Monday, November 21, 2011

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.

Wednesday, November 2, 2011

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.

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