Monday, January 03, 2005

Another Update on Cloning

The latest issue of the New England Journal of Medicine has an article that clarifies some of the science, as well as the ethical issues, regarding human cloning. 
Human Cloning — The Science and Ethics of Nuclear Transplantation
Rudolf Jaenisch, M.D.
Volume 351:2787-2791         December 30, 2004         Number 27

In addition to the moral argument against the use of somatic-cell nuclear transfer for the creation of a child ("reproductive cloning"), there are overwhelming scientific reasons to oppose this practice. In contrast, many believe that the practice of somatic-cell nuclear transfer with the goal of generating an embryonic stem-cell line (sometimes referred to as "therapeutic cloning") is justified, because it holds the promise of yielding new ways of studying and treating a number of diseases. Once isolated from a patient, an embryonic stem cell thus derived would be "customized" to the needs of the patient who had served as the nuclear donor and thus would obviate the need for immunosuppressive treatment as part of a therapeutic application. In addition, because embryonic stem cells can generate most, if not all, types of cells in vitro, a stem cell isolated from a patient with a complex genetic disease could be used to study the pathogenesis of the disease in culture. [...]
Unfortunately, this article was not published on an open-access basis.  I'm not sure why not; often, they provide open access to editorials of public interest.  On the other hand, it is such a technical article, that it might not be very informative to nonscientists.

Dr. Jaenisch discusses, in detail, the reasons that reproductive cloning is not feasible for the reproduction of humans.  He then discussed the distinction between reproductive cloning and therapeutic cloning.  The latter technique, therapeutic cloning, is more accurately called somatic-cell nuclear transfer (SCNT). 

Figure 1. Comparison of Normal Development with "Reproductive Cloning" and the Derivation of Embryonic Stem Cells through Nuclear Transfer ("Therapeutic Cloning").

During normal development (left), a haploid (1n) sperm cell fertilizes a haploid oocyte to form a diploid (2n) zygote that undergoes cleavage to become a blastocyst embryo. The blastocyst is implanted in the uterus and ultimately develops into a newborn animal. During "reproductive cloning" (center), the diploid nucleus of an adult donor cell is introduced into an enucleated oocyte recipient, which, after artificial activation, divides into a cloned (nuclear-transfer) blastocyst. On transfer into surrogate mothers, a few of these blastocysts will develop into newborn clones, and most will be abnormal. In contrast, the derivation of embryonic stem cells through nuclear transfer (right) requires the explantation of cloned blastocysts in culture in order to derive an embryonic stem-cell line that can be differentiated in vitro, potentially into any type of cell that occurs in the body, to be used in research or for therapeutic purposes.

Without going into too much detail, I'll outline the most important point of the article.  SCNT results in a "cell mass" that does not have the potential to develop into a viable organism.  Cells are removed from this mass to generate the embryonic stem cell lines.

If one accepts that the "cell mass" is not an embryo, then it follows that it is possible to generate embryonic stem cells without destroying an embryo. 

I know, the semantics get kind of confusing.  If there is no embryo, how can the cells be called "embryonic" cells?  The point, though, is that the "cell mass" produced by SCNT at no point has the potential to go on to develop into a viable organism.  Dr. McHugh (link), of the President's Council on Bioethics (PCBE), proposed calling the cell mass a "clonote."  I suppose that would make the resulting stem cells "clonic stem cells" instead of embryonic stem cells.  But for scientific purposes, they would be just as good as embryonic stem cells. 

Since most, if not all, of the objections to the use of embryonic stem cells come from the destruction of an embryo, the use of SCNT would eliminate those objections.

However, one must accept that the "cell mass," or clonote, really is different than an embryo, in some ethically meaningful way.  Dr. Jaenisch explains:
[...] after nuclear transfer, the epigenetic differences established during gametogenesis are subject to erasure, because both parental genomes of the somatic donor cell — not just the sperm genome, as in fertilization — are introduced into the oocyte from the outside and are thus equally exposed to the reprogramming activity of the oocyte cytoplasm. Therefore, in cloned animals, imprinted genes should be particularly vulnerable to inappropriate methylation, which causes abnormal expression — a prediction that has, as noted above, been verified experimentally. For cloning to be made safe, the two parental genomes of a somatic donor cell would need to be physically separated and individually treated in "oocyte-appropriate" and "sperm-appropriate" ways. At present, it seems that this is the only rational approach to guaranteeing the creation of the epigenetic differences that are normally established during gametogenesis. Such an approach is beyond our present abilities, implying that serious biologic barriers (rather than mere technical problems) hinder faithful reprogramming after nuclear transfer and thus preclude the use of nuclear cloning as a safe reproductive procedure.

[...] Indeed, the blastocyst produced by somatic-cell nuclear transfer harbors fundamental biologic deficiencies that preclude its ever becoming a healthy human with any acceptable efficiency. Therefore, we may be justified in distinguishing the embryo produced by in vitro fertilization from the product of somatic-cell nuclear transfer.
The validity of this distinction is discussed further by Dr. Jaenisch on the PCBE site, here

What this shows is that is it important to understand the technical details of the process in order for one to make an informed decision about the moral permissibility of this particular kind of cloning, and the use of this particular kind of embryonic stem cell.  Specifically, it is not valid simply to look at the terms "embryonic stem cell," or "cloning," and render a judgment.  I do not mean to argue that such judgments cannot be made, or that one must accept Dr. Jaenisch's distinction between clonotes and zygotes.  However, one must understand the distinction, even if one does not accept it, in order to make an informed judgment.

(Note: The Rest of the Story/Corpus Callosum has moved. Visit the new site here.)
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