What Human Embryo?
Funniest Mental Gymnastics from Medicine and Research


1 Much of this presentation is drawn from my recent article, "Analysis of Legislative and Regulatory Chaos in the U.S.: Asexual Human Reproduction and Genetic Engineering" (October 4, 2004), in press; presented to Guild of St. Luke, White Mass, Archdiocese of Boston, Boston, MA, Oct. 14, 2004. [Back]

2  The Carnegie Stages of Early Human Development is the basis for the Nomina Embryologica which was part of the larger Nomina Anatomica for decades until 1989. In 1999 the name was changed by the International Associations of Anatomists to Terminologia Embryologica and Terminologia Anatomica, which was published in 1999 by the IFAA and is available for sale in book or CD-Rom format at: http://www.thieme.com/SID2194056226451/productsubpages/pubid-1163116455.html. For on-line access to information about the international Nomina Embryologica Committee and the Carnegie Stages of Early Human Development, see U.S. national website at the National Museum of Health and Medicine, Armed Forces Institute of Pathology: http://nmhm.washingtondc.museum/, Human Developmental Anatomy Center; http://nmhm.washingtondc.museum/collections/hdac/index.htm, the Carnegie Collection of Embryology; http://nmhm.washingtondc.museum/collections/hdac/Carnegie_collection.htm.

The scientific quotes on human embryology herein are taken directly from the following internationally recognized human embryology textbooks in concert with the Carnegie Stages and the international nomenclature on human embryology: Ronan O'Rahilly and Fabiola Muller, Human Embryology & Teratology (New York: Wiley-Liss, 2001): In preparing this book, the authors have made full use of the [Carnegie Embryological] Collection and of the various published studies, whether by themselves or by others, based on what George W. Corner felicitously termed that "Bureau of Standards." ... Serious work in human embryology now depends on staging and the internationally accepted system of Carnegie embryonic stages (a term introduced by the senior author) has been adopted throughout. ... A scheme of embryonic stages can be found on the inside front cover of this book. These developmental stages are indicated by superscripts throughout this book, thereby avoiding interruptions in the flow of the text. (p. ix)

Ibid, O'Rahilly and Muller (1994): Wilhelm His, Senior (1831-1904), the founder of human embryology [Fig. 1-1]. ... [H]uman embryology is scarcely more than one hundred years old. The first to study the human embryo systematically was Wilhelm His, Senior, who established the basis of reconstruction, i.e., the assembling of three-dimensional form from microscopic sections. His, who has been called the "Vesalium of human embryology," published his three-volume masterpiece Anatomie menschlicher Embryonen in 1880-85 [His, Vogel, Leipzig]. In it the human embryo was studied as a whole for the first time. ... A detailed Handbook of Human Embryology by Keibel and Mall appeared in 1910-12. Franklin P. Mall, who studied under His, established the Carnegie Embryological Collection in Baltimore and was the first person to stage human embryos (in 1914). Mall's collection soon became the most important repository of human embryos in the world and has ever since served as a "Bureau of Standards". Mall's successor, George L. Streeter, laid down the basis of the currently used staging system for human embryos (1942-48), which was completed by O'Rahilly (1973) and revised by O'Rahilly and Muller (1987). (p. 3)

Keith Moore and T. V. N. Persaud, The Developing Human: Clinically Oriented Embryology (6th ed. only) (Philadelphia: W.B. Saunders Company, 1998): Schleiden and Schwann were responsible for great advances being made in embryology when they formulated the cell theory in 1839. This concept stated that the body is composed of cells and cell products. The cell theory soon led to the realization that the embryo developed from a single cell, the zygote, which underwent many cell divisions as the tissues and organs formed. (p. 12)

For more historical information on the development of these international standards, see, e.g., article on Wilhelm Hiss, at: http://www.whonamedit.com/doctor.cfm/2606.html [Back]

3  See, e.g., Cloning researcher, Geraedts JP, de Wert GM., "Cloning is possible by nucleus transplantation and by embryo splitting. Nucleus transplantation does not result in a genetically completely identical individual because the mitochondrial DNA originates from the ovum donor. Embryo splitting may be regarded as the artificial production of a monozygotic multiplet," in "Cloning: applications in humans; Technical aspects." [Ned Tijdschr Tandheelkd. 2001 Apr;108(4):145-50]; [PMID: 11383357], http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11383357.

Famed infertility expert, Peter R. Brinsden, "The Authority has considered the ethical and social implications of cloning by splitting embryos, since this is not covered by the Act, whereas cloning of human embryos by nuclear replacement is." ["Regulation of assisted reproductive technology: The UK experience", in Peter R. Brinsden (ed.), A Textbook of In Vitro Fertilization and Assisted Reproduction (2nd ed) (New York: The Parthenon Publishing Group, 1999)] [Bourn Hall Clinic, Cambridge, UK], p. 421.

British researcher, Dr Anne McLaren: "1.1 Cloning ... may involve division of a single embryo, in which case both the nuclear genes and the small number of mitochondrial genes would be identical, or it may involve nuclear transfer, in which case only the nuclear genes would be identical. ... 1.6 In contrast, cloning by embryo splitting, from the 2-cell up to the blastocyst stage, has been extensively used in sheep and cattle to increase the yield of progeny from genetically high-grade parents. [Opinion of the Group of Advisers on the Ethical Implications of Biotechnology to the European Commission, requested by the European Commission on 28 February 1997], http://europa.eu.int/comm/european_group_ethics/gaieb/en/opinion9.pdf.

Bioethics lawyer George Annas: "Twinning by splitting an extracorporeal human embryo in two is the most rudimentary form of human cloning, and the closest to natural twins." ["Human Cloning: A Choice or an Echo?; II. Cloning and Imagination", University of Dayton Law Review, Winter 1998, Vol. 23, Num. 2], http://www.bumc.bu.edu/www/sph/lw/pvl/html3-variant.html.

Lawyers, economists and ethicists Campbell et al: "Germ-line tinkering is the end to which these three lines of research that I mentioned earlier are headed. [Nuclear transplantation, genetic engineering, and reproductive medicine.] In 1983, when the first artificial twinning of horses was performed in this country using another type of cloning known as blastomere separation, [ftnt. 110] ethicists insisted that no one would ever attempt the procedure on humans because there was too much opposition within ethical review boards and other institutional oversight bodies to permit it. They were wrong. In 1993, Jerry Hall at George Washington University Medical Center performed blastomere separation using "genetically abnormal" human embryos. He told Science that he did it intentionally to "get the ethical discussion moving." The discussion did not "move", however, just as it did not move in the late 1960s, when scientists issued the same assurance that cloning of anything was impossible and unthinkable. We should have known better, but too often in our society, we react only to what exists. Now, we have the unthinkable and we must scramble to catch up. [ftnt. 110: In relation to cloning, blastomere separation "splits the cells or blastomeres of an early multicelled embryo before the cells have begun to differentiate. Because each blastomere at this stage is in theory totipotent (that is, capable of producing an entire organism itself), separated cells can become new embryos, all of which have the same genome." John A. Robertson, "The Question of Human Cloning", Hastings Center Report (Mar. 1, 1994), p. 6]. [P. Campbell, G. Maranto, C. R. Cantor, L. H. Glantz, and F. H. Miller, "Gene Therapy: Legal, Financial and Ethical Issues", Boston University Journal of Science and Technology Law, March 20, 1997, pp. 18-19 [http://www.bu.edu/law/scitech/volume4/4jstl03.pdf].

The Council of Europe: "The member States of the Council of Europe, the other States and the European Community Signatories to this Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, ... Noting scientific developments in the field of mammal cloning, particularly through embryo splitting and nuclear transfer ...". [Human Cloning Regulation in Europe, in American Center for Law and Justice, Info Letters, CFJD MEMO, 2001-03-09], http://www.aclj.org/cloning/cloning_cfjd_europe.asp.

National Institutes of Health, Office of Science Planning and Policy: "Cloning and somatic cell nuclear transfer are not synonymous. Cloning can be successfully accomplished by using a number of different technologies." [CLONING: Present Uses and Promises, April 27, 1998], http://www1.od.nih.gov/osp/ospp/scipol/cloning.htm. See also, NIH Guidelines for Research Using Human Pluipotent Stem Cells: "If these cells separate, genetically identical embryos result, the basis of identical twinning." (p. A-3)

Australia, The Cloning of Humans (Prevention) Bill 2001 (Queensland): "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.", http://www.parliament.qld.gov.au/Parlib/Publications_pdfs/books/2001036.pdf.

(in vitro) Human molecular geneticists, Strachan and Read: "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." [Human Molecular Genetics 2 (2nd ed.) (New York: John Wiley & Sons, Inc., 1999), pp. 508-509].

(in vivo) Human embryologists, O'Rahilly and Muller: "The embryo enters the uterine cavity after about half a week ... Each cell (blastomere) is considered to be still totipotent (capable, on isolation, of forming a complete embryo), and separation of these early cells is believed to account for one-third of cases of monozygotic twinning." [Human Embryology & Teratology (New York: Wiley-Liss, 2001, p. 37].

Human embryologist, Bruce Carlson: "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 determine 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, ... " (p. 44); " ... Some types of twinning represent a natural experiment that demonstrates the highly regulative nature of early human embryos, ..." (p. 48); "... 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." [Human Embryology and Developmental Biology (St. Louis, MO: Mosby, 1994); also, Carlson, ibid., (2nd ed., 1999), p. 49].

Human embryologist, William Larsen: "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." [Essentials of Human Embryology (New York: Churchill Livingstone, 1998), p. 325].

American Society of Reproductive Medicine: "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 abuses of the technique are not sufficient to stop valid research in use of embryo splitting as a treatment for infertility." (http://www.asrm.com/Media/Ethics/embsplit.html).

Ethics Committee of the American Society for Reproductive Medicine: "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, ... micro techniques such as: zona drilling, microinjection, blastomere separation (cloning), and assisted hatching." ("'Ethical Considerations of Assisted Reproductive Technologies': Originally published as a supplement to the ASRM medical journal [Fertility and Sterility 1994;62:Suppl 1], http://www.asrm.com/Media/Ethics/ethics94.html.

The Twins Foundation: "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)," in "New Ways to Produce Identical Twins -- A Continuing Controversy", http://twinsfoundation.com/ru-v9n1-1994.htm.

Dr. Mithhat Erenus: "In such cases, patients may benefit from embryo multiplication ... Since each early embryonic cell is totipotent (i.e., has the ability to develop and produce a normal adult), embryo multiplication is technically possible. ... 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." ("Embryo Multiplication", http://www.hekim.net/~erenus/20002001/asistedreproduction/micromanipulation/embryo_multiplication.htm, and at http://fertilitynetwork.com/articles/articles-blastocyst.htm). [Back]

4 For an extensive 31-page summary of selected bibliography of recent research studies on PubMed using such human materials for cloning and genetic engineering, see Irving, "Scientific References, Human Genetic Engineering (Including Cloning): Artificial Human Embryos, Oocytes, Sperms, Chromosomes and Genes" (May 25, 2004), at http://www.lifeissues.net/writers/irv/irv_25scientificrefer1.html. [Back]

5  For those who are still unaware, there are already National Institutes of Nanotechnology in over 40 different countries, including the United States. Such cloning, using "artificially constructed" chromosomes, sperms, oocytes, and embryos, is included in the current New Zealand bill on human artificial reproductive technologies (HART Bill): "gamete means ---- (a) an egg or a sperm, whether mature or not; or (b) any other cell (whether naturally occurring or artificially formed or modified) that --- (i) contains only 1 copy of all or most chromosomes; and (ii) is capable of being used for reproductive purposes." http://www.justice.govt.nz/pubs/other/pamphlets/2003/hart/Supp_order_paper.pdf.

The term "reprogenetics" is coined 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. 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). See also, 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.]

See also recent legal analysis of "nanocloning": [addendum 6-3-04] "Nanotechnology can be used to clone machines as well as living creatures. Issues similar to those currently plaguing policy makers about biological cloning need to be raised early in the life of nanotechnology. ... Proponents of nanotechnology postulate a world where DNA strands can be custom built by repairing or replacing sequences in existing strands of DNA or even by building the entire strand, from scratch, one sequence at a time. With enough nanorobots working quickly enough, one could build a DNA strand that will produce a perfect clone. The same issues will arise, or re-arise, if nanotechnology is successful in promoting cloning of DNA segments, cells, organs, or entire organisms.

See also: "... It is likely that nanotechnology's efforts will lead to twists in the assumptions that lead to the resolution of cloning issues in terms of genetic bioengineering. Policy makers should anticipate, now, that in setting the boundaries for bioengineered cloning, the need to foresee issues that will arise from cloning by nanotechnology and be ready to reevaluate cloning regulation before nanotechnology perfects its own methods of cloning. If we do not anticipate the nanotechnology problems, the debate will emerge in an environment like the current one: one filled with a frenzy and uproar, rather than in an atmosphere of reflection and deliberateness." [Joel Rothstein Wolfson, "Social and Ethical Issues in Nanotechnology: Lessons from Biotechnology and Other High Technologies", 22 Biotechnology Law Report 376, No. 4 (August 2003), pp. 13-14; at: http://www.blankrome.com/publications/Articles/WolfsonNanotechnology.pdf.] [Back]

6 For a lengthy report on the U.S.'s efforts towards the new field, see Converging Technologies for Improving Human Performance: Nanotechnology, Biotechnolog, Information Technology and Cognitive Science, NSF/DOC - sponsored report, edited by Mihail C. Roco and William Sims Bainbridge, National Science Foundation, and the U.S. Dept. of Commerce (June 2002), at: http://wtec.org/ConvergingTechnologies/Report/NBIC_report.pdf. [Back]

7 For full bibliographic references for these texts please see note 2 supra. [Back]

8 Alan Guttmacher, Life in the Making: The Story of Human Procreation (New York: Viking Press, 1933), p. 3. [Back]

9 See standard explanations of "methylation" in, e.g., O'Rahilly and Muller, 2001: "Cells differentiate by the switching off of large portions of their genome." (p. 39); Lewin, 2000: "Gene expression is associated with demethylation. Methylation of DNA is one of the parameters that controls transcription. This is one of several regulatory events that influence the activity of a promoter; like the other regulatory events, typically this will apply to both copies of the gene." (p. 678; also p. 603 ff); Strachan and Read, 1999: "Gene regulation as the primary function for DNA methylation; DNA methylation in vertebrates has been viewed as a mechanism for silencing transcription and may constitute a default position." (pp. 193 ff) [Back]

10 For standard explanations of "regulation", see, e.g., : (Carlson, 1999): "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." (p. 44). "... 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." (p. 46) " ... Some types of twinning represent a natural experiment that demonstrates the highly regulative nature of early human embryos, ... ." (p. 48) "...The relationship between the position of the blastomeres and their ultimate developmental fate was incorporated into the inside-outside hypothesis. The outer blastomeres ultimately differentiate into the trophoblast, whereas the inner blastomeres form the inner cell mass, from which the body of the embryo arises. Although this hypothesis has been supported by a variety of experiments, the mechanisms by which the blastomeres recognize their positions and then differentiate accordingly have remained elusive and are still little understood. If marked blastomeres from disaggregated embryos are placed on the outside of another early embryo, they typically contribute to the formation of the trophoblast. Conversely, if the same marked cells are introduced into the interior of the host embryo, they participate in formation of the inner cell mass. Outer cells in the early mammalian embryo are linked by tight and gap junctions ... Experiments of this type demonstrate that the developmental potential or potency (the types of cells that a precursor cell can form) of many cells is greater than their normal developmental fate (the types of cells that a precursor cell normally forms)." (p. 45); O'Rahilly and Muller, 2001: "Biopsy of an embryo can be performed by removing one cell from a 4-cell, or two cells from an 8-cell, embryo. This does not seem to decrease the developmental capacity of the remaining cells." (p. 37); Kay T. Elder, "Laboratory techniques: Oocyte collection and embryo culture" in Peter Brinsden (ed.), A Textbook of In Vitro Fertilization and Assisted Reproduction, 2nd edition (New York: The Parthenon Publishing Group, 1999): "Surprisingly, fragmented embryos, repaired or not, do implant and often come to term. This demonstrates the highly robust nature of the human embryo, as it can apparently lose over half of its cellular mass and still recover." (p. 197) [Back]

11 E.g., see Lewin, 2000: "The expression of genes is determined by a regulatory network that probably takes the form of a cascade. Expression of the first set of genes at the start of embryonic development leads to expression of the genes involved in the next stage of development, which in turn leads to a further stage, and so on until all the tissues of the adult are functioning." (p. 63; also pp. 914, 950). [Back]

12 Tom Strachan and Andrew P. Read, Human Molecular Genetics 2 (New York: John Wiley & Sons, Inc, 1999), pp. 508-509. [Back]

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