Stem Cells That Become Embryos: Implications For The NIH Guidelines On Stem Cell Research, The NIH Stem Cell Report, Informed Consent, And Patient Safety In Clinical Trials. Analysis: Parts I And II

Dianne N. Irving, M.A., Ph.D.
Fellow, The Linacre Institute of The Catholic Medical Association
Consultant on Medical and Research Ethics, The Catholic Medical Association USA
Consultant on Medical and Research Ethics, The International Federation of Catholic Medical Associations
Bethesda, MD., July 22, 2001
Reproduced with permission

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“…[F]ederally funded research that utilizes hPSCs would not be prohibited by the HHS appropriations law prohibiting human embryo research, because such cells are not human embryos.” (DHHS General Counsel)

“Although human pluripotent stem cells may be derived from embryos or fetal tissue, such stem cells are not themselves embryos.” (NIH Guidelines for Research Using Human Pluripotent Stem Cells)

Analysis: Part I:

I. Introduction

Question: Can human embryonic and human fetal “pluripotent” stem cells become living human embryos?

The very scientific and legal basis for the NIH Guidelines for Research Using Human Pluripotent Stem Cells (November 21, 2000), as well as for the recent NIH report, Stem Cells: Scientific Progress and Future Research Directions, is the claim that such human stem cells “are not themselves embryos.” Hence, the use of such “stem cells” would not violate the Congressional ban on human embryo research.

However, it if could be demonstrated that human embryonic and human fetal stem cells, once separated from the whole intact human embryo, not only can but indeed naturally tend to become new living whole human embryos per se (which would then also be cultivated and killed in research), then these accurate objective scientific facts alone would render both the NIH Guidelines and the recent NIH Report null and void. NIH would in fact illegally be allowing the “creation of a human embryo or embryos for research purposes.” (§ 511(a)(1)).

If such objective scientific facts could be demonstrated, they should be responsibly and swiftly acknowledged by this administration, including the DHHS and the NIH. The NIH Guidelines should be rescinded, and the moratorium on the use of “pluripotent stem cells” should be reinstated, since even their use would constitute human embryo research per se, and thus automatically violate the Congressional ban.

The purpose of this scientific analysis is to demonstrate empirically, scientifically, and beyond any shadow of a doubt, that indeed, once separated from the whole intact human embryo, human embryonic and fetal “pluripotent” stem cells can become new living human embryos themselves, new living human beings—as we already know happens even naturally in monozygotic twinning.

The implications for this simple scientific fact on the scientific integrity of the NIH Guidelines, the recent NIH stem cell report, informed consent procedures and documents, as well as on scientifically responsible and safe applications of “stem cell therapies” to potentially millions of vulnerable human patients in subsequent required clinical trials, will be summarized in this analysis.

II. Scientific Proof: Stem Cells Become Embryos

Answer: Yes—human embryonic and human fetal “pluripotent” stem cells (even as defined in the NIH guidelines and report) can become living human embryos.

There have already been extensive arguments against the NIH Guidelines—arguments which have thoroughly demonstrated that the Congressional ban on human embryo research would be violated because of the source of the “stem cells.” That is, in order to “retrieve” these “stem cells,” living human embryos would be, in the words of the Congressional ban, “destroyed, discarded, or knowingly subjected to risk of injury or death…” (§ 511(a)(2)). Such “retrieval” processes themselves would thus violate the ban.

But what has not been included in the public debates so far, nor addressed by the NIH, is the fact that in addition to human embryos being destroyed as the source of these “stem cells,” these “stem cells” themselves can naturally become living embryos which could also be cultivated and then destroyed during experimentation. That is, once separated from the whole intact human embryo, these separated cells naturally tend to undergo “regulation”—i.e., to “heal” themselves from any injuries, and they then revert to being new living whole embryos—human beings—themselves. We know this from our own observations of natural monozygotic twinning, as well as by simply looking in the human embryology textbooks (emphases added):

“The embryo enters the uterine cavity after half a week,…. Each cell (blastomere) is considered to be still totipotent (capable, on isolation, of forming a complete embryo), and separations of these early cells is believed to account for one-third of cases of monozygotic twinning.” [Ronan O'Rahilly and Fabiola Muller, Human Embryology & Teratology (New York: Wiley-Liss, 1994), p. 23]

“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]

“Early mammalian embryogenesis is considered to be a highly regulative process. Regulation is the ability of an embryo or an organ primordium to produce a normal structure if parts have been removed or added. At the cellular level, it means that the fates of cells in a regulative system are not irretrievably fixed and that the cells can still respond to environmental cues. … Of the experimental techniques used to demonstrate regulative properties of early embryos, the simplest is to separate the blastomeres of early cleavage-stage embryos and ddetermine whether each one can give rise to an entire embryo. This method has been used to demonstrate that single blastomeres, from two- and sometimes four-cell embryos can form normal embryos,….

… Another means of demonstrating the regulative properties of early mammalian embryos is to dissociate mouse embryos into separate blastomeres and then to combine the blastomeres of two or three embryos. The combined blastomeres soon aggregate and reorganize to become a single large embryo, which then goes on to become a normal-appearing tetraparental or hexaparental mouse… Blastomere removal and addition experiments have convincingly demonstrated the regulative nature (i.e., the strong tendency for the system to be restored to wholeness) of early mammalian embryos. Such knowledge is important in understanding the reason exposure of early human embryos to unfavorable environmental influences typically results in either death or a normal embryo. … Some types of twinning represent a natural experiment that demonstrates the highly regulative nature of early human embryos,….… 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.]

Ironically, even the recent NIH stem cell report itself acknowledges this innate and natural capacity of these “pluripotent stem cells” from early human embryos to naturally form whole living embryos themselves (emphases added):

“If these cells separate, genetically identical embryos result, the basis of identical twinning.” (NIH stem cell report, p. A-3)

Three things should be noted from these direct quotations from the human embryology textbooks. First, the tendency of separated individual cells—or even separated groups of cells—to undergo “regulation” and become whole embryos themselves is a natural tendency or property inherent in these separated cells or groups of cells. Second, this ability to “heal” and form new living embryos applies not only to the earliest embryo (e.g., from the 2-16 cell stage embryo which involves “blastomere separation"), but also to the embryo at the blastocyst stage (5-7 days post fertilization which involves “blastocyst-splitting"), as well as to the bilaminar embryo which has already implanted (up to 16 days post fertilization). Third, virtually all of these stages of the early human embryo—from fertilization to just before the formation of the mesoderm (gastrulation)—are included in the definition of “pluripotent” as found in both the NIH guidelines and the NIH stem cell report.

These objective scientific facts are also known by IVF researchers and clinicians, who consider exploiting this natural “healing” tendency in order to produce more embryos for cultivation, implantation and research purposes (emphases added):

“…(2) the fertilized egg, which has not yet divided, is now known as a zygote; (3) the egg begins to divide and is now known as an embryo; at this point each blastomere, or cell, within the embryo, is capable of developing into an identical embryo.” [Geoffrey Sher, Virginia Davis, and Jean Stoess, In Vitro Fertilization: The A.R.T. of Making Babies (copyright 1998 by authors; information by contacting Facts On File, Inc., 11 Penn Plaza, New York, NY 10001), pp. 20]

“In such cases, patients may benefit from embryo multiplication, as discussed in the study by Massey and co-workers. …Since each early embryonic cell is totipotent (i.e., has the ability to develop and produce a normal adult), embryo multiplication is technically possible. …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.…Based on the results observed in lower order mammals, the critical period of development to ensure success in separating human blastomeres should be at the time of embryonic gene expression, which is reported in humans to be between the four- and eight-cell stages. …The second potential method of embryo multiplication is blastocyst splitting. … For couples who have less than three quality embryos for transfer, blastomere separation could be of benefit.” [Prof. Dr. Mithhat Erenus, “Embryo Multiplication”]

Two things should be noted in these direct quotations from IVF sources. First, after separating off the blastomeres of either the earliest cleaving embryo, of the morula, or of the later blastocyst, obviously neither the IVF clinician nor the woman undergoing IVF “therapy” consider that what is being implanted in her uterus are just “stem cells." At least the assumption is that they are living human embryos. Second, most “excess” human embryos produced by IVF are usually frozen down between the 4-8 cell stage (emphasis added):

“Successful transfer of four- to eight-cell embryos… to the uterus after thawing is now a common practice (Fugger et al., 1991) ...” [Moore and Persaud, p. 39]

Thus most of these “frozen IVF human embryos” are clearly not 5-7 day old “blastocysts”—the term used in the debates and in the NIH documents. “Blastocysts” are composed of about 30-150 cells and have distinct inner and outer cell layers; it is from their inner cell layers that researchers supposedly want to “retrieve” these “pluripotent stem cells.” However, most of these frozen embryos are at the cleavage and the morula stages and thus have no inner cell masses It is impossible to derive “stem cells” from frozen IVF embryos which have no inner cell masses.

In fact, the term “pluripotent stem cells” would seem to be nothing more than the latest reincarnation of the now-rejected and scientifically false term “pre-embryo,” used for decades by NIH officials and her researchers to justify the use of these youngest of vulnerable living human beings in destructive research. And like the term “pre-embryo,” there is virtually no scientific basis for the current term “pluripotent stem cells” as used in these NIH documents.

In short, yes—“stem cells” derived from the early human embryo—from the 2-cell stage through the germ line stage (gastrulation)—are not only capable, but are even inherently driven by regulation to “heal” themselves and to form new whole living embryos themselves. Not only do human embryologists know this empirical fact, so also do IVF researchers, clinicians, and their patients.

It is thus difficult to understand why the former DHHS General Counsel did not know these empirical facts, nor the NIH officials who drafted the NIH Guidelines, nor the majority of NIH officials and scientific “consultants” who drafted the recent NIH report on stem cell research (most of whom receive NIH funding for this research). It is also thus difficult to square the incessant discussions in the NIH Guidelines and the recent NIH report about the use of “frozen human embryos” from which to derive “stem cells” (supposedly from their inner cell masses) when by far the majority of these frozen embryos have no inner cell masses.

It is ironically curious, to say the least, that both NIH documents, which already eschew ethical and legal considerations, purport to be presenting and explaining “scientific” facts as their justification, while simultaneously ignoring, or redefining, these most basic and indisputable of scientific facts of human embryology. What possible purpose would they have for knowingly and methodically doing this?

If the scientific and legal basis for the NIH Guidelines is that human “pluripotent stem cells” are “not themselves embryos,” but if it has been empirically and scientifically demonstrated here that all of these “pluripotent stem cells” naturally strive to become and succeed in becoming embryos themselves (which will then also be cultivated and killed), then there is absolutely no scientific or legal basis for the existing NIH Guidelines. Indeed, the very use of such cells would in fact constitute the “creation of a human embryo or embryos for research purposes,” and thus automatically violate the Congressional ban.

The implications of the simple and fundamental scientific facts of human embryology presented in this part of the analysis are quite grave and extensive. The impact on individual sections of the NIH Guidelines, the recent NIH report on stem cell research, informed consent processes and documents, and human patient safety in up-coming clinical trials for “stem cell therapies” will be addressed in subsequent “parts” to follow.

Next page: Analysis: Part II | 1, 2, 3, 4