Dolly lab to create 'virgin birth' embryos

Dianne Irving’s Comments
Reproduced with Permission

[[Note: Below please note the convergence of scientific and ethical issues concerning the use of the early human embryo in research with the use of adult human subjects in research -- especially research concerning artificial reproductive technologies (ART). For full scientific references documenting my comments below, please see my recent New Jersey testimony, and my articles, "When do human beings begin? 'Scientific' myths and scientific facts", and "Biomedical Research With 'Decisionally Incapacitated' Human Subjects: Legalization of a Defunct Normative Bioethics Theory" which are all located on this web site. -- DNI]]



NewScientist.com news service:

Dolly lab to create 'virgin birth' embryos
http://www.newscientist.com/news/news.jsp?id=ns99993815


The team that cloned Dolly the sheep have been granted the UK's first stem cell research licence allowing the creation of human embryos from unfertilised eggs.

This process is called parthenogenesis - Greek for "virgin birth" - and occurs naturally in some reptiles and insects. It allows females to reproduce without males, as their eggs are prompted to develop into embryos without being fertilised by sperm.

[[Parthenogenesis used with human oocytes (presuming that is what they are really using) results in an embryo that is lacking the DNA instructions from a male sperm. Consequently, these embryos have been found to have several major genetic abnormalities, and die within weeks.

The scientific question is, if they are therefore using abnormal stem cells from these abnormal embryos, how can they validly correlate their findings with the supposed "healing" properties and products of normal stem cells? Would the data derived from research using abnormal stem cells misdirect the researchers' design of the protocol used to inject normal stem cells into human patients, thus negating the scientific data of such research using human subjects, as well as causing harm to them?

On the other hand, since these oocytes are diploid, researchers could experiment with them to learn how to reprogram the DNA so that it is differentiated (e.g., methylated) to mimic information that would have been contributed by a male sperm. Although specifics differ in different cloning techniques, this is essentially one of the major biological mechanisms responsible for the reproduction of Wilmut's Dolly (and since then several other animal clones). Theoretically, at least, that embryo would be a normal human embryo -- who could be cloned again by twinning, or who could be grown to the blastocyst stage (or beyond) to derive stem cells (and later, tissues and organs).

If what they are using are really female primitive germ line cells (which eventually mature into primary and secondary oocytes), since these cells are initially totipotent they can be cloned by twinning, and since they are diploid they could be cloned by nuclear transfer (GLCNT). -- DNI]]

Ian Wilmut and colleagues at the Roslin Institute, Edinburgh, will artificially stimulate human egg cells to undergo parthenogenesis and then take stem cells from the resulting embryos. Their aim is to develop the technology needed to maintain cell lines of human embryonic stem cells in the laboratory.

[[Since these stem cells will most likely be abnormal, they will merely succeed in maintaining abnormal cell lines of human embryonic stem cells in the laboratory which, if injected into human patients could be tumorogenic or cause other harm to those patients. And they would essentially have to maintain cultures of living human embryos (abnormal, normal?) in the laboratory as well. -- DNI]]

The one-year research licence was granted by the UK's Human Fertilisation and Embryology Authority on Tuesday. "Their objective is to look at developing stem cells per se," says Claire Rich, an HFEA spokeswoman.

[[Practically speaking, there is no such thing as stem cells "per se". First come embryos; only then come their stem cells. Ethically, that means that living human embryos must be destroyed in order to derive their stem cells for research. -- DNI]]

"Human embryonic stem cells have the potential to develop into any different kind of tissue in the human body," she told New Scientist, and this research could one day lead to treatments for diseases such as Parkinson's disease, heart disease and diabetes.

[[This is a claim that human embryonic stem cells are only pluripotent -- only capable of producing tissues, organs, but not new whole embryos. But that depends on the age of the embryo when his/her stem cells are removed. The blastomeres of the early human embryo from the 2-cell up to the blastocyst stage are totipotent -- i.e., if separated from the whole embryo they have the capacity to undergo "regulation", and revert (by, e.g., dedifferentiation, demethylation, reprograming) back to new whole embryos. In IVF research, this is called "blastomere separation". If the embryo has reached the free blastocyst stage (Carnegie Stage 3), most of the cells of the inner cell mass (ICM) of the blastocyst are still totipotent as well. If this blastocyst is split, then those totipotent cells too can undergo "regulation" and revert back to new human embryos. This is called "blastocyst splitting".

Both kinds of twinning of early human embryos is called "embryo multiplication", and occurs in natural human monozygotic twinning. "Twinning" is the most genetically accurate form of human cloning, because both the nuclear genetic material DNA) and the extranuclear genetic material (DNA) found in the mitochondria are found in both twins. That is why it is of such keen interest to IVF providers (rather than cloning by means of SCNT). -- DNI]]

Importantly, human embryos obtained through parthenogenesis "do not have the potential to develop into a child", says the HFEA. Therefore, destroying these embryos to obtain embryonic stem cells (ESCs) is not ending a potential human life. This ethical objection caused a number of countries to ban ESC research.

[[It is incredible, after all the scientific facts presented to that and similar committees over the years by scientific experts, that the British HFEA is still operating on the now scientifically rejected and flawed "pre-embryo" myth that was propagated by their Warnock Committee, as well as on the erroneous myth that "pregnancy" begins only at implantation -- the first myth grounding the second. Why is there still no professional or legal accountability demanded of these "committees"? Too much money, influence, prestige, research grants, Nobel prizes involved?

Any normal human embryo reproduced by parthenogenesis would be a "human child" immediately, not a "potential human child" -- regardless if the embryo were implanted or not. Thus destroying that child for his/her stem cells would be profoundly unethical.

While it is true that a woman undergoing artificial reproduction by IVF is not "pregnant" until the embryo is implanted in her womb or in her fallopian tube, in normal human reproduction "pregnancy" begins when the new human being begins -- immediately at fertilization in the woman's fallopian tube. The new embryo -- who already exists, and who already is a human being/child -- then makes his/her way to the woman's uterus (womb) and implants. Direct scientific quotations:

-- Ronan O'Rahilly and Fabiola Muller, Human Embryology &Teratology (New York: Wiley-Liss, 2001); [Note: O'Rahilly is one of the originators of The Carnegie Stages of Early Human Embryological Development, and has sat on the international Nomina Embryologica Committee for decades -- DNI).: "... 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)

-- KEITH MOORE AND T.V.N. PERSAUD, The Developing Human: Clinically Oriented Embryology (6th ed. only) (Philadelphia: W.B. Saunders Company, 1998): Sutton and Boveri declared independently in 1902 that the behavior of chromosomes during germ cell formation and fertilization agreed with Mendel's principles of inheritance. In the same year, Garrod reported alcaptonuria as the first example of mendelian inheritance in human beings. Many consider Garrod to be the Father of Medical Genetics. It was soon realized that the zygote contains all the genetic information necessary for directing the development of a new human being. (p. 12) ... Human development is a continuous process that begins when an oocyte (ovum) from a female is fertilized by a sperm (or spermatozoon) from a male. (p. 2); ... but the embryo begins to develop as soon as the oocyte is fertilized. (p. 2); ... Zygote: this cell results from the union of an oocyte and a sperm. A zygote is the beginning of a new human being (i.e., an embryo). (p. 2); ... Human development begins at fertilization, the process during which a male gamete or sperm ... unites with a female gamete or oocyte ... to form a single cell called a zygote. This highly specialized, totipotent cell marks the beginning of each of us as a unique individual. (p. 18) ... The usual site of fertilization is the ampulla of the uterine tube [fallopian tube], its longest and widest part. If the oocyte is not fertilized here, it slowly passes along the tube to the uterus, where it degenerates and is resorbed. Although fertiization may occur in other parts of the tube, it does not occur in the uterus. ... Human development begins when a oocyte is fertilized. Fertilization ... begins with contact between a sperm and a oocute and ends with the intermingling of maternal and paternal chromosomes ... of the zygote, a unicellular embryo. (p. 34) ... The zygote is genetically unique because half of its chromosomes come from the mother and half from the father. The zygote contains a new combination of chromosomes that is different from that in the cells of either of the parents. This mechanism forms the basis of biparental inheritance and variation of the human species. Meiosis allows independent assortment of maternal and paternal chromosomes among the germ cells. ... The embryo's chromosomes sex is determined at fertilization by the kind of sperm (S or Y) that fertilizes the ovum; hence it is the father rather than the mother whose gamete determines the sex of the embryo. (p. 37)

-- BRUCE M. CARLSON, Human Embryology and Developmental Biology (St. Louis, MO: Mosby, 1994): Human pregnancy begins with the fusion of an egg and a sperm. (p. 3); ... finally, the fertilized egg, now properly called an embryo, must make its way into the uterus (p. 3); ... The sex of the future embryo is determined by the chromosomal complement of the spermatozoon ... Through the mingling of maternal and paternal chromosomes, the zygote is a genetically unique product of chromosomal reassortment .. (p. 31); ... "After the eighth week of pregnancy the period of organogenesis (embryonic period) is largely completed and the fetal period begins. (p. 407)

-- BRUCE M. CARLSON, Human Embryology &Developmental Biology (St. Louis, MO: Mosby, 1999): "Human pregnancy begins with the fusion of an egg and a sperm, but a great deal of preparation [recedes this event. First both male and female sex cells must pass through a long series of changes (gametogenesis) that convert them genetically and phenotypically into mature gametes, which are capable of participating in the process of fertilization. Next, the gametes must be released from the gonads and make their way to the upper part of the uterine tube, where fertilization normally takes place. ... Finally, the fertilized egg, now properly called an embryo, must make its way into the uterus ....". (p. 2); ... Fertilization age: dates the age of the embryo from the time of fertilization. (p. 23) ... In the female, sperm transport begins in the upper vagina and ends in the ampulla of the uterine tube [fallopian tube] where the spermatozoa make contact with the ovulated egg. (p. 27) ... After the eighth week of pregnancy the period of organogenesis (embryonic period) is largely completed, and the fetal period begins." (p. 447). ... The sex of the future embryo is determined by the chromosomal complement of the spermatozoon. (If the sperm contains 22 autosomes and an X chromosome, the embryo will be a genetic female, and if it contains 22 autosomes and a Y chromosome, the embryo will be a male.) ... Through the mingling of maternal and paternal chromosomes, the zygote is a genetically unique product of chromosomal reassortment, which is important for the viability of any species. (p. 32)

-- WILLIAM J. LARSEN, Human Embryology (New York: Churchill Livingstone, 1997): In this text, we begin our description of the developing human with the formation and differentiation of the male and female sex cells or gametes, which will unite at fertilization to initiate the embryonic development of a new individual. ... Fertilization takes place in the oviduct [not the uterus]... resulting in the formation of a zygote containing a single diploid nucleus. Embryonic development is considered to begin at this point. (p. 1); ... "These pronuclei fuse with each other to produce the single, diploid, 2N nucleus of the fertilized zygote. This moment of zygote formation may be taken as the beginning or zero time point of embryonic development. (p. 17).

-- RONAN O'RAHILLY AND FABIOLA MULLER, Human Embryology &Teratology (New York: Wiley-Liss, 1994): Fertilization is an important landmark because, under ordinary circumstances, a new, genetically distinct human organism is thereby formed. (p. 5); ... Fertilization is the procession of events that begins when a spermatozoon makes contact with a secondary oocyte or its investments ... (p. 19); ... The zygote ... is a unicellular embryo. (p. 19); ... Thus the diploid number [in the zygote] is restored and the embryonic genome is formed. The embryo now exists as a genetic unity. (p. 20); ... ... The embryo enters the uterine cavity after half a week, when probably at least 8-12 cells are present. (p. 23); ... The embryonic period proper ... occupies the first 8 postovulatory weeks (i.e., timed from the last ovulation) ... The fetal period extends from 8 weeks to birth. (p. 55); ...

*** -- RONAN O'RAHILLY AND FABIOLA MULLER, Human Embryology &Teratology (3rd ed.)(New York: Wiley-Liss, 2001): Although life is a continuous process, fertilization ... is a critical landmark because, under ordinary circumstances, a new, genetically distinct human organism is formed when the chromosomes of the male and female pronuclei blend in the oocyte. This remains true even though the embryonic genome is not actually activated until 2-8 cells are present at about 2-3 days. ... During the embryonic period proper, milestones include fertilization, activation of embryonic from extra-embryonic cells, implantation, and the appearance of the primitive streak and bilateral symmetry. ... 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. ... Fertilization takes place normally in the ampulla (lateral end) of the uterine tube. (p. 31); ... [Events or phases of fertilization]: ... #12. Two pronuclei, which migrate to a central position in the ootid. #13. Coalescence of homologous chromosomes, resulting in a one-cell embryo. The two pronuclei do not fuse but their nuclear envelopes break down and form vesicles. The two groups of homologous chromosomes then move together and become arranged on the first cleavage spindle. [[[ i.e., the embryo begins before syngamy.]]] #14. The beginning of the first mitotic division of the zygote. The zygote is characteristic of the last phase of fertilization and is identified by the first cleavage spindle. It is a unicellular embryo and is a highly specialized cell. The combination of 23 chromosomes present in each pronucleus results in 46 chromosomes in the zygote. Thus the diploid number is restored and the embryonic genome is formed. The embryo now exists as a genetic unity. Items 12-14 in the list above have traditionally been regarded as constituting developmental stage 1. (p. 33); ... Prenatal life is conveniently divided into two phases: the embryonic and the fetal. ... [I]t is now accepted that the word embryo, as currently used in human embryology, means 'an unborn human in the first 8 weeks' from fertilization. Embryonic life begins with the formation of a new embryonic genome (slightly prior to its activation). (p. 87)

[[And from a current IVF text:]] -- Geoffrey Sher, Virginia Marriage Davis, Jean Stoess, In Vitro Fertilization: The A.R.T. of Making Babies (New York: Facts On File, 1998): The moment a sperm penetrates the egg's zona pellucida, a reaction in the egg fuses the zona and the perivitelline membrane into an impermeable shield that prevents other sperm from entering. ... Propelled by contractions of the fallopian tube, the dividing embryo begins its three- or four-day journey back to the uterus and continues to divide after it reaches the uterus. (The fertilization process occurs near the middle of the fallopian tube -- not in the uterus.) (p. 18) -- DNI]]

Human embryos have been created by parthenogenesis earlier in 2003, by a US biotech company called Stemron. Scientists managed to obtain early embryos, called blastocysts, from which stem cells can be harvested.

The licence awarded to the Roslin team does not permit the ESCs obtained to be used for any therapeutic purposes, but they can be used to test new medicines. A better understanding of how human eggs mature in the laboratory may also help women suffering from related fertility problems.

[[These "archane" (to some) theoretical and pure research issues must eventually be tested in and applied to human subjects for validation and application approvals as "standard medical treatment" by the FDA. Such research should continue to be defined as either "therapeutic research" or as "experimental research". Both are RESEARCH, not "standard medical treatment or "therapy". That means that they would be required to go through 4 phases of clinical trials with human subject patients.

But since there are international attempts to redefine "therapeutic research" as "health care" (see my article on the recently proposed but defeated statue in Maryland and the use of incompetent human subjects), then such RESEARCH could bypass all research ethical guidelines and conventions and be performed as "health care" on human patients in the privacy of research physicians' offices with no oversight. We now see the issues of abortion, the use of abortifacients, human embryo research, human cloning, human embryonic stem cell research, and the use (or abuse) of human subjects in research merge together as theory is translated into practice -- with no accountability or responsibility required of or enforced on those responsible for such research.

Finally, there is not a single case where the use of human embryonic stem cells have cured anything or anybody (as distinct from the use of adult and cord blood clinical trials that have had extraordinary success in human patients). Yet, as always, the suffering and desperation of sick and ill human citizens are exploited in this article again in order to gain "public" support and funding for research that they would normally consider unethical. Broad-ranging debates and discussions on the application of such research on human "patients" have yet to materialize. -- DNI]]


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