Stem Cells That Become Embryos: Cont'd (p. 2 of 4)

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Analysis: Part II

One comment seems to be in order before applying the foregoing scientific considerations to the NIH Guidelines and the recent NIH report on stem cell research. The massive confusion over the scientific facts that has resulted from the stem cell and cloning debates is not simply a reflection of some debilitating lack of scientific consensus on the correct scientific facts all, but rather more the result of extensive efforts, extending over decades, on the part of some unscrupulous scientists and their proponents flooding the market place with erroneous “scientific facts” in order to advance and achieve their own agendas, many having significant financial conflicts of interest in these debates. Given that much is still not known about the intricate details of the development of the early human embryo, much is.

This analysis is an effort to “reconstruct” the well-known, well-documented, well-established, and most current and relevant scientific facts involved in these related issues, in order to bring some sense of clarity and integrity back to these critical scientific debates. Surely public policy should begin with and be based on the most accurate, current and documented scientific facts available. If not, the rationale of not so doing should be presented to and defended before the American people themselves. Why base public policy on false science?

The issues addressed in this report have been fully referenced by the most current human embryology and human molecular textbooks, written by eminent human embryologists whose work is well known and well respected internationally, and who have been publishing these excellent textbooks for decades now—texts which have been fully peer-reviewed by dozens of others in their specialties from around the world. If any “scientific expert” wishes to refute the work of the authors of these textbooks referenced in this analysis, the minimum professional requirement would be to legally require that these “experts” submit xerox copies from the pages of the human embryology and human molecular genetics textbooks from which they are quoting, or which they are using as the basis upon which they are proffering their “expert scientific opinions.” In addition, they should be legally required to defend their “scientific opinions” before the largest assembly of their own professional scientific peers with academically credentialed expertise in these fields, as well as before the American people. To require less, at this stage of these debates, would be inexcusable and negligent. Far too much is at stake.

The same should thus apply to this analysis. If any scientific facts presented here are incorrect, scientifically documented corrections are requested, and would be greatly appreciated.

III. Culture-Produced Human Embryos From Human Embryonic Stem Cells Would Be Human Clones

As documented in Part I of this analysis, when human embryonic stem cells are removed or separated from the intact embryo—called “blastomere separation” and “blastocyst splitting"—they naturally tend to undergo “regulation,” and can revert to new human embryos in culture. This is called “twinning,” and we have empirical examples of natural twinning in vivo with human monozygotic twins. “Twinning” is the classic example of “cloning"—i.e., the duplication or replication of genetic materials in which genetic “copies” of a progenitor are formed. Repeating some of the references on in vivo human “twinning” (emphases added):

“Monozygotic twinning: If the splitting occurred during cleavage—for example, if the two blastomeres produced by the first cleavage division become separated—the monozygotic twin blastomeres will implant separately, like dizygotic twin blastomeres, and will not share fetal membranes. Alternatively, if the twins are formed by splitting of the inner cell mass within the blastocyst, they will occupy the same chorion but will be enclosed by separate amnions and will use separate placentae, each placenta developing around the connecting stalk of its respective embryo. Finally, if the twins are formed by splitting of a bilaminar germ disc, they will occupy the same amnion.” [William J. Larsen, Essentials of Human Embryology (New York: Churchill Livingstone, 1998), p. 325]

” Monozygotic twins and some triplets, on the other hand, are the product of one fertilized egg. They arise by the subdivision and splitting of a single embryo. Although monozygotic twins could…arise by the splitting of a two-cell embryo, it is commonly accepted that most arise by the subdivision of the inner cell mass in a blastocyst. Because the majority of monozygotic twins are perfectly normal, the early human embryo can obviously be subdivided and each component regulated to form a normal embryo.” [Bruce Carlson, Human Embryology & Developmental Biology (St. Louis, MO: Mosby, 1999), 2nd ed., pp. 44-49.]

However, do we have empirical proof that human twinning in vitro could also produce human twins that could be implanted and allowed to develop in vivo, and go to term as well? The evidence is not yet overwhelming. Yet it has already been suggested in a referenced used in Part I that human twinning in vitro can result in the production of born human twins:

In humans, removal of less than half of the cells from an embryo have been documented. No adverse effects were reported when an eighth to a quarter of the blastomeres were removed from an embryo on day 3 after insemination.…Further evidence supporting the viability and growth of partial human embryos is provided by cryopreservation. After thawing four-cell embryos, some cells may not survive, leaving one-, two-, or three-cell embryos. These partial embryos survive and go to term, but at a lower rate than whole embryos.” [Prof. Dr. Mithhat Erenus, “Embryo Multiplication”]

The fact that one group of cells that had been separated from the whole embryo in vitro survived—i.e., the “partial embryo"—would, it would seem, be some empirical evidence that at least one group of separated cells did go through regulation in vitro, became a twin in vitro, was implanted, was allowed to developed in vivo, and was born.

Thus it is at least plausible that new culture-produced human embryos, or twins, could be produced in vitro. If they were, these twins would also be clones, i.e., identical genetic “copies” of their progenitor cells. Therefore their production would constitute human cloning (emphases added):

The term 'clones' indicates genetic identity and so can describe genetically identical molecules (DNA clones), genetically identical cells or genetically identical organisms. Animal clones occur naturally as a result of sexual reproduction. For example, genetically identical twins are clones who happened to have received exactly the same set of genetic instructions from two donor individuals, a mother and a father. A form of animal cloning can also occur as a result of artificial manipulation to bring about a type of asexual reproduction. The genetic manipulation in this case uses nuclear transfer technology: a nucleus is removed from a donor cell then transplanted into an oocyte whose own nucleus has previously been removed. The resulting 'renucleated' oocyte can give rise to an individual who will carry the nuclear genome of only one donor individual, unlike genetically identical twins. The individual providing the donor nucleus and the individual that develops from the 'renucleated' oocyte are usually described as “clones,” but it should be noted that they share only the same nuclear DNA; they do not share the same mitochondrial DNA, unlike genetically identical twins.…Nuclear transfer technology was first employed in embryo cloning, in which the donor cell is derived from an early embryo, and has been long established in the case of amphibia.…Wilmut et al (1997) reported successful cloning of an adult sheep. For the first time, an adult nucleus had been reprogrammed to become totipotent once more, just like the genetic material in the fertilized oocyte from which the donor cell had ultimately developed.…Successful cloning of adult animals has forced us to accept that genome modifications once considered irreversible can be reversed and that the genomes of adult cells can be reprogrammed by factors in the oocyte to make them totipotent once again.” [Tom Strachan and Andrew P. Read, Human Molecular Genetics 2 (New York: John Wiley & Sons, Inc, 1999), pp. 508-509]

Clone describes a large number of cells or molecules identical with a single ancestral cell or molecule.” [Benjamin Lewin, Genes VII (New York: Oxford University Press, 2000), p. 955)]

Therefore, if culture-produced human embryos are formed in the process of the derivation of human embryonic stem cells, then that process would be cloning, and those culture-produced human embryos would be clones.

In short, if the derivation of human embryonic stem cells is achieved by “blastomere separation” and “blastocyst splitting,” and if “blastomere separation” and “blastocyst splitting” are twinning, and if twinning is cloning, then the process of deriving human embryonic stem cells would be cloning if culture-produced human embryos are formed in the process. The NIH Guidelines do not acknowledge that “twinning” is cloning.

The Guidelines also only refer to one method of human cloning i.e., somatic cell nuclear transfer (SCNT). Yet there are other methods of cloning as well. We know, at least, that to be “silent” on an issue in the legislative language means that that issue is not covered by that legislation.

IV. Impact Of Correct Science On NIH Guidelines For Research Using Human Pluripotent Stem Cells

Although the NIH Guidelines acknowledge that the production by IVF of human embryos for use in research would violate the Congressional ban, they argue that the mere use of “stem cells” privately derived from these human embryos would not, “because such stem cells are not human embryos themselves.” ["Summary of Public Comments on Draft Guidelines,” p. 1; and “I. Scope of Guidelines,” p. 7] [NIH Guidelines can be found on-line at: ].

However, as demonstrated in Part I of this analysis, the very process of retrieving these “pluripotent stem cells” from IVF-produced embryos normally and automatically triggers in the cell the natural process of “regulation,” which could result in these separated “stem cells” becoming new embryos themselves in culture. This would be “the production of human embryos for research purposes,” albeit these human embryos would be culture-produced rather than IVF-produced. If this is possible, and if the research were performed, would this not violate the Congressional ban, and thereby render the NIH Guidelines null and void? Indeed, it could set up a perpetual cycle of killing living human embryos for “the advancement of scientific knowledge” and for “curing diseases."

Likewise, any “stem cells” derived from these culture-produced human embryos could also revert to human embryos themselves through regulation, and so on. Would this kind of research also constitute human embryo research, and thus violate the Congressional ban?

Additionally, the phenomenon of natural “regulation” could render most of the research deemed “eligible” by NIH for funding as “ineligible,” according to the restrictions in the NIH Guidelines themselves.

A. “Pluripotent Stem Cell” Research Rendered “Ineligible” for NIH funding

Section III (p. 12) of the NIH Guidelines stipulate those areas of research using “human pluripotent stem cells” that are ineligible for NIH funding. [This list does not address research using “fetal stem cells,” since, as the Guidelines point out, research using “fetal stem cells” is already legal, given the fact that it is derived from “fetal tissue,” and “fetal tissue transplant research” already falls under the protection of federal regulations and statutes]. Given the correct science, most of the research that NIH deems “eligible” in its Guidelines could possibly qualify for inclusion on their “ineligible” list instead, and thus could not receive NIH funding.

For example, (1) the Guidelines state that “research in which human pluripotent stem cells are utilized to create or contribute to a human embryo” is deemed ineligible for NIH funding. However, as scientifically demonstrated in Part I of this analysis, “human pluripotent stem cells” derived from frozen IVF-produced human embryos could revert to being human embryos themselves in culture, containing their own “stem cells” which when separated from these culture-produced human embryos could convert to human embryo themselves, etc. This would constitute research in which human “pluripotent” stem cells “are utilized to create or contribute to a human embryo"—albeit “stem cells” generated from culture-produced human embryos—and thus would be ineligible for NIH funding according to their own Guidelines.

(2) The Guidelines state that “the derivation of pluripotent stem cells from human embryos” is deemed ineligible for NIH funding—the assumption being that the term “human embryo” being used by NIH refers only to frozen IVF-produced human embryos. But has NIH not considered that these “stem cells” are not all “pluripotent,” and could naturally tend to revert to human embryos themselves? And if any “stem cells” were derived from these culture-generated human embryos, this too would constitute research in which “pluripotent stem cells” were derived from human embryos—albeit culture-generated human embryos—and would thus be ineligible for NIH funding according to their own Guidelines.

(3) The NIH Guidelines state that “research utilizing pluripotent stem cells that were derived from human embryos created for research purposes, rather than for fertility treatment” is deemed ineligible for NIH funding. But again, culture-produced human embryos would contain their own “stem cells” which, when separated from these culture-produced human embryos, could revert to being human embryos themselves in culture, and their “stem cells” could be derived from them and used, etc. This would in fact constitute the “creation of human embryos for research purposes.” Thus wouldn't the use of such “stem cells” derived from culture-produced human embryos would be deemed ineligible for NIH funding according to their own Guidelines?

(4), (5), and (6) The NIH Guidelines state that research utilizing human pluripotent stem cells that were derived or used by means of somatic cell nuclear transfer, i.e., the transfer of a human somatic cell nucleus into a human or animal egg, is ineligible for NIH funding. Many questions need to be answered:

First, couldn't one perform somatic cell nuclear transfer (SCNT) with private funding to create a human embryo, and then have that SCNT-produced human embryo's stem cells removed, cultivated, and allowed to revert to culture-produced human embryos? Those culture-produced human embryos could then have their own stem cells removed, and used in research. These NIH Guidelines do not address this very real possibility.

Second, the NIH statement refers only to the prohibition of using “somatic” cells in nuclear transfer cloning. But there is another category of “diploid” cells in the body other than “somatic” cells, i.e., germ-line cells, or the primitive sex cells—precisely those referred to in these debates as “fetal stem cells.” Because these non-somatic germ-line or primitive sex cells are also diploid, they too can be cloned by means of SCNT, or by any other method of cloning, producing human embryos for research. Those culture-produced human embryos' stem cells could be removed, and used in research. Would such research be “eligible” for NIH funding? These Guidelines do not seem to recognize this very real possibility either.

Third, would this “silence” in the Guidelines also allow research involving the transfer of a human germ-line cell nucleus into a “human or animal egg”? The issue of the use of germ-line cells, referred to in these debates as “fetal stem cells,” will be addressed in more detail below. However, within this context of “ineligible research,” it is important to recognize that these “fetal stem cells” could be used for cloning by means of “twinning,” by means of SCNT, as well as by means of DNA-recombinant human gene germ line transfer—a form of “positive eugenics.” In DNA-recombinant gene transfer, the “foreign” DNA is transferred into a gamete or early embryo, and that “foreign” DNA is then replicated throughout succeeding generations of humans. DNA-recombinant gene transfer is considered by human molecular geneticists as a form of cloning of molecules of foreign DNA (emphases added):

“[A] cloning vector is a plasmid or phage that is used to 'carry' inserted foreign DNA for the purposes of producing more material or a protein product.” (p. 956) …[Used in “clonal analysis"]: “Clonal analysis identifies a group of cells descended from a single ancestor in which a transposition-mediated event altered the phenotype. Timing of the event during development is indicated by the number of cells; tissue specificity of the event may be indicated by the location of the cells.” (p. 474) ) [Benjamin Lewin, Genes VII (New York: Oxford University Press, 2000)]

Fourth, and relatedly, the Guidelines only make a restriction on one method of cloning—i.e., SCNT. But what about other forms of cloning, e.g., parthenogenesis, the transfer of mitochondrial DNA, “twinning,” or DNA-recombinant gene transfer to germ line cells or early embryos? The Guidelines do not address the possibility of using cloning methods other than SCNT to produce human embryos whose “stem cells” could then be harvested.

(7) Other supposedly “ineligible research” in the NIH Guidelines is chimera research—i.e., research in which intra- or inter-species of embryos are formed. Virtually any of the kinds of research listed above could be used —sooner or later—for chimera research, other than the one kind of cloning specified in these Guidelines. The NIH restrictions on funding would not preclude any of that research from NIH funding.

(8) Finally, the NIH Guidelines state that “research in which human pluripotent stem cells are used in combination with somatic cell nuclear transfer for the purposes of reproductive cloning of a human” is “ineligible” for NIH funding. However, again, virtually all of the research listed above could be used to create human embryos, “stem cells,” or even human or animal chimeras, for the purposes of reproductive cloning, without the use of the SCNT technique. Yet the NIH Guidelines are silent on those kinds of research as well. Thus those kinds of research could receive NIH funding. Since these Guidelines do not address any other form of cloning except SCNT, all other forms of cloning which could produce embryos, “pluripotent stem cells,” and chimeras for the purposes of reproductive cloning of a human” would be eligible for NIH funding, according to their own Guidelines.

In sum, it would seem that most of the research listed by the NIH Guidelines as “eligible for NIH funding” would in reality be ineligible for NIH funding, even according to their own Guidelines. In addition, much of the research listed by the NIH Guidelines as “ineligible for NIH funding” would be eligible for NIH funding—even according to their own Guidelines—because the Guidelines remain silent on them.

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