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Posted on July 11, 2014 at 9:49 AM

Last week’s edition of Nature includes developments in the world of stem cell research, also noted in the general press:

First: A group from Portland, San Diego, and Stockholm published work (payment required to read article) seeking to define the “best” human pluripotent stem cells on cellular and molecular grounds.  They compared:

  • Stem cells taken from an embryo, created in IVF and destroyed for the research, presumably the “gold standard” for what embryonic stem cells (ESCs) should be because they ARE such cells;
  • Stem cells taken from embryos created by somatic cell nuclear transfer (SCNT), or cloning, again, created expressly for research;
  • Induced pleuripotent stem (iPS) cells, created by “reprogramming” a mature, differentiated adult cell.

Note that to get the first two requires an egg donor—for IVF in the first place, for egg cytoplasm into which a nucleus from a mature, non-stem cell is transferred.

Key findings:

  • The number and nature of abnormalities in gene copies was similar in all 3; notably, up to 30% of iPS cells had no identifiable genetic abnormalities;
  • The patterns of gene “methylation”—a normal, and critical, chemical modification to DNA that determines which ones are “on” or “off”—were more varied in iPS cells, while the SCNT-derived cells looked more like the ESCs in this regard;
  • The patterns of transcription—how the genes are read—was more often abnormal in iPS cells than in the SCNT-derived cells.  This was consistent with the methylation observation.

The authors did not look specifically at mutations in gene sequences—something that is well within current technical lab capabilities—but said that this should certainly be done in the future.

They concluded that the ESCs derived from cloning look more like those from the IVF embryo, probably because they both use egg cytoplasm, and that is critical to the eventual characteristics of the ESCs.  And they concluded that therefore, ESCs from cloning are going to be better to use in future medical treatments than will iPS cells.

This last claim was criticized as overreach by numerous experts in the field.  In an accompanying News and Views article (also available only for a fee), Vladislav Krupalnik and Jacob Hanna put it better:  it appears that neither the iPS nor the SCNT approach perfectly copies ESCs from an embryo.  They conclude that “scientists and clinicians [should] redefine their quest for perfection as a hung for the adequate, cost-effective, and safe.”

They further point out that SCNT is technically difficult, requires egg donation, and creates “health, safety, and ethical challenges.”

Indeed.  If one grants the moral status of the embryo, as I do, then only the iPS approach offers an ethical means of deriving stem cells for medical treatments or other uses.  And that approach is open to refinement, toward the goal of adequate, cost-effective, safe, and ethical stem cell translational research.

(I won’t delve here into whether it is ethical for me to cite this research, given the embryo creation and destruction it entailed.  If I have transgressed an ethical boundary thereby, I freely did so in search of the broader points here.)

Second:  The journal published retractions of an article, related letter, and accompanying News and Views column, originally published on January 30 of this year, and receiving rather spashy coverage in the general press, to the effect that mature mouse cells could be quite easily “reprogrammed” to be induced pleuripotent stem cells by making only modest manipulations, such as exposing the mature cells to a mild acid bath.  In my post of February 20, 2014, I cautioned that there were already some misgivings about the reports, and that conservative bioethicists should not rush to embrace new reports that imply, much less prove, that human embryonic stem cells will soon be of no scientific or medical interest to anyone, and that should be widely and immediately acclaimed.

Points I wish to make on this:

  • Science must be done ethically; embryos indeed warrant the protections afforded to human research subjects;
  • But an argument from utility is dubious; it is too early to say what the “best” stem cells are for therapy, and the argument is excessively utilitarian;
  • Reproducibility is a hallmark of science.  Without that, one is left with, at most, “natural philosophy.”

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