REQUESTED TESTIMONY ON MARYLAND STATE
HOUSE BILL-481 AND SENATE BILL S-472,
HUMAN CLONING PROHIBITION ACT OF 2004
Lowe House Office Building Room 161
Committee number 410-841-3770
Re: Human Cloning Bills
I appreciate very much the opportunity to submit my scientific testimony concerning Senate Bill S-472 (House version, H-481), "Human Cloning Prohibition Act of 2004. Please note that the scientific references given in the endnotes are in concert with the scientific experts in the field -- The International Nomina Embryologica Committee, which professionally requires specific scientific definitions for use in human embryology and related subjects.
As will be clear from my comments below, it is my sincere professional opinion that this Bill would require drastic measures by way of amendments and revisions before it could possibly serve the State of Maryland in the manner in which it proposes - i.e., as a Bill to prohibit human cloning. This concern is demonstrated, and documented, below as follows: http://mlis.state.md.us/2004rs/billfile/SB0472.htm
(B) "Human cloning" means human asexual reproduction accomplished by introducing the nuclear material of one or more human somatic cells into a fertilized or unfertilized oocyte who nucleus has been or will be removed or inactivated to produce a living organism at any stage of development with a human or predominantly human genetic constitution.
1. "human asexual reproduction": Note that this term, if accurately defined, should apply to all kinds of human cloning techniques, not just to the SCNT cloning technique (see #3, below). Note too that the cell(s), or even subcellular materials, used to initiate "human asexual reproduction" could be derived from a normal sexually reproduced IVF human embryo, from a previously cloned (asexually reproduced) human embryo, from human/non-human chimeras, or from genetic materials that are artificially constructed de novo.1 All of these kinds of cloning techniques, including the use of such human genetic materials, would be allowed by the Bill - for both "therapeutic" and "reproductive" purposes.
2. "by introducing the nuclear material": This refers to genetic material (DNA) found only inside the nucleus of the cell - and only that from a somatic cell. And because the Bill misdefines "genetic constitution" (see #8 below), it would even allow for the use of the real SCNT human cloning technique to clone human beings. Therefore, the Bill would allow the use of nuclear material found in both non-somatic (germ line) cells, as well as in somatic cells, as well as the use of human genetic materials (DNA) found outside the nucleus in the cytoplasm of any human cell for human cloning purposes (e.g., those found in mitochondria) - for both "therapeutic" and for "reproductive" purposes.
3. "of a human somatic cell": The Bill is defining "cloning" ONLY in terms of the somatic cell nuclear transplant (SCNT) cloning technique. However, there are many different kinds of human cloning techniques possible,2 e.g., twinning (blastomere separation and blastocyst splitting)3 -- a cloning technique highly promoted these days by IVF clinics for their patients.4 Needless to say, these same clinics could also perform twinning for the purpose of providing an unlimited supply of new human embryos for research purposes only. One can clone human beings by using such cloning techniques as somatic cell nuclear transfer (SCNT),5 germ line cell nuclear transfer (GLCNT),6 pronuclei transfer,7 and "artificially constructed" sperm, oocytes and embryos,8 etc.
Therefore this bill would allow the cloning of human beings by means of many different kinds of cloning techniques, for both "therapeutic" and "reproductive" purposes, e.g.: germ line cell nuclear transfer (GLSNT); "twinning" (blastomere separation and blastocyst splitting); pronuclei transfer; mitochondria transfer; embryos cloned by means of artificially constructed sperm and/or oocytes; parthenogenesis; production of human/human chimeras and human/non-human chimeras, etc.
4. "into a fertilized ... oocyte": A "fertilized oocyte" is already a new human embryo - a single-cell human zygote, a living human being. Therefore the Bill would allow the cloning of a new human embryo by using an already existing human embryo who would be profoundly genetically damaged or killed in the process.
5. "to produce a living organism ... with a human or predominantly human genetic constitution": Since not all kinds of human cloning techniques are prohibited by this bill, it would allow for the cloning of living organisms, with a human or predominantly human genetic constitution, to be performed - for both "therapeutic" and for "reproductive" purposes. Also, since this Bill misdefines "human genetic constitution", even the use of the SCNT human cloning technique could be used to produce living organisms with a human or predominantly human genetic constitution - for both "therapeutic" and for "reproductive" purposes.
(C) "Human somatic cell" means a diploid cell obtained or derived from a living or deceased human body at any stage of development.
6. "Human somatic cell," a diploid cell, having a complete set of chromosomes": By defining only a "somatic cell" as "a diploid cell", it blurs any distinction between diploid somatic cells and diploid germ line cells. There are two basic categories (or subsets) of diploid cells in the human organism, BOTH of which have a complete set of chromosomes - somatic cells and germ line cells.9 Since both kinds of cells are diploid, both kinds of cells can be used to clone human embryos using the nuclear transfer cloning technique. The Bill does not refer specifically to the use of diploid germ line cells. Therefore it would allow the cloning of human embryos by means of the germ line cell nuclear transfer (GLCNT) technique for both "therapeutic" and "reproductive" purposes. Additionally, since primitive germ line cells are also totipotent,10 the Bill would allow the cloning of human embryos by means of the "twinning" cloning technique for both "therapeutic" and "reproductive" purposes.
(D) "Nuclear transplantation" means transferring the nucleus of a human somatic cell into an oocyte from which the nucleus or all chromosomes have been or will be removed or rendered inert.
7. "'Nuclear transplantation,' transferring the nucleus of a human somatic cell": Both somatic cells and germ line cells have diploid nuclei - both of which nuclei can be transferred for cloning purposes. Therefore, the term "nuclear transplantation" would actually apply to both somatic and germ line cells. Here, only the nuclei of human somatic cells are referred to. Hence, human cloning by means of germ line cell nuclear transfer (as in the work of, e.g., cloning researcher John Gearhart) would not be prohibited - for both "therapeutic" or for "reproductive" purposes.
(E) "Nucleus" means the cell structure that houses the chromosomes.
8. "'Nucleus' means the cell structure that houses the chromosomes": The human genome is scientifically defined as including both nuclear chromosomes and those chromosomes that exist outside the nucleus (e.g., mitochondrial chromosomes). Therefore, the "nucleus" is not the only cell structure that houses human chromosomes; and thus, human genes exist outside, as well as inside, the nucleus. Therefore, this bill would not prohibit human cloning by means of mitochondrial DNA (chromosomes, genes) transfer (which genetically changes the genome of the resulting human embryo).
(F) "Oocyte" means the female germ cell or egg.
9. "the female germ cell, the egg.": It is because of the use of such (purposefully) sloppy scientific terms that so much (purposeful) confusion surrounds these and related issues. No effort is made to distinguish among the diploid totipotent primitive oocyte, the diploid primary oocyte, the diploid secondary oocyte, and the haploid female chromosomes formed in the new single-cell organism at the beginning of fertilization. Because the primitive oocyte is totipotent it could be cloned by "twinning"; because it is diploid it could be cloned by nuclear transfer - for both "therapeutic" and for "reproductive" purposes. Because the primary and secondary oocytes are diploid they could be cloned by nuclear transfer - for both "therapeutic" and for "reproductive" purposes. Although the bill appears to prohibit the transfer of a somatic cell nucleus into a "fertilized oocyte" - i.e., a new living embryo - it would not prohibit any other nuclear transfer cloning techniques, e.g., the transfer of a diploid germ line cell nucleus into a "fertilzed oocyte" (an embryo) - for "therapeutic" or "reproductive" purposes.
Ronan O'Rahilly, one of the originators of The Carnegie Stages of Early Human Embryological Development, and has sat on the international Nomina Embryologica Committee for decades, amusingly thus rejects the use of the term "egg": "Egg"; best confined to the hen and to cuisine; use "oocyte". [Ronan O'Rahilly and Fabiola Muller, Human Embryology & Teratology (New York: Wiley-Liss, 2001); p. 12]
10. Because of the erroneous scientific definitions and loopholes identified above, this Bill would not prevent a person from performing, attempting to perform, participating in, human cloning; nor would it prevent a person from transferring or receiving products of human cloning; nor from transferring or receiving, in whole or in part, any oocyte, embryo, fetus or somatic cell - or germ line cell - for the purpose of human cloning - for both therapeutic and reproductive human cloning.
(B.1) This subtitle may not be construed to prevent a person from conducting or attempting to conduct scientific research not specifically prohibited by this subtitle.
11. Precisely because this clause states that any research not specifically prohibited by this subtitle is not covered by this Bill, all human cloning techniques will not be prohibited by this Bill because of the erroneous science used in the above definitions relating to the somatic cell nuclear technique (SCNT) - thus failing to define the real SCNT human cloning technique -- and because all of the many other types of human cloning techniques are not specifically mentioned.
(B.2) A person may not conduct or attempt to conduct scientific research that uses nuclear transfer or other cloning techniques to produce:
12. Section 3 is a typical legal "restriction" clause, essentially stating that anything NOT specified as prohibited in this Bill is not covered by this Bill (i.e., it is therefore legally allowed). Some specific actions are usually listed, as above. However, this "restriction" clause itself would allow for extensive human cloning, using many different human cloning techniques - for both "therapeutic" and for "reproductive" purposes, e.g.:
A. "molecules, deoxyribonucleic acid": Some cloning of human embryos is accomplished by means of pronuclei transfer. For example, the male pronucleus from the just-fertilized oocyte of one human embryo, and the female pronucleus from the just-fertilized oocyte of another human embryo can be removed by micromanipulation and placed together in an enucleated oocyte, which is then stimulated, and a new cloned human embryo would be reproduced. In fact, such embryos would be human/human chimeras. Human pronuclei are not whole cells, nor whole nuclei, but only parts of nuclei - just molecules, and they are molecules of DNA. Therefore the prohibition in the Bill would allow the cloning of human embryos by means of pronuclei transfer for both "therapeutic" and "reproductive" purposes. The same problem exists with the use of artificially constructed sperm, oocytes and/or embryos.
B. "cells other than human embryos": would not cover the cloning of a single cell -- such as the single-cell human zygote - using all cloning techniques for both "therapeutic" and "reproductive" purposes. Nor would it cover -- depending on when during the fertilization process a new human being begins to exist -- the use of pronuclei transfer for both "therapeutic" and "reproductive" purposes, since pronuclei are only parts of a single cell.
C. "tissues": many researchers use the phrase "human tissues" to refer to what are in reality totipotent diploid human primordial germ line cells. Thus the cloning of new human beings by means of twinning these totipotent cells, or cloning them by means of nuclear transfer, for both "therapeutic" and "reproductive" purposes, would not be covered if the researchers' deceptive definition of "tissues" is accepted.
Respectfully submitted,
Dr. Dianne N. Irving, M.A., Ph.D.
1 Such are the stated goals of "nano/bio/info/cogno", supported by this government and many internationally popular "futuristic" programs, e.g., see Converging Technologies for Improving Human Performance (National Science Foundation, and the U.S. Dept. of Commerce, June 2002); you can find the report at: http://itri.loyola.edu/ConvergingTechnologies/Report/NBIC pre publication.pdf (or at http://www.wtec.org/reports.htm). Also, the term "reprogenetics" is coined for such research in a recent "Special Supplement" of The Hastings Center Report (July/August 2003) at (http://www.thehastingscenter.org/news/features/repro%20supplement.pdf), the first sentence of which refers to reprogenetics as "one big embryo experiment". The term refers collectively to the converging of several scientific technologies, especially multiple artificial human reproductive techniques (e.g., IVF and cloning) and human genetics research - other wise known as eugenics. The term is similar to such others as "trans-humanism", "post-humanism", "futurism", etc. - i.e., the remaking of human nature by the use of experimental reproductive and genetic techniques. [Back]
2 National Institutes of Health, Office of Science Planning and Policy, "CLONING: Present Uses and Promises", April 27, 1998), at: http://www1.od.nih.gov/osp/ospp/scipol/cloning.htm: "Cloning and somatic cell nuclear transfer are not synonymous. Cloning is the production of a precise genetic copy of DNA, a cell, or an individual plant or animal. Cloning can be successfully accomplished by using a number of different technologies. Somatic cell nuclear transfer is one specific technology that can be used for cloning." See also: Australia, The Cloning of Humans (Prevention) Bill 2001 (Queensland): "Cloning can occur naturally in the asexual reproduction of plants, the formation of identical twins and the multiplication of cells in the natural process of repair. The cloning of DNA, cells, tissues, organs and whole individuals is also achievable with artificial technologies. ... The cloning of a cell or an individual may be achieved through a number of techniques, including: molecular cloning ..., blastomere separation (sometimes called "twinning" after the naturally occurring process that creates identical twins): splitting a developing embryo soon after fertilisation of the egg by a sperm (sexual reproduction) to give rise to two or more embryos. The resulting organisms are identical twins (clones) containing DNA from both the mother and the father. ... somatic cell nuclear transfer: the transfer of the nucleus of a somatic cell into an unfertilised egg whose nucleus, and thus its genetic material, has been removed. A number of scientific review bodies have noted that the term "cloning" is applicable in various contexts, as a result of the development of a range of cloning techniques with varying applications", at: http://www.parliament.qld.gov.au/Parlib/Publications_pdfs/books/2001036.pdf. [Back]
3 Strachan and Read, 1999: "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." (p. 508) [Back]
4 Many IVF providers are strongly promoting the use of twinning cloning techniques, a process they refer to as "embryo multiplication", e.g.: "Because early embryonic cells are totipotent, the possibility of splitting or separating the blastomeres of early preimplantation embryos to increase the number of embryos that are available for IVF treatment of infertility is being discussed Because embryo splitting could lead to two or more embryos with the same genome, the term "cloning" has been used to describe this practice. ... Whereas these ethical concerns raise important issues, neither alone nor together do they offer sufficient reasons for not proceeding with research into embryo splitting and blastomere separation. ... In sum, since embryo splitting has the potential to improve the efficacy of IVF treatments for infertility, research to investigate the technique is ethically acceptable. Persons asked to donate gametes or embryos for such research should be fully informed that research in embryo splitting is intended or planned as a result of their donation. The fears of possible future abuses of the technique are not sufficient to stop valid research in use of embryo splitting as a treatment for infertility. This statement was developed by the American Society for Reproductive Medicine's Ethics Committee and accepted by the Board of Directors on December 8, 1995." See, AMERICAN SOCIETY OF REPRODUCTIVE MEDICINE, at: http://www.asrm.com/Media/Ethics/embsplit.html.
See also: "New Ways to Produce Identical Twins -- A Continuing Controversy": "Now, a new method of actually producing identical twins looms near. Called "blastomere separation" (the separation of a two- to eight-cell blastomere into two identical demi-embryos), it is potentially one method of helping infertile couples have children through in vitro fertilization (IVF). ... The following is excerpted from the medical journal Assisted Reproduction Reviews, May 1994. Dr. Joe B. Massey, who heads an in vitro clinic in Atlanta. Dr. Massey reviews the advances in blastomere separation and discusses the potential indications, benefits, limitations, and ethics of using this method to produce monozygotic twin embryos for IVF patients. The Twins Foundation, by presenting Dr. Massey's material for your information neither advocates nor rejects any such procedures: 'Embryo Multiplication by Blastomere Separation -- One Doctor's Proposal'. [Massey]: In spite of many advances in human in vitro fertilization (IVF), there are still many problems. ... According to Dr. Massey, 'Observations on the potential impact of removing less than half of the cells from the human embryo have been well documented in pre-clinical embryo biopsy studies.' (For more on this story see Research Update Vol. 9, No. 1, 1994)." See, THE TWINS FOUNDATION, at: http://twinsfoundation.com/ru-v9n1-1994.htm.
See also: Professor Dr. Mithhat Erenus, "Embryo Multiplication": "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 [twinning by "blastomere splitting"]. .... 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.." at: http://www.hekim.net/~erenus/20002001/asistedreproduction/micromanipulation/embryo_multiplication.htm.
See also "embryo self-selection": "The ability to grow embryos for five days to the blastocyst stage of development in the laboratory, rather than the traditional three days, allows clinicians to determine with greater certainty which embryos are really the "best" in terms of their potential for implantation. Consequently, blastocyst culture makes it possible to select the best one or two blastocysts vs. three or four early embryos to transfer back to the mother. Fertility centers like Shady Grove constantly strive to improve IVF success rates through the steady refinements of clinical and laboratory techniques. Clinical blastocyst culture and transfer is the next important step in that evolution,' explains Robert Stillman, MD: 'After five days of growth, the cells of the embryo should have divided many times over, and have begun to differentiate by function. The embryos that survive to this stage of development are usually strong, healthy, and robust. ... Simply put, this self selection can be viewed as 'survival of the fittest. ... Which ones to transfer? Which ones are really the "best'? Two additional days in the blastocyst culture medium allows the natural winnowing process to continue. Thus, after 5 days of growth in the laboratory, only 2 or 3 of the original ten embryos may remain viable. We now know the best embryos to transfer. ... In thinking of the example above, patients who have fewer oocytes retrieved, fewer fertilized or fewer dividing embryos by day three in culture have no advantage using blastocyst culture, since little is to be gained in further embryo 'self selection'. Dr. Stillman emphasizes."
FERTILITY NETWORK, at: http://fertilitynetwork.com/articles/articles-blastocyst.htm.
Also, ETHICS COMMITTEE OF THE AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE, "'Ethical Considerations of Assisted Reproductive Technologies': Originally published as a supplement to the ASRM medical journal (Fertility and Sterility 1994;62:Suppl 1), Ethical Considerations for Assisted Reproductive Technologies covers the American Society for Reproductive Medicine's position on several aspects of reproductive medicine, including: ... the moral and legal status of the preembryo, ... the use of donor sperm, donor oocytes and donor preembryos, ... the cryopreservation of oocytes and preembryos, micro techniques such as: zona drilling, microinjection, blastomere separation (cloning), and assisted hatching." at: http://www.asrm.com/Media/Ethics/ethics94.html. [Back]
5 Strachan and Read, 1999: "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." (pp. 508-509). [Back]
6 Larsen, 1998: "Like all normal somatic (i.e., non-germ cells), the primordial germ cells contain 23 pairs of chromosomes, or a total of 46 [and thus could be cloned by nuclear transplant]" (p. 4); Strachan and Read, 1999: "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. (p. 28); Moore and Persaud 1998: "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)." (p. 18); Carlson, 1999: "In a mitotic division, each germ cell produces two diploid progeny that are genetically equal." (p. 2); O'Rahilly and Muller, 2001: "Future somatic cells thereby lose their totipotency and are liable to senescence, whereas germ cells regain their totipotency after meiosis and fertilization [and therefore could undergo regulation to produce new embryos]." (p. 39); Strachan and Read, 1999: "Early primordial germ cells are spared; their genomic DNA remains very largely unmethylated until after gonadal differentiation and as the germ cells develop whereupon widespread de novo methylation occurs. (p. 191) [Back]
7 See, e.g., Philip Cohen, "Like a virgin", in Cloning: Special Report, at: http://iggi.unesco.or.kr/web/iggi_docs/04/952655279.pdf; Gordon, J.W. and Ruddle, F.H. (1981) "Integration and stable germline transmission of genes injected into mouse pronuclei," Science 214: 1244-1246; M. C. Valiotis, O. Lacham-Kaplan and A. O. Trounson, "Pronuclei formation and embryo cleavage following electrofusion of round spermatids with oocytes from the mouse", Australian Society for Reproductive Biology, p. 48, 1993. [Back]
8 See, for example, the current New Zealand cloning bill, which defines a "gamete" as including "any other cell (whether naturally occurring or artificially formed or modified) that contains only 1 copy of all or most chromosomes; and is capable of being used for reproductive purposes." [ Human Assisted Reproductive Technology Bill: Supplementary Order Paper [HART SOP], April 2003, at http://www.justice.govt.nz/pubs/other/pamphlets/2003/hart/Supp_order_paper.pdf. To grasp the entirety of what this legislation would embrace, see the government's on-line pamphlet, Governmental Proposals to Amend the Human Assisted Reproductive Technology Bill: Questions and Answers [Q&A], May 2003, at: http://www.justice.govt.nz/justicepubs/other/pamphlets/2003/hart/questions.html.] The term "reprogenetics" is coined for such "artificially constructed" materials in a recent "Special Supplement" of The Hastings Center Report (July/August 2003) at (http://www.thehastingscenter.org/news/features/repro%20supplement.pdf), the first sentence of which refers to reprogenetics as "one big embryo experiment". The term refers collectively to the converging of several scientific technologies, especially multiple artificial human reproductive techniques and human genetics research - other wise known as eugenics. The term is similar to such others as "transhumanism", "post humanism", "futurism", etc. - i.e., the remaking of human nature by the use of experimental reproductive and genetic techniques. Such are the stated goals of "nano/bio/info/cogno", supported by this government and many internationally popular "futuristic" programs, e.g., see Converging Technologies for Improving Human Performance (National Science Foundation, and the U.S. Dept. of Commerce, June 2002); you can find the report at: http://itri.loyola.edu/ConvergingTechnologies/Report/NBIC prepublication.pdf (or at http://www.wtec.org/reports.htm). [Back]
9 O'Rahilly and Muller, 2001: "Gametogenesis is the production of germ cells (gametes), i.e., spermatozoa and oocytes. ... 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. ... Diploid refers to the presence of two sets of homologous chromosomes: 23 pairs, making a total of 46. This is characteristic of somatic and primordial germ cells alike." (p. 19); Strachan and Read (1999): "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 ... ." (p. 28); Moore and Persaud, 1998: " 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)." (p. 18); Carlson, 1999: "In a mitotic division, each germ cell produces two diploid progeny that are genetically equal." (p. 2); Larsen , 1998: "Like all normal somatic cells (i.e., non-germ cells), the primordial germ cells contain 23 pairs of chromosomes, or a total of 46." (p. 4) [Back]
10 O'Rahilly and Muller, 2001: "[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 1/2 weeks and possibly much earlier. ... The unifying feature in the formation of primordial germ cells would seem to be the exemption of those cells from the processes of regional, somatic differentiation. (pp., 23-24) ... Cells differentiate by the switching off of large portions of their genome. Future somatic cells thereby lose their totipotency and are liable to senescence, whereas germ cells regain their totipotency after meiosis and fertilization. (p. 39) ... Stem cells comprise a small subpopulation of multipotent or pluripotent, ultrastructurally unspecialized, slow-cycling cells that possess the ability of self-renewal and can produce cells that are destined to differentiate. (In contrast, primordial germ cells and those of a morula are totipotent; i.e., they can develop into any type of embryonic tissue and can even form an entirely new embryo)." (p. 136) [Back]