Why Accurate Human Embryology Is Needed To Evaluate Current Trends In Research Involving Stem Cells, Genetic Engineering, Synthetic Biology and Nanotechnology

Addendum: A Few Additional References for Sexual and Asexual Human Reproduction:

Human Sexual Reproduction:

** Ronan O'Rahilly and Fabiola Muller, Human Embryology & Teratology, 3rd ed. (New York: Wiley-Liss, 2001):

-- Recapitulation, the So-Called Biogenetic Law. The theory that successive stages of individual development (ontogeny) correspond with ("recapitulate") successive adult ancestors in the line of evolutionary descent (phylogeny) became popular in the nineteenth century as the so-called biogenetic law. This theory of recapitulation, however, has had a "regrettable influence on the progress of embryology" (G. de Beer).... According to the "laws" of von Baer, general characters (e.g., brain, notochord) appear in development earlier than special characters (e.g., limbs, hair). Furthermore, during its development an animal departs more and more from the form of other animals. Indeed, the early stages in the development of an animal are not like the adult stages of other forms but resemble only the early stages of those animals. The pharyngeal clefts of vertebrate embryos, for example, are neither gills nor slits. Although a fish elaborates this region into gill slits, in reptiles, birds, and mammals it is converted into such structures as the tonsils and the thymus (p. 16).

... (Fertilization is) the procession of events that begins when a spermatozoon makes contact with a secondary oocyte or its investments, and ends with the intermingling of maternal and paternal chromosomes at metaphase of the first mitotic division of the zygote. (p. 19).

-- Although life is a continuous process, fertilization... is a critical landmark because, under ordinary circumstances, a new, genetically distinct human organism is formed... (p. 31).

-- Fertilization takes place normally in the ampulla (lateral end) of the uterine tube (p. 31).

-- "The term 'pre-embryo' is not used here for the following reasons: (1) it is ill-defined because it is said to end with the appearance of the primitive streak or to include neurulation; (2) it is inaccurate because purely embryonic cells can already be distinguished after a few days, as can also the embryonic (not pre-embryonic!) disc; (3) it is unjustified because the accepted meaning of the word embryo includes all of the first 8 weeks; (4) it is equivocal because it may convey the erroneous idea that a new human organism is formed at only some considerable time after fertilization; and (5) it was introduced in 1986 'largely for public policy reasons' (Biggers)."... Just as postnatal age begins at birth, prenatal age begins at fertilization," (p. 88).

-- "Undesirable terms in Human Embryology": "Pre-embryo"; ill defined and inaccurate;
Use "embryo" (p. 12). [Note: O'Rahilly is one of the originators of The Carnegie Stages of Early Human Embryological Development, and has sat on the international committee for human embryology for decades]

** Lewin, Benjamin, Genes VII (New York: Oxford University Press, 2000):

-- "A genome consists of the entire set of chromosomes for any particular organism, and therefore comprises a series of DNA molecules, each of which contains a series of many genes. The ultimate definition of a genome is to determine the sequence of the DNA of each chromosome. (p. 4)

... "Genes not residing within the nucleus are generally described as extranuclear; they are transcribed and translated in the same organelle compartment (mitochondrion or chloroplast) in which they reside. By contrast, nuclear genes are expressed by means of cytoplasmic protein synthesis." (p. 81)

** Read, Andrew P., and Tom Strachan, Human Molecular Genetics 2, 2nd ed. (New York: John Wiley & Sons, Inc., 1999):

-- "In animal cells, DNA is found in both the nucleus and the mitochondria." (p. 10)

-- "The mitochondria also have ribosomes and a limited capacity for protein synthesis." (p. 18)

-- "The human genome is the term used to describe the total genetic information (DNA content) in human cells. It really comprises two genomes: a complex nuclear genome..., and a simple mitochondrial genome...Mitochondria possess their own ribosomes and the few polypeptide-encoding genes in the mitochondrial genome produce mRMAs, which are translated on the mitochondrial ribosomes." (p. 139)

Human Asexual Reproduction:

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

-- 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 [momozygotic twins] are clones... 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 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.... 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.

** Carlson, Bruce M., Human Embryology and Developmental Biology, 2nd ed. (St. Louis, MO: Mosby, 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).

-- 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. (p. 49)

-- 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).

-- 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).

-- 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 normalappearing tetraparental or hexaparental mouse. By various techniques of making chimeric embryos, it is even possible to combine blastomeres to produce interspecies chimeras (e.g., a sheep-goat). (p. 45).

-- 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).

-- Classic strategies for investigating developmental properties of embryos are (1) removing a part and determining the way the remainder of the embryo compensates for the loss (such experiments are called deletion experiments) and (2) adding a part and determining the way the embryo integrates the added material into its overall body plan (such experiments are called addition experiments). Although some deletion experiments have been done, the strategy of addition experiments has proved to be most fruitful in elucidating mechanisms controlling mammalian embryogenesis. (p. 46).

** Elder, Kay T. "Laboratory techniques: Oocyte collection and embryo culture," in ed. Peter Brinsden, A Textbook of in vitro Fertilization and Assisted Reproduction, 2nd ed. (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)

** Larsen, William, Essentials of Human Embryology (New York: Churchill Livingstone, 1998):

-- 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. (p. 325)

** Ronan O'Rahilly and Fabiola Muller, Human Embryology & Teratology (New York: Wiley-Liss, 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).

-- 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, (p. 37).

** National Bioethics Advisory Commission. Cloning Human Beings: Report and Recommendations. (Rockville, MD: June 1997):

-- The Commission began its discussions fully recognizing that any effort in humans to transfer a somatic cell nucleus into an enucleated egg involves the creation of an embryo, with the apparent potential to be implanted in utero and developed to term. (p. 3).

** National Institutes of Health. Background Paper: Cloning: Present uses and Promises, Jan. 29, 1998.

-- This experiment [producing Dolly] demonstrated that, when appropriately manipulated and placed in the correct environment, the genetic material of somatic cells can regain its full potential to direct embryonic, fetal, and subsequent development. (p. 3).

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