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> Comment on the "Official Website of Altered Nuclear Transfer(ANT)" (new)

> On the moral status of cells generated through Altered Nuclear Transfer 

> On the moral status of cells generated without genetic material from a male sperm cell (parthenotes)

> On the moral status of cells generated through Oocyte Assisted Reprogramming (OAR)


Comment on the "Official Website of Altered Nuclear Transfer(ANT)" (www.alterednucleartransfer.com)

April 10, 2006

  1. According to the ethical analysis of William B. Hurlbut, “just as the criteria of brain death are the cessation of integrated function, likewise with ANT the failure of formation of integrated function of a human species-typical kind exclude the ANT-construct from the category of a living human being.”

    This comparison can be objected. We think that only genetic or epigenetic alterations Directly Inhibiting the Appearance of Neural Activity (DIANA genomic anomalies) can exclude an ANT-construct from the category of a living human being. DIANA genomic anomalies frustrate the embryonic development on the path leading directly from the zygote to the emergence of the neural centers triggering fetal motility. By contrast, the comparison with the criteria of brain death does not hold for alterations frustrating the development on developmental branches that do not differentiate into brain cells, even if they may be lethal and lead indirectly to the failure of the brain development, as a consequence for instance of a defective heart or placenta. ANT-constructs that do not bear a DIANA alteration are sick living human beings. The same holds for constructs derived through Oocyte Assisted Reprogramming (OAR)

  2. By proposing a criterion based on DIANA anomalies we stress the importance of the developmental path leading to the emergence of neural activity. In so doing we coherently apply our principle that the potential for the neural activity specifically responsible for the spontaneous movements of a human organism is the relevant biological characteristic for ascertaining the presence of a spiritual soul. In accepting the clinical criteria of brain death one is in fact applying this very principle. 

  3. One can state that a definite alteration A precludes the generation of a human person only if one demonstrates that the alteration A frustrates the development on the path directly leading from the zygote to the appearance of neural activity, and not on secondary branches (leading to extraembryonic tissues, cardiac activity, blood circulation, connective tissue, etc.). In this sense, the level of 'insufficiency' Hurlbut proposes does not include this criterion and is less fundamental: for the time being, there is for instance no experimental basis to state that the inactivation of the gene Cdx2 or the overexpresion of the gene Nanog precludes directly the development of neural activity. On the basis of the available observations only epigenetic alterations leading to androgenotes or standard parthenotes can be considered DIANA defects.

  4. The discussion of the experimental results by Meissner and Jaenisch (Nature, published online 16.10.2005, doi:10.1038/nature04257) show that Hurlbut’s position is rather understood in the sense that  “any entity lacking the ability to implant is a pseudo-embryo and has no moral status”. However, if one generally accepts that an egg lacking the ability to implant has no moral status, then one cannot escape the conclusion that an embryo acquires the moral status only after implantation, which is indefensible. Harvesting ES from an ANT-construct engineered to the aim of preventing implantation by means of alterations other than DIANA ones is morally the same as harvesting ES from IVF embryos: in both cases one destroys human persons. 

  5. For practical purposes engineering a DIANA alteration represents a stronger constraint for ANT than alterations like Cdx2 inactivation or Nanog overexpression. In order to engineer DIANA alterations, it may well be that one must at least reproduce the parthenote’s epigenetic state.

We are convinced that the issue of distinguishing between a sick-embryo and a pseudo-embryo is a key one to break through in the fight for the rights of the embryo. ANT and OAR have the great merit of bringing this issue into focus. But it is crucial to establish a criterion allowing us to solve the issue. We propose the Direct Inhibition of the Appearance of Neural Activity (DIANA).

The Editors of Embryoperson
(J. Huarte Ph.D., M. Lang Physician, A. Suarez Ph.D.)

See the presentations in www.embryoperson.org :
DIANA genomic anomalies. Distinguishing between a sick embryo and a pseudo-embryo
Implantation irrelevant for moral status of the embryo.

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On the moral status of cells generated through Altered Nuclear Transfer

October 17, 2005

Alexander Meissner and Rudolf Jaenisch report first experimental results about the generation of pluripotent embryonic stem (ES) cells through Altered Nuclear Transfer (ANT) in mice (Nature, published online 16.10.2005, doi:10.1038/nature04257). This technique was proposed by the Stanford bioethicist William Hurlbut as a method of generating human ES cells without destroying human embryos. ANT creates abnormal nuclear transfer blastocysts that are inherently unable to implant into the uterus but would be capable of generating customized ES cells. Because of preimplantation lethality, the ANT-derived cells are supposed to be “pseudo-embryos” (non-embryonic biological entities), which do not deserve the moral status of true embryos.

However we think that Hurlbut’s proposal should be questioned. Indeed a human egg undergoing an abnormal and lethal growth in a very early developmental stage can very well be a sick true embryo and not only a “pseudo-embryo”. Engineering deliberately a sick embryo unable to implant is morally the same as simply not implanting a normal embryo.

In order to establish a scientific basis for distinguishing between a sick embryo and a “pseudo-embryo” we propose to consider the cells called parthenotes, which are generated by stimulating human eggs to start cleaving without the addition of any genetic material from a sperm or other separate source. These parthenotes can implant into the uterus wall, and develop till the stage when heart beating and blood circulation appears. Nevertheless, because of deficiencies in their epigenetic information, they cannot go beyond and unfold spontaneous fetal motility (Kono T. et al., 1996). Such parthenotes can be considered to share the same moral status as a brain dead adult. If one considers moral to obtain organs from a brain dead, nothing speaks against obtaining ES cells from such parthenotes.

We call SIENA¹ (Specific Inhibition of the Emergence of Neural Activity) a genomic alteration that tolerates healthy development till reaching heart beating and blood circulation, but inhibits the emergence of the brain activity responsible for spontaneous fetal motility. SIENA¹ alterations (as for instance those that parthenotes exhibit) generate pseudo-embryos. Other alterations generate sick embryos.

The fact that in a well functioning uterus an embryo unfolds spontaneous movements and not only heart beating and blood circulation, depends on the embryonic genetic and epigenetic information, and not on any information coming from the maternal organism. In this sense implantation is irrelevant for the moral status

The Editors of Embryoperson
(J. Huarte Ph.D., M. Lang Physician, A. Suarez Ph.D.)

¹Instead of this concept we use meanwhile the concept DIANA. See the presentation "DIANA genomic alterations"


References

Kono T. et al. (1996). Epigenetic Modifications During Oocyte Growth Correlates with Extended Parthenogenetic Development in the Mouse, Nature Genetics 13: 91–94; Gardner R.L. et al. (1990). Use of triple tissue blastocyst reconstitution to study the development of diploid parthenogenetic primitive ectoderm in combination with fertilization-derived trophectoderm and primitive endoderm, Genetical Research 56: 209-222.

 

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On the moral status of cells generated without genetic material from a male sperm cell (parthenotes).

September 22, 2005

As BBC News 2005/09/09 reports, a team of the Roslin Institute (Edinburgh) has created six parthenotes stimulating human eggs to start dividing like an embryo without the addition of any genetic material from a male sperm cell. The Edinburgh-based team hopes to obtain embryonic stem (ES) cells from the parthenotes and use them to investigate their potential in laboratory research and in medical treatments.

Parthenotes can implant into the uterus wall, and develop till the stage when heart beating and blood circulation appears. Nevertheless, because alterations in the genomic information (gene expression program), they cannot go beyond and unfold spontaneous fetal motility.

Therefore, parthenotes cannot be considered as true human embryos but should rather be considered to share the same moral status as a brain dead adult (see presentation). If one considers moral to obtain organs from a brain dead, nothing speaks against obtaining ES cells from parthenotes. By contrast, destroying in vitro fertilization embryos to harvest ES cells is a violation of the human rights.

Parthenotes are pseudo-embryos, i.e. non-embryonic entities exhibiting only an embryo-like development , and one should avoid to call them embryos. Also the term ‘virgin conception’ is confusing, for parthenotes should not be considered human persons.

The Editors of Embryoperson
(J. Huarte Ph.D., M. Lang Physician, A. Suarez Ph.D.)

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On the moral status of cells generated through Oocyte Assisted Reprogramming (OAR)

A number of advocates of embryo-free methods for generating pluripotent human have published a joint statement (Joint Statement 2005) supporting a proposal put forth by Markus Grompe: Oocyte Assisted Reprogramming (OAR) (Grompe and George 2005; Vogel 2005). In OAR one intends to fuse a somatic cell with an enucleated oocyte, but previously altering the input somatic cell or the oocyte so as to preclude formation of a human embryo. Grompe proposes to overexpress a gene like nanog before fusion, which might promote nuclear reprogramming of the donor somatic cell directly to an embryonic stem cell, and avoid generating any entity mimicking embryonic development.

For OAR to be considered morally unobjectionable, it is important to show that the single cells resulting through OAR are pluripotent stem cells and not single-celled embryos. Even if backers of OAR hope that this is the case, they acknowledge that one cannot reach this conclusion before obtaining clear results with animals.

Indeed, the fact that nanog is highly expressed in the ICM and in the ESCs but not in oocytes or single-celled embryos, does not necessarily mean that nanog overexpression in a oocyte leads to the complete failure of early embryonic development. The cells of the single-celled or two-celled stages and the ESCs derived from the ICM of a blastocyst have quite different gene expression patterns. For the time being, the only experiments with such stages did not involve ‘overexpression’ but ‘deletion’ of nanog, and show that this deletion does not prevent early cleavage stages of embryogenesis including formation of the ICM but does prevent the formation of an epiblast (Mitsui et al. 2003). This result stresses the importance of nanog expression for building the proper embryo. By contrast it is not yet known how behaves a fertilized egg resulting from an oocyte, which was injected with a nanog vector.

A nanog-expressing fertilized egg will most likely be capable of undergoing early cleavage otherwise OAR would be useless. But it may be difficult to distinguish the resulting cells from true embryonic blastomeres. In this case one could not rule out that such cells form a true embryo affected by an injure leading to preimplantation lethality, which could be rescued through an appropriate therapy as for instance tetraploid complementation. Then, additionally to nanog overexpression, it would be necessary to introduce a SIENA¹ alteration (see presentation) for granting an ethically unobjectionable method, the same way as for ANT. Therefore, experiments with nanog-expressing fertilized eggs in mice and primates are crucial. Only such experiments can tell us whether a morally unobjectionable OAR will be in the end more practical than generating pluripotent stem cells from parthenotes.

Notice also that up till now no ape is born through SCNT. This means that in primates reprogramming somatic cells is at least a highly defective technique. It is therefore important to exclude that OAR cells fail to develop because defective reprogramming rather than nanog expression.

The Editors of Embryoperson
(J. Huarte Ph.D., M. Lang Physician, A. Suarez Ph.D.)

¹Instead of this concept we use meanwhile the concept DIANA. See the presentation "DIANA genomic alterations"

References

Joint Statement. 2005. Production of Pluripotent Stem Cells by Oocyte Assisted Reprogramming. CBHD Posted June 20 (Accessed July 28, 2005 at: www.cbhd.org/resources/stemcells/jointstatment_2005-06-20.htm).

Grompe M. and R. George. 2005. Creative Science Will Resolve Stem-Cell Issues, Wall Street Journal, June 20: A14.

Mitsui, K. Y. et al. 2003. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113: 631-42.

Vogel G. 2005. Embryo-free techniques gain momentum, Science 309: 240-241.

 

 

     
   

 

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Last updated on 1 November 2005 22:00 +0100.