The Altered Nuclear Transfer/Oocyte-Assisted Reprogramming poses ethical dilemma through the possible production and destruction of human embryos for research
American Life League has issued a statement regarding its analysis of the Alternative Pluripotent Stem Cell Therapies Enhancement Act (S. 2754) that is set to be debated in the U.S. Senate this Monday, July 17. The proposed bill would allow for the Altered Nuclear Transer/Oocyte-Assited Reprogramming (ANT/OAR) process invented by Dr. William Hurlbut.
“The Alternative Pluripotent Stem Cell Therapies Enhancement Act (S. 2754) is supposed to spare human embryos from abuse, but we oppose this bill because it allows for a technique that would actually create and then kill human embryos,” said American Life League president Judie Brown. “Furthermore, while some lawmakers believe that human embryos will be safeguarded from government research by the Dickey-Wicker Amendment, the amendment has been violated in the past and it may be violated again.”
Mouse trials of this process produced disabled embryos. If the protocol is used with human cells, it would create disabled human embryos who would be killed for their stem cells. This raises many serious moral concerns and should be especially troubling for Catholics in the field of science. Human embryologist C. Ward Kischer, Ph.D., emeritus professor from the University of Arizona, analyzed and objected to this use of ANT. Dr. Kischer said, “These examples of ANT do not resolve the moral issue and do not resolve the scientific issue of the continuum of human life.” He added that this ANT protocol, “Involves the destruction of human life.”
“Since ANT/OAR could be used to promote the creation and killing of disabled human embryos and could be complicit in harming women through egg harvesting, we urge senators to defend the sanctity and dignity of the human being by voting against the Alternative Pluripotent Stem Cell Therapies Enhancement Act (S. 2754),” said Brown.
The complete text of American Life League’s statement is below.
"The Alternative Pluripotent Stem Cell Therapies Enhancement Act (S. 2754) is supposed to spare human embryos from abuse, but we oppose this bill because it allows for a technique that would actually create and then kill human embryos," said American Life League president Judie Brown. "Furthermore, while some lawmakers believe that human embryos will be safeguarded from government research by the Dickey-Wicker Amendment, the amendment has been violated in the past and it may be violated again."
The scientific facts are behind American Life League's opposition to S. 2754.
Using the reference to the President's Council on Bioethics in S. 2754 means that the bill allows for altered nuclear transfer/oocyte assisted reprogramming (ANT/OAR), which is a variation on the cloning technique called somatic cell nuclear transfer or SCNT.
In the SCNT cloning process, the nucleus (the cell compartment containing the genome) of an adult cell is inserted into an egg cell that has had its nucleus removed. The result is a cloned embryo that is then killed in order to extract embryonic stem cells. This is objectionable on two counts. First, killing human embryos is wrong. Second, the harvest of the necessary eggs exploits and injures women. It also entails the risk of death.
William Hurlbut, M.D., a member of the President's Council on Bioethics and a professor at Stanford University, proposed ANT/OAR as a way around these moral difficulties. (We will refer to the process as ANT henceforth.) He strongly advocated this technique in the Spring 2005 issue of Perspectives in Biology and Medicine1, and then in a May 2005 paper from the President's Council on Bioethics2. At that time the procedure was "untested experimentally (even in animals)."
Hurlbut suggested that the genome be modified before transferring the somatic cell nucleus to the egg cell. By disabling the genes necessary for the organization and development characteristic of a human embryo, he stated:
The resulting biological entity, while being a source of pluripotent stem cells, would lack the essential attributes and capacities of a human embryo [emphasis in original]. For example, the altered nucleus might be engineered to lack a gene or genes that are crucial for the cell-to-cell signaling and integrated organization essential for (normal) embryogenesis. It would therefore lack organized development from the very earliest stages of cell differentiation. Such an entity would be a 'biological artifact,' not an organism.
The council's paper notes that there was some debate over whether the resulting entity would only be a disabled embryo or whether it would truly be a "biological artifact" that lacked the attributes of a human organism. However, it appeared at least conceptually possible that ANT could be used to derive the pluripotent stem cells typical of embryos, without creating or killing any human embryos.
"Sadly," said Judie Brown, "the experimental testing of ANT so far has rendered this benign hypothesis beside the point. The current research in mouse models does not fit the original vision of creating non-embryo entities. Rather, it has created embryos that, like the 'replicant' characters of the science fiction thriller Blade Runner, come with a 'termination date.'"
A paper3 by Alexander Meissner and Rudolf Jaenisch published in the scientific journal Nature describes the use of ANT in mouse models. While the experiment was successful in producing embryonic stem cells, it did so by producing disabled embryos. The original proposal envisioned the creation of entities without any developmental direction or organization; yet those created in this experiment were able to develop to the blastocyst stage before the genetic engineering resulted in their death.
The specific gene targeted in the mouse models was Cdx2, which is responsible for placental development. Thus, the blastocysts formed were unable to implant into the uterine lining. It is not known for sure, but is likely, that targeting Cdx2 in human ANT would have the same effect.
The scientists behind this study note that this application of ANT may not sate the objections it sought to placate "because the Cdx2-deficient embryo is not obviously abnormal before the onset of Cdx2 expression, this approach may not solve the ethical dilemma. Moreover, research with primate or human cells will be required to assess whether CDX2 is an optimal target for human application."
Following the publication of Meissner and Jaenisch's results, a piece4 in the journal Science also questioned whether these blastocysts were really the non-embryo entities sought. Hurlbut asserted that they were, but others on both sides of the embryonic stem cell debate dissented:
Turning off Cdx2 creates a severely disabled embryo but an embryo nonetheless, says Tadeusz Pacholczyk of the National Catholic Bioethics Center in Philadelphia. Stem cell researcher George Daley of Children's Hospital in Boston says the data Jaenisch and Meissner show suggest Pacholczyk has a point. 'The embryo that is established in the first few days is substantially normal,' he says.
Human embryologist C. Ward Kischer, Ph.D., emeritus professor from the University of Arizona, analyzed and objected to this use of ANT. He stated: "These examples of ANT do not resolve the moral issue and do not resolve the scientific issue of the continuum of human life." He added that this ANT protocol, "Involves the destruction of human life."
While it is conceivable that further ANT research with a different target gene(s) could provide an ethical source for embryonic stem cells, it is unlikely that such research will be pursued because Hurlbut and other bioethicists are supporting the protocol found in the Meissner and Jaenisch mouse trials. If the protocol is used with human cells, it would create disabled human embryos who would be killed for their stem cells.
Regarding the problem of gathering the necessary eggs, the paper by President's Council on Bioethics notes the objections, but offers only unlikely means of avoiding them. The paper stated:
There is, at least in theory, the possibility that human oocytes [eggs] can be obtained not from women egg donors by superovulation but from ovaries surgically removed from patients or harvested from cadavers. The oocyte precursors extracted from these ovaries could then be matured in vitro. Alternatively, the ovaries could be transplanted into animal hosts and eggs produced by hormonal stimulation of the animals. Research in this area is at a very preliminary stage.
"In short, the council's paper offers no practical alternatives to the current methods of egg harvesting," said Brown. "Even if ANT itself were used in a manner that clearly did not produce a human embryo, it would almost certainly still be complicit in the exploitation of women by harvesting their eggs."
"Since ANT/OAR could be used to promote the creation and killing of disabled human embryos and could be complicit in harming women through egg harvesting," Brown concluded, "we urge senators to defend the sanctity and dignity of the human being by voting against the Alternative Pluripotent Stem Cell Therapies Enhancement Act (S. 2754)."
- William B. Hurlbut. Altered Nuclear Transfer as a Morally Acceptable Means for the Procurement of Human Embryonic Stem Cells. Perspectives in Biology and Medicine 48.2 (2005) 211-228.
- Alternate sources white paper
- Alexander Meissner and Rudolf Jaenisch. Generation of nuclear transfer-derived pluripotent ES cells from cloned Cdx2-deficient blastocysts. Nature 439, 212-215 (12 January 2006), (online publication, 16 Oct 2005).
- Gretchen Vogel. Deriving 'Controversy-Free' ES Cells Is Controversial. Science 21 October 2005: Vol. 310. no. 5747, pp. 416 ? 417.
Release issued: 14 Jul 06