The desire of the scientific community for embryonic stem cells is not diminishing. Indeed, it is increasing, despite promising research with adult stem cells (scientists have already developed therapies for more than fifty diseases and disorders using stem cells from bone marrow and umbilical cord blood) and despite the fact that no useful embryonic stem-cell-based therapies currently exist or are even in FDA clinical trials.
Indeed, no amount of success in clinical trials using adult stem cells is likely to lessen the desire of the scientific community for embryonic stem cells--which is what has created the arguments that have dominated the medical news since 2001. For a large swath of the nation, creating human embryos (with the intent to experiment lethally upon them) is morally repugnant, but the scientific community seems unwilling to accept anything else.
But what if we could produce pluripotent stem cells, functionally identical to embryonic stem cells, without ever needing to create, experiment on, and destroy human embryos?
This is what a scientific procedure called "Altered Nuclear Transfer-Oocyte Assisted Reprogramming" (ANT-OAR) proposes to do. The proposal is based upon the premise that the identity and function of each cell in the human body depends, in the first place, on which subset of the approximately thirty thousand genes in the cell's nucleus is switched on or off. In other words, the gene sequence is not what is responsible for determining cellular identity, since the DNA is identical in nearly every cell in the human body. Rather it is the programming of the gene sequence that distinguishes cell types. This genetic programming is referred to as the cell's "epigenetic state."
We know the key epigenetic markers of pluripotent stem cells, and we know the markers of zygotes, which are one-celled human embryos. The stem cells that scientists seek are "pluripotent" (with the capacity of a cell to develop into most all the tissue types of the human body), while zygotes are "totipotent" (with the capacity to develop all the tissues of the human body, and extra-embryonic supporting tissues like the placenta, in an organized and self-directed manner). Using a procedure called "somatic cell nuclear transfer," defenders of ANT-OAR propose extracting the nucleus of a somatic cell (an adult body cell with the highly specified "epigenetic state" of the cell type from which it was extracted, say a skin cell) and then transferring it into an ooplast (an organic sac of cytoplasm left when the nucleus has been removed from an egg cell, or oocyte).
In the ANT-OAR proposal, before we transferred the somatic cell nucleus into the ooplast, we would preemptively alter its epigenetic state so that the genes expressed in the nuclear genome are consistent with pluripotent stem cells--but incompatible with totipotency and thus with the existence of a human zygote.
When scientists attempt cloning, they similarly remove the nucleus from an egg cell and insert a new nucleus. And they have discovered that the biochemical constituents in oocyte cytoplasm have the remarkable capacity to reprogram the epigenetic state of a transferred nucleus back to a state of totipotency. When the nucleus is transferred, the cytoplasm goes to work on the genome, and we are back to a totipotent zygote--the one-celled embryo whose moral status has caused so much concern.
For ANT-OAR, the key element in avoiding this is the altered nuclear transfer: The genetic material in the nucleus is preemptively altered to prevent its being affected by the reprogramming of the oocyte cytoplasm. The result is that the nuclear genome will never reach a state of totipotency--and thus we would create a pluripotent stem cell (from which, if all goes well, stem-cell lines can be derived) without ever creating a human embryo.
ANT-OAR defenders include such eminent thinkers as Hadley Arkes, Nigel Cameron, Maureen Condic, Kevin Fitzgerald, S.J., Kevin Flannery, S.J., Robert P. George, Alphonso Gómez-Lobo, Germain Grisez, Markus Grompe, John Haas, William Hurlbut, John Kilner, Patrick Lee, William E. May, Gonzalo Miranda, L.C., Archbishop John Myers, Tad Pacholczyk, Peter Ryan, S.J., William Saunders, Monsignor Stuart Swetland, and Thomas Weinandy. Many of them propose initial research using only nonhuman animal cells. If such research establishes that ANT-OAR can reliably be used to create pluripotent stem cells, they would then support research on human cells.
But there remain critics of the proposal. David Schindler, dean of the John Paul II Institute in Washington, D.C., has emerged as the principal Catholic critic of ANT-OAR. In the pages of Communio, several essays have appeared over the past year, with defenders of altered nuclear transfer, on one side, and with Schindler and his followers, on the other.
These opponents of ANT-OAR fear the procedure will create, not a pluripotent stem cell, but merely a badly disabled human embryo. Faced with the question of how can it be an embryo when it has the biological characteristics of a pluripotent stem cell, Schindler replies that he does not dispute that the end result of the process is a pluripotent stem cell; what he fears is that the entity brought into existence at the beginning of the process is a human embryo.
As it happens, the ANT-OAR proposal emerges from the same moral concerns that worry critics such as Schindler: It cannot be right to create human entities like embryos solely for the purpose of destroying them and extracting their components. So, the defenders hold, the entity brought into existence must look and act like a pluripotent stem cell in every relevant respect in order to be considered morally acceptable; if through animal trials the product exhibits embryonic characteristics, the procedure will be rejected.
The problem, for the critics, is in the way pluripotent stem cells would be created in ANT-OAR. Because the procedure is a form of somatic cell nuclear transfer, its product, Schindler argues, comes into existence in a "species-specific way." The process of ANT-OAR entails the fusing of an ooplast with a diploid somatic cell nucleus. In Schindler's view, this fusion is tantamount, in its effect, to conception.
In fact, he calls it a "mimicked conception." The fertilization of an egg by a sperm brings into existence a single-celled entity whose progenitor cells include an oocyte, and that possesses a complete human genome contained in a diploid nucleus. So, too, somatic cell nuclear transfer used to clone human embryos brings into existence a single-celled entity whose progenitor cells include an oocyte and that possesses a complete human genome contained in a diploid nucleus. And ANT-OAR also brings into existence a single-celled entity whose progenitor cells include an oocyte and whose diploid nucleus contains a complete human genome. Whenever we fuse an enucleated oocyte and a diploid nucleus, we "mimic conception"--bringing into existence an entity in a species-specific way and thus creating something that must be a human embryo.
This seems to mean that, for Schindler, the epigenetic state--the programming of the nuclear genome--is irrelevant to the nature of the entity. How this could be so is hard to see. The entity brought into existence through ANT-OAR is not totipotent until the specialized epigenetic state of the somatic cell nucleus is reprogrammed through its interaction with the oocyte cytoplasm, and, through preemptive genetic alterations, ANT-OAR sets out to prevent a state of totipotency from ever being realized.
Is it reasonable to hold, as Schindler does, that the entity brought into existence is in any case a human embryo? He claims that it is the embryo itself that directs its own epigenetic reprogramming back to a state of totipotency. ANT-OAR, he believes, can modify only the end of the process (to a state of totipotency or pluripotency, etc.), and thus the nature of the entity that originally came into existence in a species-specific way remains a human embryo.
The answer to Schindler's kind of complaint seems obvious. An entity is a human embryo only if the organic material is able to be human--if, in the language of Aristotle, it is apt to receive a substantial human form. Not every collection of organic material, even material that includes an oocyte and a diploid nucleus, can be a human being. We know this because we know that teratomas (naturally occurring tumors)--together with hydatidiform moles (disorganized entities that occur in humans and other animals as a result of certain types of defects in fertilization) and even oocytes themselves--are not human embryos, yet they all have as their starting material an oocyte and a diploid nucleus.
With respect to the biological conditions for the origins of a human zygote, this means the single-celled entity brought into existence must possess the inherent active biological disposition for self-directed development toward species maturity (including the capacity to develop all tissue types necessary for a differentiated human body and extra-embryonic supporting materials). In other words, the cell must be characterized by an epigenetic state of totipotency.
Biologically speaking, totipotency in a cell is a necessary and sufficient condition for concluding that that cell is a human embryo. It follows that even in human cloning, a human embryo does not come into existence until--among other things--the nuclear genome, through the reprogramming that takes place as a result of its interaction with oocyte cytoplasm, has attained a state of totipotency. The entity immediately after nuclear transfer and before nuclear reprogramming is not a human embryo that begins to self-direct its own process of reprogramming. Rather, it is akin to a body cell, with the epigenetic makeup of the donor somatic cell.
This suggests that the efficient cause of the reprogramming is not an embryo; the efficient cause is the complex of active constituents in the oocyte cytoplasm--the cytoplasm reprograms the nucleus. The product remains a single isolated cell until a state of totipotency is attained, at which point a human organism--a new whole, embryonic human being--comes into existence. In the case of ANT-OAR, the product never is totipotent. It is never apt to receive a substantial human form, and therefore it never becomes a human embryo.
One might still ask: Given the novelty of the procedure, its likeness in certain respects to human cloning, and the complexity and mystery of the progenitor cells used for its starting materials, isn't some doubt about the identity of the product of ANT-OAR justified? And if it is, are we not required to side with caution and refuse to proceed with experimentation that might produce disabled embryos?
If doubt were justified, then such caution would, in fact, be required. But ANT-OAR, as its defenders propose it, warrants no such doubt. It aims to create a cell that, from its first moment, exhibits organic properties biologically incompatible with totipotency. Schindler asserts that a single-celled entity can at once be a human embryo and yet manifestly not be (or ever have been) characterized by an epigenetic state of totipotency.
That requires one to believe that a cell's epigenetic identity is not a necessary condition for cellular identity--which, in turn, requires a dualistic anthropology inconsistent with the Christian understanding of humanity. It denies that the biological disposition of the organic material is a necessary condition for determining cellular identity. It implicitly holds that a cell can biologically look and behave in ways biologically indicative of a certain cell type, yet in fact be a wholly different kind of cell.
The property distinguishing a liver cell from a cardiac cell, or a retinal cell from a skin cell, is the programming of the genome. Yet no one would argue that a cardiac cell is a liver cell, or that a retinal cell is a skin cell, or that any of them are human embryos. The assumption that epigenetic identity does not determine cellular identity is clearly false--and moralists concerned about human embryos should welcome and support ANT-OAR as it moves to testing with animal cells.
E. Christian Brugger is assistant professor of theology at the Institute for the Psychological Sciences in Arlington, Virginia.
Copyright (c) 2006 First Things 163 (May 2006): 12-15.
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