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 stemcells,” the (Worcester) Telegram-Gazettebreathlessly
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.
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.
[1]Testimony before the Senate Committee on Appropriations, Subcommittee
on Health, 9/14/00
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.
[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.
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.
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 14th 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 stemcell 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 stemcell 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 stemcell 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 stemcells 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 stemcell-derived nerve cells into their spinal cords. And while no safety problems have been reported, Scarlett admitted that there were "no signs" the stemcell 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 Medicineshowing 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).
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.
“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.”
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.
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.
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.
Late August saw another round of grants from the California Institute for Regenerative Medicine (CIRM).
CIRM, you may recall, was established by a voter-approved referendum in 2004, with a $3 billion budget (plus another $3 billion in interest) over 10 years. Its mission was to fund stem cell research, with funding preference to go to human embryonic stem cell research (hESCR) and to human cloning for research.
But as the late August grants (again) show, things have not turned out as anticipated.
This round of grants is intended to encourage researchers to form teams in an effort to quicken the time frame for translating research into actual clinical trials. As CIRM put it, the grants would encourage “the most promising approaches towards and into early phase clinical trials.”
So what are these “most promising approaches” to actually producing early phase clinical trials, especially in terms of CIRM’s mandate to give preferential treatment to hESCR and human cloning for research?
Well, projects involving adult stem cells were preferred over those utilizing embryonic stem cells – and by a whopping 3 to 1 margin.
In total, CIRM handed out 19 grants amounting to $1.8 million in preliminary funding (a second round of grants will be worth up to $20 million each). Of those 19, 16 involved the potential therapeutic uses of stem cells (other proposals addressed other research areas, such as proposals to study cancer stem cells). Of those 16, 12 involved proposals to use adult stem and other non-embryonic stem cells to treat heart disease, Huntington’s and Alzheimer’s, among others. Eleven will use actual adult stem cells, while 1 will use non-embryonic induced pluripotent stem cells (iPSCs).
Only 4 of the approved grants were for projects using hESCs. No grants were awarded to research using cloned human embryos.
This latest round of grants actually continues a pattern that has been developing for some time at CIRM.
In October, 2009, a major round of CIRM grants totaling some $230 million went to 14 research projects – but only 4 of them involved the use of hESCs. The rest, again, went to research using adult stem cells or more conventional approaches, such as drugs to treat cancer.
The irony of an institute founded to give preferential support to hESCR and human cloning for research instead giving such extensive support to adult stem cell research was not lost to observers at the time.
“In something of an irony, little of it is going to the reason the institute exists - to work with human embryonic stem cells,” the Knight Science Journalism Tracker commented.
The San Diego Union-Tribune noted: “One irony of the latest grants is that much of the work they support does not involve human embryonic stem cells, a contentious area because it requires the destruction of embryos. Bush administration funding restrictions on that work were a big reason the California institute was launched to begin with, but many of the current projects use less-controversial adult stem cells”.
And the New York Times said that the large number of grants to adult stem cell research compared to embryonic is a “tacit acknowledgment that the promise of human embryonic stem cells is still far in the future.”
While CIRM’s favoring of adult stem cell research may be ironic, it is nonetheless understandable. CIRM knows it needs to show some tangible results to California taxpayers for what will eventually be their $6 billion investment in stem cell research.
Hype -- especially the hype over ESCR that played such a large role in CIRM’s creation – will only get you so far. And as it noted in handing out the current round of grants, CIRM gives priority to those project which seem the “most promising” to actually result in clinical trials.
Once again, adult stem research is proving the most promising approach toward achieving both these goals.
And the promise of hESCR still remains “far in the future.”
A student who was doing a project on stem cell research emailed DNH a series of questions, one of which was “Is there any scientific reason to not continue with stem cell research?”
It seems like a reasonable question, given that stem cell research – or, more correctly, human embryonic stem cell research (hESCR) -- is and remains very controversial.The controversy arises over the ethics of destroying human embryos for research, which is the necessary basis of hESCR.But, the questioner wanted to know, what about the science? Are there any scientific reasons for ending hESCR?
After some thought though, it becomes clear that the student’s question is based on a misguided assumption, but one that nonetheless has underlined much of the debate over the propriety of pursuing hESCR.This assumption is that “science” is the ultimate arbiter of what “science” should or should not do.Throughout the national debate on hESCR we frequently heard the argument that we should be “guided by the science” in determining whether the research should receive federal funding, and that those outside the scientific community had no business telling scientists what they could or could not do.The ultimate logic of this assumption is that scientists should have the final say on what research projects to pursue, whatever – or in spite of— the ethical objections, however sound, other voices may raise.
The title pretty much tells the story.The article highlights seven proposed experiments that -- from a purely scientific perspective -- would benefit us and add to our store of knowledge, but would not (at least at present) be undertaken because of the ethical objections they raise.
For example, one experiment calls for testing potentially toxic substances in human subjects, rather than in animals.The benefits from such an experiment should be obvious – as should the ethical objections to it.Another experiment calls for inserting a “reporter” gene into an embryo in order to directly observe the process of how genes turn on and off and guide the development of the embryo from just a few cells into a fully differentiated human.“If ethics weren’t an issue” the author notes, the knowledge gained from such an experiment could provide a real boost to the field of regenerative medicine. Yet another experiment proposes to breed a human-chimpanzee hybrid.The experiment could help answer many questions surrounding evolution and the origins of humans.The late biologist Steven Jay Gould called such a proposal “the most potentially interesting and ethically unacceptable experiment I can imagine.”
All of these proposed experiments are as scientifically sound as they are ethically unsound.All of them, from a purely scientific perspective, make sense, are designed to be carried out as efficiently and effectively as possible, and would add to our store of knowledge and even result in tangible benefits such as preventing and treating disease.
So, if we were guided first and foremost by science, we would be doing these experiments.But because of the ethics, we do not.In other words, while science may be competent to tell us what we are able to do, and the most efficient way to do it, it is not within the competence of science to tell us what we should or should not do.That judgment must come from outside of science.
The same is true for human embryonic stem cell research.Which is why the argument that we should let the “science” determine whether or not to pursue hESCR is so misleading and disingenuous.As the examples from Wired show, science can make no such determination; it can only come from disciplines outside of science.
During one of the many Congressional hearings on stem cell research, Dr. Stuart Newman, a professor at New York Medical College, laid out the following scenario: in addition to human embryonic stem cells there is another class of pluripotent stem cells called human embryonic germ cells (n.b., Dr. Newman’s testimony [3/5/02] was given before the discovery of induced pluripotent stem cells [iPSCs]).“On purely scientific grounds,” Newman noted, “embryo germ cells show even greater promise than embryo stem cells.”However, while embryonic stem cells are typically harvested no later than seven days after conception, embryonic germ cells are derived from eight to nine week embryos.
Deriving cells from such later term embryos would now be a “hot potato” Newman noted, but not for any scientific reason: “I emphasize that all of this makes perfectly good scientific and medical sense. The only thing that stands in the way is the sense of propriety concerning the uses to which developing human embryos and fetuses may be put. Some of you may draw the line at the tiny clump of cells, others at the two-month embryo, still others somewhat short of full term. Wherever each of you decides to leave this particular train, there will be others who will insert their right to take it to the next station” (please note, Dr. Newman favors abortion rights and noted at the outset of his testimony that his views “do not derive from any notion of the sanctity of the embryo”).
“All of this makes perfectly good scientific and medical sense.” In the context of hESCR, letting science lead the way leads to the commodification of human life.It turns human life – and the human embryo is human life – into a commodity to be exploited as a means to what someone else deems a worthy end.And worthy has now come to include something as mundane as desiring smoother skin, as some cosmetic companies now boast the use of fetal cells in their preparations).
If we used the same standard proponents used to justify hESCR – let “science” have the final say – there would be no reason to judge as “creepy” the experiments described in Wired. But they are, as is destroying and exploiting human life as a means to someone else’s potential benefit.
Add hESCR as the eighth experiment on Wired’s list.
Two recent studies have been published which once again highlight the vast potential of induced pluripotent stems cells (iPSCs) to benefit patients, this time patients with kidney disease. Both studies were published in the Journal of the American Society of Nephrology
In the first, scientists at Australia’s MonashUniversity, led by Dr. Sharon Ricardo, extracted human kidney cells and reprogrammed them into iPS cells, which could then be transformed into other kidney cells that could potentially be transplanted to repair the damaged organ.
In the second report, researchers at the ChineseAcademy of Sciences in Guangzhou, led by Dr. Miguel Esteban, found they could gather kidney cells from a patient’s urine and reprogram them into iPS cells. The reprogrammed cells, also, could be transformed into other kidney cells for potential transplant. An additional benefit is that scientists could freeze the urine cells for future use when needed.
Other researchers into kidney diseases hailed the reports. Dr. Ivonne Schulman, an assistant professor of clinical medicine and nephrologist at the University of Miami's Interdisciplinary Stem Cell Institute in Florida, said that "Two papers back-to-back show that two different kidney cell types are able to be reprogrammed…This is very significant." She added: "It could theoretically help all types of kidney disease…it just depends on the ability of these cells to differentiate back into the cell types needed for that disease."
Dr. Jeffrey I. Silberzweig, co-medical director of the Rogosin Institute Manhattan Dialysis Center in New York City, also welcomed the reports: "The idea that you can have the ability to do stem cell transplants during the early stage of kidney disease and regenerate the damaged part of the kidney would be a tremendous benefit for patients and the country as a whole."
In addition to their potential use in transplants, the reprogrammed kidney cells could also be beneficial for disease modeling, to study the origins and development of kidney disease and for drug screening of new medications to treat kidney disease.
Both these studies come soon after a report that scientists working with insulin producing beta cells successfully reprogrammed such cells to become iPSCs, and that these reprogrammed cells were very efficient in producing more beta cells for potential transplant. The researchers believe the reason for such efficiency is because the reprogrammed cells retain a “memory” of their origin as beta cells so they already have an “understanding,” as it were, of their purpose to generate additional beta cells. It may well be that scientists working with the reprogrammed kidney cells will find the same phenomenon at work here as well (see previous blog “Advances in Diabetes Research –Without hESCs”).
Meanwhile, research using human embryonic stem cells (hESCs) to treat kidney disease shows that it has the potential to generate, well, a lot of talk about the potential of hESCs to treat kidney disease…
