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

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[B.] Research Using “Human Fetal Stem Cells”

Among the “pluripotent stem cells” identified in the NIH Guidelines are what they refer to as “fetal tissue stem cells.” The use of such “fetal tissue stem cells” in research, the NIH Guidelines state, is already legal because such research falls under the Federal statutory restrictions regulations regarding fetal tissue research [42 U.S.C. § 289g-2(a); Federal regulations at 45 CFR § 46.210; 42. U.S.C. § 289g-1 and 42. U.S.C. § 289g-2(b)]. But are “fetal tissue stem cells” just some vague blob of “fetal tissue”—like, for instance, the kind used in the celebrated Parkinson's research we've all heard so much about? Not quite.

[1.] What “fetal stem cells” really are:

“Fetal stem cells” are the primitive sex cells, the “germ line” cells, which when they finally mature decades later can take part in fertilization as sperms and secondary oocytes to produce new human beings/embryos.

These primitive sex cells begin to develop very early in the developing human embryo—some human embryologists claim as early as the blastocyst stage (emphases added):

“Gametogenesis is the production of germ cells (gametes), i.e., spermatozoa and oocytes. These cells are produced in the gonads, i.e., the testes and ovaries respectively. The gametes are believed to arise by successive divisions from a distinct line of cells (the germ plasm), and the cells that are not directly concerned with gametogenesis are termed somatic.…The reduction of chromosomal number from 46 (the diploid number) to 23 (the haploid number) is accomplished by a cellular division termed meiosis.…Primordial germ cells…are difficult to recognize in very young human embryos. Claims for them have been made as early as in the blastocyst, and they are believed to be segregated at latest by 2 weeks and possibly much earlier.” [O'Rahilly and Muller (1994), pp. 13-14]

In addition, these “fetal stem cells” are usually removed from early developing aborted human embryos, not from fetuses (the embryonic period begins at fertilization and extends to the end of 8 weeks; the fetal period begins at 9 weeks and continues until birth). One wonders, then, why they are referred to as “fetal stem cells,” rather than as “embryonic stem cells”? Could it be in order to “qualify” them as “fetal tissue,” the use of which in “fetal tissue transplant research” is already legally valid in our federal statutes and regulations?

These “fetal stem cells” are also not somatic cells (which are defined as all the cells of the body with the exception of the germ-line cells). Nor are germ-line cells in the haploid state. They are diploid (contain the full complement of human DNA) during the decades of years required to mature them, the significance being that because they are still diploid they too may be cloned, just as somatic cells may be cloned, by any of several cloning techniques. These primitive sex cells—both male and female—may also be matured and then used in IVF or other reproductive methods to produce new living human embryos (emphases added):

“A subset of the diploid body cells constitute the germ line. These give rise to specialized diploid cells in the ovary and testis that can divide by meiosis to produce haploid gametes (sperm and egg).…The other cells of the body, apart from the germ line, are known as somatic cells…most somatic cells are diploid …” [Tom Strachan and Andrew Read, Human Molecular Genetics: Second Edition (New York: Wiley-Liss, 1999), p. 28]

“Meiosis is a special type of cell division that involves two meiotic cell divisions; it takes place in germ cells only. Diploid germ cells give rise to haploid gametes (sperms and oocytes).” [Moore and Persaud (1998), p. 18]

“In a mitotic division, each germ cell produces two diploid progeny that are genetically equal.” [Carlson (1999), p. 2]

“Like all normal somatic (i.e., non-germ cells), the primordial germ cells contain 23 pairs of chromosomes, or a total of 46.” [Larsen, (1998), p. 4]

Of significance too is that these germ-line cells are the cells used for “positive” eugenic purposes (emphases added):

There are serious concerns, therefore, that a hidden motive for germline gene therapy is to enable research to be done on germline manipulation with the ultimate aim of germline-based genetic enhancement. The latter could result in positive eugenics programs, whereby planned genetic modification of the germline could involve artificial selection for genes that are thought to confer advantageous traits.” [Tom Strachan and Andrew Read, Human Molecular Genetics: Second Edition (New York: Wiley-Liss, 1999), pp. 539-541]

(See other discussions of human germ line “therapy” using DNA-recombinant human gene germ line “transfer” in: Carlson (1999), pp. 46-47; Larsen (1997), pp. 22-28; Benjamin Lewin (ed.), Genes III (New York: John Wiley & Sons, 1987), pp. 353-354.]

That is, these human germ-line cells, both male and female, can be injected with new foreign genes (human or animal, forming “chimeras"), and cloned to produced new living human embryos. Or they can be matured to the haploid state, and subsequently used in fertilization to produce new human beings/embryos. In either case, all of the cells of these new human embryos are therefore also permanently genetically changed—including their primitive sex cells. Thus, when these human beings grow up and later take part in reproduction—sexual or asexual—all subsequent new human beings or progeny will carry the new foreign genes as well, and perpetuate those genetic changes down through the generations. The genetic changes may be for “curing diseases,” for “genetic enhancements only,” or for “the advancement of scientific knowledge.” It is worth repeating that human germ line gene transfer is a distinctive form of human cloning by means of genetic transfer of identical “copies” of human or animal genetic materials, using asexual and then sexual reproduction through the generations. The “foreign” genetic materials are transferred by using cloning vectors (emphases added):

Clone describes a large number of cells or molecules identical with a single ancestral cell or molecule.” (p. 955)… [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)]

“The term ‘clones’ indicates genetic identity and so can describe genetically identical molecules (DNA clones), genetically identical cells or genetically identical organisms.” [Tom Strachan and Andrew P. Read, Human Molecular Genetics 2 (New York: John Wiley & Sons, Inc, 1999), pp. 508-509]

It is also of peculiar interest that some of these “fetal stem cells” would seem to be capable of being totipotent—at least if derived from the early human embryo—IVF-produced or culture-produced—from the blastocyst stage until the “formation of the mesoderm,” as already scientifically documented in this analysis. As with “human embryonic stem cells,” these “fetal stem cells” derived from the early human embryo could also revert to being new human embryos due to regulation. If this research were performed,this would constitute human embryo research, which would violate the Congressional ban.It would also violate the NIH Guidelines themselves.

Germ-line cells, aka “fetal stem cells,” could also apparently be derived from IVF-produced or culture produced human embryos from the blastocyst stage until before the “formation of the mesoderm,” and then cloned, producing new living human embryos, since they would still be diploid. Or, they could be allowed to mature to the haploid state, and then used in fertilization to produce new living human embryos. The production of living human embryos, by both cloning or by fertilization, would constitute human embryo research per se, and would violate the existing Congressional ban.

Nor, it would seem, would the use of most of these cells, by definition, accurately fall under protection of the various human fetal tissue transplant statutes and regulations as claimed in these NIH Guidelines, because they are mostly derived from embryos, not from fetuses, and therefore they would not be derived from “fetal tissue”; they would be derived from “embryonic tissue.” Nor could such research be justified by referring to our federal OPRR regulations for the use of human subjects in research. Those federal regulations quite erroneously define the “fetus” as beginning at implantation (5-7 days post fertilization). However, the accurate scientific definition of “fetus” is the developing human being from the 9th week post-fertilization until birth. Therefore any tissue retrieved before 9 weeks would be embryonic tissue, not fetal tissue. Besides, these IVF-produced and culture-produced human embryos would not be implanted yet.

Thus, human “fetal stem cells” are really mostly human “embryonic stem cells,” and their use, it seems, should not properly fall under the federal statutes and regulations dealing with “fetal tissue transplant research.” Furthermore, to use the immature human germ line cells for cloning to produce human embryos, to mature and use these “fetal stem cells” in fertilization to produce living human embryos, or to derive them from IVF-produced or culture-produced human embryos for similar purposes, would surely constitute “human embryo research” per se, and therefore would violate the Congressional ban, as well as be prohibited by the NIH Guidelines themselves.

[2.] Submissions by investigators:

For research that is eligible for NIH funding, the NIH Guidelines require an assurance from intramural and extramural investigators who are intending to use existing NIH funds that “the pluripotent stem cells were derived from human fetal tissue in accordance with the conditions set forth in Section II.B.2 of these Guidelines” (which refers to the existing federal regulations and statutes pertaining to “fetal tissue transplant research”) (p. 10). However, since these “fetal stem cells” are mostly “embryonic stem cells,” it would seem that they could not fall under the protection of these federal regulations and statutes, because most of them are not derived from “fetuses.” If they do, then perhaps those federal regulations and statutes are in need of serious reconsideration and revision.

Also, because some of these “fetal stem cells”—whether derived from frozen IVF human embryos or from culture-produced human embryos—could be “totipotent” rather than “pluripotent.” Thus it is difficult to understand how such research using “pluripotent” stem cells could be “eligible” for NIH finding.

Once again, do investigators know the correct scientific facts of human embryology and human molecular genetics required to submit a scientifically credible assurance to the NIH? Do members serving on the institutional Review Boards (IRB‚s) have the required scientific knowledge to evaluate and approve such “fetal stem cell research.” How does NIH assure that?

[3.] Informed consent:

As noted in the previous discussion concerning “human embryonic stem cells,” the purpose of “informed consent” is to provide a decision maker with the information necessary to make an “informed” decision based on knowledge of the accurate facts involved, as well as to assure that no pressures have been forced on this person's will that would cause him/her to make a decision that was unintended or undesired. Most of the concerns for ethically and legally valid informed consent already mentioned with respect to the use of “human embryonic stem cells” apply to the use of “fetal stem cells” as well.

But in addition to those concerns, one wonders if the donors of “fetal tissue,” from which these “fetal stem cells” are derived, are informed that this tissue also consists of the primitive sex cells, the germ line cells? Do they realize that these “fetal tissues” are mostly derived from their embryos, not from their fetuses, and therefore might not be protected by the federal regulations and statutes on “fetal tissue transplant research,” or by the OPRR regulations? Are they told that these germ line cells may be totipotent, and therefore could form new living human embryos themselves, with derivable totipotent “stem cells” themselves? Are they informed that their “fetal stem cells” could be cloned to produce new living human embryos, matured and then fertilized to produce new living human embryos, or used in DNA-recombinant human gene germ line research and “therapy” for both “positive” and “negative” eugenic purposes, creating new living human beings with foreign genetic changes from their progeny, and from their progeny, down through the generations? Are the donors of frozen IVF-produced human embryos informed that their embryos, from the blastocyst stage until before the formation of the mesoderm, might also contain these primitive sex cells, or germ line cells? And that these germ line cells could be used in all of the same kinds of research as are “fetal stem cells”? Would these donors not care, or not want to know this critical scientific information, and if not, is that really ethically and legally valid informed consent?

And once again, who is ethically and legally responsible for any “uninformed consents”?

[4.] Oversight:

Finally, in addition to the IRB's that NIH relies on to evaluate and approve the submissions and assurances from investigators for this research, the NIH Guidelines state that the “NIH Human Pluripotent Stem Cell Review Group (HPSCRG) will review documentation of compliance with the Guidelines for funding requests that propose the use of human pluripotent stem cells” (p. 12), and that a Scientific Review Group will review “cases of new or competing (renewal) or competing supplement applications” (p. 13). The obvious but very valid question is whether the members of this HPSCRG or the Review Group themselves know the required established facts of human embryology and human molecular genetics to be able to competently review documentation of compliance with the Guidelines, or to review new applications.

Far too many unanswered questions remain concerning “human pluripotent stem cell research"—both scientific and ethical. Perhaps the decision to allow such research, and to fund it—privately or publicly—would be premature.

[Part III will follow, consisting in the application of the correct science to the recent NIH stem cell report, the informed consent and safety of human patients who would participate in the use of human “pluripotent” stem cell “therapy” in clinical trials, and a summary of the entire analysis.]

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