experimental Biology declared : “These results are the most dramatic functional and histological repair yet achieved after complete spinal cord transaction in mammals, and they open new avenues in the search for treatment of spinal cord injuries in other mammals, including humans.”

Finally, and perhaps most important, a word about the patients.  They are the ones who have been the most ill-served by all the media hype surrounding Geron’s “new era” of medicine and hESCR in general.  They have also been ill served by the corresponding willingness of the media and even many researchers to downplay the very real and ongoing advances with adult stem cells.   

There is still great hope and promise for stem cell research to help patients. 

As the Geron example shows, don’t go looking for human embryonic stem cell research to fulfill it.  That hope and promise are being realized with adult stem cells.

Simpler, Better

The New Scientist recently ran a rather remarkable editorial, “In praise of stem cell simplicity.”

“We should keep all avenues of stem-cell research open but be grateful when simpler alternatives emerge,” the editorial asserts.  Pointing to recent advances using adult and induced pluripotent stem cells (iPSCs), the article says these “could spawn novel, personalized stem-cell treatments that, if not simple per se, are simpler than what has gone before.”

Not only are these advances simpler (compared to using human embryonic stem cells (hESCs) to try and treat disease), but “[w]hat marks these treatments out is that they are eminently practical and ethically unquestionable. This is in stark contrast to much previous work, which has focused on human embryonic stem cells, or hESCs.”

Drawing out that contrast, the article notes that hESC research has always been ethically questionable.  It then refers to the so-called “breakthrough” in October using cloning to produce human stem cells.  However, the article notes, the process still required eggs, an embryo was still killed and the resulting stem cells were genetically malformed, “rendering them useless for medical uses.”  Three strikes and that so-called breakthrough is out.

The article specifically refers to two advances demonstrating how non-embryonic stem cell research is simpler than and superior to hESCR.  “Diabetic rats cured with their own stem cells” tells how researchers transformed brain stem cells that had been extracted through the nose into insulin producing cells in the pancreas.”  The researchers did this “without genetic trickery.”

The second advance tells how scientists used stem cells taken from a baby’s own amniotic fluid to repair congenital defects such as holes in the diaphragm.

So it would certainly appear clear that non-embryonic approaches to stem cell research are turning out to be simpler and more effective in terms of actually producing therapies than hESCR.  Despite these advantages, however, the article concludes by calling for all avenues of stem cell research to continue.  For instance, the article notes, iPSCs are reprogrammed using a virus and the reprogrammed cells do not yet match embryonic stem cells.

However, the process of producing iPSCs has vastly improved in the relatively short time since they were first discovered in 2007.  Researchers have used a particular RNA viral vector that carries no risk of integrating into the host genome, to produce iPSCs that have no foreign gene insertions and that are viral/factor-free.  The researchers reported that “the resulting iPSCs expressed human embryonic stem cell markers and exhibited pluripotency.”  Another study has found that proteins produced by iPSCs and human embryonic stem cells (hESCs) are 99 percent similar.  According to one of the researchers the study suggests that iPSCs and hESCs are quite similar.  “According to some measurements, the protein production of an embryonic stem cell was closer to that of an IPS cell than to a second embryonic stem cell. “

As the Do No Harm Coalition has frequently pointed out, in 1999, when President Clinton’s National Bioethics Advisory Committee (NBAC) first recommended federal funding for hESCR, it did so conditionally: “In our judgment, the derivation of stem cells from embryos remaining following infertility treatments is justifiable only if no less morally problematic alternatives are available for advancing the research…The claim that there are alternatives to using stem cells derived from embryos is not, at the present time, supported scientifically. We recognize, however, that this is a matter that must be revisited continually as science advances.” (Ethical Issues in Human Stem Cell Research, Volume I, p.53, emphasis added).

In other words, they recognized that, given the ethical problems associated with hESCR, it should not be undertaken if viable alternatives exist.  

Such viable alternatives exist.  Advances in non-hESCR to treat disease are many, ongoing and well documented in the peer-reviewed literature.  It’s time that proponents of human embryonic stem cell research revisit, in the light of scientific advances, their earlier premature judgments on the need to pursue such destructive research.

Are they really still bothering with That?

In 2007, the world was introduced to induced pluripotent stem cells (iPSCs).

With this breakthrough, Somatic Cell Nuclear Transfer (SCNT) -- more commonly known as cloning -- suddenly looked to be the Dodo bird in the field of stem cell research and regenerative medicine.

But human cloning for research has staged a mini-comeback recently, attended by the usual media hype that always seems to accompany any development in embryo-destructive stem cell research. 

In a 10/6/11 article published in Nature, scientists reported that they had, for the first time, successfully generated a line of stem cells from a cloned human embryo.

Numerous media outlets hailed the news as a “major breakthrough” for stem cell research that had, according to CBS, “scientists buzzing.”  “May lead to cure for Parkinson’s and diabetes” declared the (London) Independent. 

But for all the buzzing and talk of cures on the horizon, the stem cells harvested from the cloned embryo were therapeutically useless.  Dr. Scott Noggle, co-author of the Nature article announcing the “breakthrough” admitted as much: "These cells are not therapeutically relevant at the moment," he stated.  The cells were, in fact, abnormal, given the way that Noggle and his colleagues carried out the SCNT procedure. 

Typically, the SCNT procedure entails removing the nucleus from an egg, thus removing its genetic material.  The nucleus from the donor’s somatic cell is then inserted into the enucleated egg and stimulated to begin development of the cloned embryo. This is the process used to create Dolly the sheep, but it has never been successful in producing a viable human embryo.

The success reported in Nature changed this procedure by inserting the nucleus of the donor’s somatic cell into an intact egg, i.e., an egg that still contained its nucleus.  While  viable (for purposes of harvesting stem cells) embryos were produced, because the egg’s nucleus was not removed the embryos were abnormal, as they contained an extra set of chromosomes, as did the stem cells harvested from those embryos.  Thus, the cells could serve no therapeutic purpose.  "These are grotesquely abnormal cells, so they have no clinical applications. Even scientifically they are of questionable value," said Maureen L. Condic, an associate professor of neurobiology and anatomy at the University of Utah.

In truth, news of this supposed “breakthrough” came across as tired and stale, especially in light of the fact that scientist are currently producing patient specific, fully pluripotent  stem cells without having to create and destroy embryos -- iPSCs .  

IPSCs are ordinary somatic cells, such as a skin cell, that have been reprogrammed into a fully pluripotent state, like an embryonic stem cell.  Among the great benefits of this breakthrough in reprogramming cells is that it gives researchers a ready and virtually unlimited supply of pluripotent stem cells without having to destroy human embryos.  Nor would women be subject to health risks and exploitation because of the large number of eggs necessary for research cloning.

Moreover, iPSCs are patient specific, i.e., they share the same genetic material with the donor of the reprogrammed somatic cell.  For many, the ability to generate patient specific stem cells for transplant was the holy grail of stem cell research.  The whole point behind cloning for research was to generate such cells by using SCNT to create an embryo that was the virtual genetic duplicate of the patient, and then destroy that embryo for his or her stem cells.    

With the advent of iPSCs, cloning for research became all but obsolete.  No less than Ian Wilmut, the scientist most associated with cloning for his role in creating Dolly the sheep, announced he was giving up on SCNT research to pursue iPSC research instead.  And the California Institute for Regenerative Medicine, established by voter referendum in 1997 with a 10 year, $3 billion budget and a mandate to give preferential funding to human embryonic stem cell research (hESCR), including cloning for research, has been noticeably stingy in grants given to the latter (in fact, the number of grants CIRM has given over the years to adult stem cell research projects has proven greater than those for hESCR and SCNT).

No doubt the idea of cloning will continue to provide fodder for science fiction writers and their fans well into the future.  And it will keep some researchers buzzing.

But the supposed potential of human cloning for research to be a practical, therapeutic tool to actually help treat patients, already seems like a thing of the past.