Human Embryology and Church Teachings

D. Human Sexual Reproduction: Carnegie States of Early Human Embryonic Development

The first to systematically study human embryos was Wilhelm His (Anatomie Menschlicher Embryonen 1880-1885, 3 vols.), and the first to stage them was Franklin Mall in 1914. Later George Streeter (Streeter 1942, p. 211; Streeter 1945, p. 27; Streeter 1948, p. 143) laid down the basis for the currently used Carnegie staging system, which was completed by Ronan O'Rahilly in 1973 and revised by O'Rahilly and Müller in 1987. The Carnegie Stages are often referred to as "the Bureau of Standards" of human embryology (O'Rahilly and Müller 2001, p. 3). Today they continue to be verified and documented by the international Terminologia Embryologica (formerly, Nomina Embryologica) committee, which consists of more than twenty experts academically credentialed specifically in human embryology from around the world. After reviewing the latest research studies in human embryology, their deliberations are published in the Terminologia Embryologica, part of the larger Terminologia Anatomica.

According to the CSEHED, the embryonic period is composed of twenty-three stages (CSEHED; also Irving 2006a, pp. 1-33). Approximately 90 percent of the more than 4500 structures of the adult body become apparent during the embryonic period. Of special note is Stage One-which begins when the sperm penetrates the oocyte and continues until just before the zygote starts its first cleavage cell division at syngamy, that is, when the 23 paternally- and 23 maternally-derived chromosomes from the haploid pronuclei in the single-cell embryo mingle and line up on opposite sides of the mitotic spindle fibers that appear in the zygote just before cell division (Edwards et al. 1992, pp. 994-998; Food and Drug Administration 2002; Gasser 2003; Levron at al. 1995, pp. 653-657; Michelmann et al. 1986, pp. 243-246; O'Rahilly and Müller 2001, Table 8-1, p. 89; Riley and Merrill 2005, p. 1; Sathananthan et al. 1991, pp. 4806-4810). Much human cloning and human genetic engineering takes place during Stage One of the developing human embryo, even before the formation of the zygote, or slightly later while the cells of the very early human embryo are still totipotent.

The characteristic feature of the embryo in Stage One is unicellularity; it is a single-celled organism. As documented by the CSEHED, "Embryonic life commences with fertilization, and hence the beginning of that process may be taken as 'the point de depart' of stage 1." Despite the small size and weight of the organism at fertilization, the embryo is "schon ein individual-spezifischer Mensch" ("already an individual and specifically human person") (Blechschmidt 1963; Blechschmidt 1973; Blechschmidt 1982, pp. 171-181). Again, "It is to be remembered that at all stages the embryo is a living organism, that is, it is an on-going concern with adequate mechanisms for its maintenance as of that time" (Streeter and Heuser 1951, p. 165).

Fertilization, which normally takes place in the uterine (fallopian) tube, is the procession of events that begins when a spermatozoon mature sperm makes contact with an oocyte and ends with the intermingling of maternal- and paternal-derived chromosomes at metaphase of the first mitotic (cell) division of the zygote. Stage One of the embryo thus includes: (a) the penetrated oocyte - the term used once a haploid spermatozoon has penetrated the diploid oocyte (causing the diploid oocyte to half its number of chromosomes to 23) and, strictly, "after the individual plasma membranes of the sperm and of the oocyte have become one"; (b) the ootid, characterized by the presence of the male and female haploid pronuclei (each pronuclei containing 23 chromosomes); and (c) the zygote, which characterizes the last phase of fertilization. At syngamy, or when the chromosomes from the male and female pronuclei mingle, the first cleavage spindle (mitotic spindle) forms rapidly, the two pronuclear envelopes (outer membranes of the individual haploid male and haploid female pronuclei) break down, and the two groups of chromosomes move together (46 chromosomes in all) and assume positions on the first cleavage spindle. Thus the zygote lacks a nucleus. In the human this initial cleavage (cell division), which heralds the onset of Stage Two, normally occurs in the uterine (fallopian) tube (CSEHED at; also Carlson 1999, pp. 24-37; Larsen 1998, pp. 12-14; Moore and Persaud 1998, pp. 34-37; O'Rahilly and Müller 2001, pp. 31-33, 19-35). Also see Carnegie Stages online from University of Fribourg, Switzerland, "Human Embryology," 1999).

The age at Stage Two is believed to be approximately 1 1/2 -3 days post ovulatory days. The range is probably 1-5 days (Sundstrom, Nilsson, and Liedholm, 1981). in vitro, 2 cells may be found at 1½ days (CSEHED at; Carlson 1999, fig. 3-2A; Larsen 1998, p. XI). Stage Two comprises embryos from two cells up to the appearance of the blastocystic cavity within the embryo. Successive cleavage divisions of the cells (blastomeres) occur asynchronously (not in perfect multiples, but alternately) (Carlson 1999, p. 38). Separation of the cells of the early embryo is believed to account for about one-third of all cases of natural human in vivo monozygotic twinning (identical twins), a natural form of human cloning. (Fraternal or dizygotic twins are reproduced by two sperm fertilizing two oocytes) (Commonwealth of Australia 1986; Commonwealth of Australia 2001; Brinsden 1999, p. 421; Campbell et al. 1997, pp. 18-19; Corner 1955, pp. 933-951; Council of Europe 1998, p. 2; Geraedts et al. 2001, pp. 145-150; Irving 2005, pp. 1-36; National Institutes of Health 1998, p. A-3; Robertson 1994, p. 6; Strachen and Read 1999, pp. 508-509). The embryo proceeds along the uterine tube and enters the uterine cavity (womb) 3-4 days after ovulation, comprised of 8-12 cells or more. The primary factor for determining one of the two alternative routes of cell specialization or differentiation (specialization as the outer layer of cells of the embryo, or trophoblast, or specialization as the cells of the inner cell mass of the embryo) is probably the position that a given cell occupies (CSEHED at; also Carlson 1999, pp. 38-48; Larsen 1998, pp. 14-15; Moore and Persaud 1998, p. 41; O'Rahilly and Müller 2001, pp. 37-39).

At about 4 days Stage Three consists of the free-floating, unattached blastocyst, a term used as soon as a cavity in the embryo can be recognized by light microscopy. The outer membrane, or zona pellucida, may be either present or absent. in vitro the blastocyst emerges from the zona at about 6-7 days, commonly referred to as hatching. The whole blastocyst is the embryo, not just the cells of the inner cell mass, whose cells have now clearly differentiated into at least two types: trophoblastic (outer layer) and embryonic cells proper (the inner cell mass that is observable by light microscopy). The inner cell mass constitutes a germinal mass of various potentialities (totipotent and pluripotent), which continues for a time to add cells to the outer trophoblast. The inner cell mass also gives origin to the hypoblast, and its remainder constitutes the epiblast. The epiblastic cells soon become aligned into the germ disc. Duplication of the inner cell mass (sometimes referred to as blastocyst splitting, embryo multiplication, or embryo splitting) accounts for most instances of natural human in vivo monozygotic identical twinning (Bulmer 1970; Corner 1955, pp. 933-951), another form of natural cloning. Note that the blastocyst has not yet tried to implant in the uterus (CSEHED at; also Carlson 1999, p. 48; Larsen 1998, p. 15; Moore and Persaud 1998, pp. 41-42; O'Rahilly and Müller 2001, pp. 39-40).

Stage Four is reserved for the attaching blastocyst, which is about 5-6 days old at the beginning of implantation. Implantation (Stages Four and Five) includes the dissolving of the zona pellucida (outer membrane), contact and attachment between the blastocyst and the endometrium (lining) of the uterus, and penetration and migration of the embryo through the endometrium. These early embryos may be surrounded by an intact outer membrane, which disappears so that the embryo can begin implantation. The cytotrophoblast and the syncytiotrophoblast become distinguishable, and the amniotic ectoderm develops (CSEHED at; also Carlson 1999, p. 48; Larsen 1998, pp. 15-16; Moore and Persaud 1998, p. 42; O'Rahilly and Müller 2001, pp. 40-41).

Stage Five comprises embryos that are about 7-12 days old. Implantation, which began in Stage Four, is the characteristic feature of Stage Five. Both maternal and embryonic tissues are involved, and an amniotic cavity is present. The chief function of the amnion is not mechanical protection but rather "the enclosing of the embryonic body in a quantity of liquid sufficient to buoy it up and so allow it to develop symmetrically and freely in all directions" (Mossman 1937, pp. 129-246). At the caudal margin of the epiblast, the earliest differentiated cells of the later primitive streak appear, which will give rise to the extra-embryonic mesoderm of the chorion, chorionic villi, and body stalk (Luckett 1978, pp. 59-97). The embryonic disc formed is composed of the epiblast and the primary endoderm. On the ventral side of the embryonic disk, extra-embryonic endoderm grows around to enclose a cavity called the primary umbilical vesicle, or yolk sac. [The term yolk sac has been scientifically rejected (O'Rahilly and Müller 2001, p. 12).] The primary umbilical vesicle will provide most of the lining of the alimentary and respiratory systems. It is the site of the earliest blood vessels and blood cells as well as of the formation of fetoproteins, appears to be the place of origin of the totipotent future sex gametes, and will become part of the later adult gut. If duplication of the embryo occurs after the differentiation of the amnion, the resulting twins would share an umbilical cord and amniotic sac. It has been estimated that the frequency of monoamniotic twins among monozygotic twins is about 4 percent (Bulmer 1970). In about one in every 400 monozygotic twin pregnancies, the duplication is incomplete, and conjoined (Siamese) twins result, sometimes forming many weeks post-fertilization (CSEHED at; also Baron et al. 1990, pp. 9-22; Carlson 1999, pp. 48-60; Larsen 1998, pp. 15-16; Moore and Persaud 1998, pp. 41-45, 154-162; O'Rahilly and Müller 2001, pp. 43-46, 53-55; Wilder 1904, pp. 387-472).

At about 13 days the appearance of recognizable chorionic villi is used as the criterion for Stage Six. The secondary umbilical vesicle, the embryonic disc, and the extra-embryonic mesoblast develop. The blood vascular system first derives from extra-embryonic areas, and the amnion is well formed. With the appearance of the primitive streak during Stage Six, certain cells of the epiblast enter the streak, and the remaining cells on the dorsal aspect of the embryo will become the embryonic ectoderm. Some of the cells of the endoderm may be primordial germ cells (future sex gametes). The primitive streak is a proliferation of cells lying in the median plane in the caudal region (toward the posterior end of the embryo) of the embryonic disc. Its essential features are the pluripotential nature of the cells that compose it and the continued segregation of more specialized cells that migrate, or delaminate, from the less specialized remainder. The primitive streak enables cells from the outer layer of the embryo to pass inside and become mesodermal endoderm. The primitive streak is believed to be an entrance where cells of the epiblast move toward the streak, folding in takes place at the streak, and subsequently cells migrate to both homolateral (same side) and heterolateral (opposite side) mesoderm. Zones have been established for future ectoderm, mesoderm, endoderm, and notochord. With the establishment of bilateral symmetry, the embryonic disc, in addition to its back and belly surfaces, now has rostral (top) and posterior (bottom) ends and right and left sides. Although the main bulk of the embryonic mesoblast is believed to come by way of the primitive streak, other sources are not excluded. The prechordal plate, the cloacal membrane, and the connecting stalk (the later umbilical cord) also form. At about 18 days, the primitive streak begins to recede (CSEHED at; also Carlson 1999, pp. 60-64; Larsen 1998, 21-34; Moore and Persaud 1998, pp. 48-51; O'Rahilly and Müller 2001, pp. 46-50).

At Stage Seven, about 19 days, the notochordal process (primitive axis of the body below the primitive groove) becomes visible, and the formation of blood begins. The allantoic diverticulum (a tubular formation in the posterior part of the hind gut of the embryo initially derived from the outer layer of the blastocyst, or trophoblast layer) becomes definite; this persists in the adult as the median umbilical ligament (a band of tissue that connects bones or supports organs), blood cells, and urinary bladder (CSEHED at; also Carlson 1999, p. 64-73; Larsen 1998, pp. 34-40; Moore and Persaud 1998, pp. 68-80; O'Rahilly and Müller 2001, p. 57).

At this point it is clear that the scientific bases of philosophical and theological arguments for "delayed personhood", especially those in bioethics, a new quasi-ethics created by the U.S. Congress in 1978 (Irving 1999c; Irving 2002b, pp. 1-84; Jonsen 1998, pp. 90-122; Neuhaus 2002, pp. 71-72; Rothman 1991, pp. 168-189; Saletan 2001), are erroneous and completely without scientific merit. The "science" used has been formally rejected as unscientific and misleading by the international nomenclature committee on human embryology for years. This includes such arguments containing the various pre-embryo and individuality claims (Grobstein 1985, pp. 213-236; Grobstein 1988, p. 33; McCormick 1975, pp. 34-35; McCormick 1991, pp. 1-15), the biogenetic law or "ontogeny recapitulates phylogeny", (see Irving 2001a, pp. 1-24), and "seeds" or "beings-on-the-way" (Wallace 1989, pp. 23-53). Similarly, assertions that the early human embryo is not an organism but just a cell or a ball of cells (National Academy of Sciences 2002a, b; Varmus 1999; Weissman 2003; West 2001 and 2007) are erroneous and without scientific merit (Biggers 1990, pp. 1-6; de Beer 1958; Irving 1991, pp. 1-400; Irving 1993a, pp. 18-46; Irving 1999a, pp. 22-47; Irving 2001a, pp. 1-24; Irving 2001b, pp. 1-12; Irving 2001c, pp. 1-17; Irving 2001d, pp. 1-32; Irving 2003, pp. 1-42; Irving 2004a, pp. 1-31; Kischer and Irving 1997, pp. 4-13, 129-184, 224-247, 248-257, 267-282; O'Rahilly and Müller 2001, pp. 16, 88). It should be pointed out that a host of scientists, organizations, and countries now routinely use the false scientific term "pre-embryo", or its various substitutes, as justification for doing embryonic research (American Fertility Society 1986; American Medical Association 1994; American Society for Reproductive Medicine 2007, pp. S52-S58; British House of Lords 2001; California Advisory Committee 2002; Gerontology Research Group 2001; McLaren 1984; National Institutes of Health 1994; National Academy of Sciences 2002a, b; National Bioethics Advisory Commission 1997; New Zealand 2004; Parliamentary Assembly of the Council of Europe 1986 and 1989; Pia Saldeen and Per Sundstrom 2005, pp. 584-589; The Twins Foundation 1994; Varmus 1999; Warnock Report 1984; Weissman 2003; West 2001 and 2007; Zaninovic et al. 2005, p. S476). It would seem that professional ethics across the academy has suffered (Irving 1993a, 18-46; Irving 1993b, pp. 243-247; Irving 1993c, pp. 77-100; Irving 1995, pp. 193-215; Irving 2004b, pp. 1-65).

The remaining Carnegie Stages are summarized more briefly as follows. Stage Eight, about 23 days: the embryonic disc is piriform, or oval-shaped; the primitive pit (primitive digestive cavity) appears; the neural folds may begin to form; and the notochordal and neurenteric canals are generally detectable. Stage Nine, about 25 days: the embryo has the shape of the sole of a shoe as seen from the back; the mesencephalic (midbrain) flexure begins and the otic, or ear, disc forms; the embryo begins to be lordotic (the curvature of the primitive spine becomes concave); the neural groove (caused by the folding in of the neural plate) is evident; the three major divisions of the brain are distinguishable; and the heart begins to develop. Stage Ten, about 28 days: fusion of neural folds begins; the otic pit develops; pharyngeal arches 1 and 2 are visible on the surface; optic, thyroid and respiratory primordia begin to develop; the cardiac loop begins to appear; and the intermediate mesoderm becomes visible. Stage Eleven, about 29 days: the rostral neuropore (open end of the neural tube near the head of the embryo) closes; the otic (eye) pit is still open; the optic vesicles develop; sinus venosus (common receptacle of veins) begins; and the mesonephric (excretory) duct and tubules appear. Stage Twelve, about 30 days: the caudal neuropore closes; four pharyngeal arches are visible; upper limb buds are appearing; secondary neurulation commences; the lung bud appears; and the cystic primordium (urinary and gall bladder) and dorsal pancreas become distinguishable. Stage Thirteen, about 32 days: the otic vesicle is closed; the lens disc is usually not yet indented; four limb buds are usually visible; retinal and lens discs develop; the septum primum and foramen primum are distinct in the heart; and the right and left lung buds are recognizable. Stage Fourteen, about 33 days: the lens pit appears; the endolymphatic (pertaining to the ear) appendage becomes defined; the upper limb buds are elongated and tapering; the optic cup develops; the adenohypophysial (gandular portion of the future pituitary gland) pouch is defined; and the ureteric bud appears. Stage Fifteen, about 36 days: the lens pit is closed; the nasal pit is appearing; the hand plate is forming; the future cerebral hemispheres become defined; retinal pigment becomes visible; and lobe buds appear in the bronchial tree (primitive lung). Stage Sixteen, about 39 days: retinal pigment is visible in the intact embryo; nasal sacs face ventrally; the foot plate appears; the epiphysis cerebri, or pineal gland, develops; neurohypophysial evagination is visible; and the lobar bronchi are evident. Stage Seventeen, about 41 days: the head is relatively larger and the trunk is straighter; the nasofrontal groove (origin of nose and facial bones) and the auricular hillocks (part of future ear) are distinct; finger rays become visible; chondrification (formation of cartelage) begins in bones such as the humerus, radius, and some vertebral centra; segmental bronchial buds develop; and the vermiform (worm-shaped) appendix becomes visible. Stage Eighteen, about 44 days: the body is more cuboidal, or cube-shaped; the digital plate of the hand is notched; toe rays begin to appear; the oronasal (mouth and nose) membrane develops; one to three semicircular ducts are present in the internal ear; and the septum secundum (a temporary dividing wall in the right side of the primitive heart) and the foramen ovale (natural openings) are distinct in the heart. Stage Nineteen, about 46 days: the trunk is elongated and straightening; limbs extend nearly directly forward; toe rays are prominent, but interdigital notches have not yet appeared; the olfactory bulb develops; the cartilaginous otic capsule is visible; and the posterior epithelium (covering) of the cornea begins to develop. Stage Twenty, about 49 days: the upper limbs are longer and bent at the elbows; nerve fibers reach optic chiasma (crossing over); and S-shaped renal vesicles are visible in metanephros, or future kidneys. Stage Twenty-One, about 51 days: hands approach each other; fingers are longer; feet approach each other; the cortical plate becomes visible in the brain; the substania propria (fibrous, tough, transparent main part) of the cornea develops; and glomerular capsules develop in metanephros. Stage Twenty-Two, about 53 days: the eyelids and the external ears are better developed; the adenohypophysial (pertaining to the pituitary gland) stalk is now incomplete; scleral (white part of the eyeball) condensation is visible; and some large glomeruli are present in metanephros. Stage Twenty-Three, about 56 days: the head is more rounded; the limbs are longer and better developed; humerus (bone that extends from the shoulder to the elbow) presents all cartilaginous phases; the bone collar of humerus has not yet been eroded through completely; secretory tubules of metanephros (permanent embryonic kidney) become convoluted; and numerous large glomeruli are present (CSEHED at; also Carlson 1999, pp.60ff; Larsen 1998, 45ff; Moore and Persaud 1998, pp. 85ff; O'Rahilly and Müller 2001, pp. 57-111 and ff).

After the embryonic period, the fetal period comprises the development of the human fetus from nine weeks until birth (Carlson 1999, p. 447; Larsen 1998, p. 317; Moore and Persaud 1998, p. 107; O'Rahilly and Müller 2001, p. 103).

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