A Reader’s Response on ANT

Filed in Science, Social IssuesTags: Clone The Truth, Cloning, Sanctity of Life, Stem Cells

Parableman stops by this post about the stem-cell issue, that I submitted to Christian Carnival CIX. He has some thoughts on ANT:

I don't think it's as clear on ANT. The way it's usually been described from what I've read is that they alter the genetic information before they import the nucleus. The genetic engineering thus takes place before there's any orgnanism, and I think what they're doing is not like producing a human being that is alive and unable to grow but more like producing a corpse with still-living material. But it's not producing a corpse by killing an organism. It's more like producing a corpse by putting together materials that are incapable of being an organism. That doesn't sound anywhere near as problematic as the way you describe it. I think there are ethical worries, but I think it's misleading to describe it as a living embryo and then preventing it from growing. Does it count as an organism at all? I don't think that's as easy a question as you're making it sound. Current understandings of what it takes to answer that seem to me to be indeterminate on this sort of question.

I appreciate all input, and I'd like to discuss. On this statement:

The way it's usually been described from what I've read is that they alter the genetic information before they import the nucleus. The genetic engineering thus takes place before there's any orgnanism...

Let's take a look at what actually happens in the process. The method used here is still Somatic Cell Nuclear Transfer (SCNT):

The nucleus of a cell contains DNA, which acts roughly as its blueprint (although unlike an actual blueprint, these instructions are greatly affected by environment as well as other factors not yet fully understood and can change over time). In somatic cell nuclear transfer the nucleus of an unfertilized egg is removed or destroyed. A somatic cell (a cell other than a sperm or egg cell) is then inserted into the enucleated egg and the two cells fuse together.

Altered Nuclear Transfer (ANT) modifies not the process, but one of the components: namely, the somatic cell implanted in the nucleus-free egg. What, then, is a somatic cell?

A somatic cell is generally taken to mean any cell forming the body of an organism: the word "somatic" is derived from the Greek word s?ma, meaning "body". Somatic cells, by definition, are not germline cells and cannot divide or differentiate to produce a new generation of offspring under any circumstances. In mammals, germline cells are the sperm and ova (also known as "gametes") which fuse during fertilisation to produce a cell called a zygote, from which the entire mammalian embryo develops. Every other cell type in the mammalian body – apart from the sperm and ova, the cells from which they are made (gametocytes) and undifferentiated stem cells – is a somatic cell; internal organs, skin, bones, blood and connective tissue are all made up of somatic cells.

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Somatic cells can also be defined by the amount of genetic material they contain, which in mammals is always twice as much as contained in a germline cell. The genetic information in human somatic cells is packaged into 23 pairs of chromosomes. Human germline cells contain exactly half this amount, i.e. 23 single chromosomes. This means that when an ova and sperm fuse, they produce a zygote with 23 pairs of chromosomes.

The problem, then, that I have with your statement that "genetic engineering thus takes place before there's any organism" is that the SCNT process (altered or otherwise) requires a genetically fully human organism to be present at every step. The process starts with a genetically fully human somatic cell, implants it into an enucleated human gamete, creating a genetically fully human embryo. Both the original somatic cell and the resulting embryo contain 23 pairs of chromosomes.

ANT does not modify this genetic makeup of either the somatic cell nor of the resulting embryo. This point is critical, and ANT proponents (including Dr. Hurlbut) try to disguise this fact:

Altered Nuclear Transfer uses the technology of NT but with a preemptive alteration that assures that no embryo is created.

The somatic cell nucleus or the enucleated egg contents (cytoplasm) or both are first altered before the somatic cell nucleus is transferred into the egg. The alterations cause the somatic cell DNA to function in such a way that no embryo is generated, but pluripotent stem cells (PSCs) are produced.

This point is critical, and ANT proponents' position here is untenable. Stem cells are not "formed", they are - by definition - derived from an embryo. Definition of embryonic stem cells:

Embryonic stem cells (ESCs) are stem cells derived from the undifferentiated inner mass cells of a human embryo (sometimes called a blastocyst, which is an early stage embryo - approximately 1 week old in humans - consisting of 50-150 cells).

To be clear, here is the definition of a blastocyst:

A mammal develops from a single cell called a zygote, which results from an oocyte (egg) being fertilized by a single sperm. The zygote is surrounded by a strong membrane of glycoproteins called the zona pellucida which the successful sperm has managed to penetrate.

The zygote undergoes cleavage, increasing the number of cells within the zona pellucida. When there are about 4 to 16 cells, the embryo is in the morula stage. When the number of cells reaches 40 to 150, a central, fluid-filled cavity (blastocoel) forms. The zona pellucida begins to degenerate. This stage in the developing embryo is the blastocyst, and lasts approximately until the implantation in the uterus. The outer cells develop into the placenta.

The definition of a zygote:

A zygote ...is a cell that is the result of fertilization. That is, two haploid cells—usually (but not always) an ovum from a female and a sperm cell from a male—merge into a single diploid cell called the zygote (or zygocyte).

Animal zygotes undergo mitotic cell divisions to become an embryo.

And finally, the definition of embryo:

An embryo ...is a diploid eukaryote in its earliest stage of development.

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In organisms that reproduce sexually, once a sperm fertilizes an egg cell, the result is a cell called the zygote that has all the DNA of two parents. In plants, animals, and some protists, the zygote will begin to divide by mitosis to produce a multicellular organism. The term embryo refers to the early stages of this development, after the zygote has divided at least once, but before the process has completed to produce a new individual.

Apologies for the copious quoting, but it is important that the meanings of each of these terms are understood.

Now, back to Hulburt's defense:

Why the cell produced by ANT is not an embryo and cannot produce an embryo:

Because the alterations are made before the somatic cell nucleus is transferred into the egg, the result of the ANT procedure is a cell whose DNA and pattern of gene expression are not only altered, but altered from the very start. Therefore from the very start it does not have the capacity for the integrated organization and coordinated development that characterize a human embryo. This is clearest in the case of ANT-OAR where the cell directly behaves like a pluripotent cell.

Elsewhere, in his bioethics presentation to the President, he gives this explanation for why the result of ANT is not a "living organism":

The moral argument for Altered Nuclear Transfer is grounded in the emerging science of systems biology. According to this radical revision of our prevailing reductionistic views, an organism is a living whole, a dynamic network of interdependent and integrated parts.

There are essential subsystems of growth (cells, tissues and organs), but a living being is more than the sum of its parts, and the parts are dependent on the integrated unity of the whole. Fully constituted, the organism is a self-sustaining and harmonious whole, a unified being with an inherent principle of organization that orders and guides its continuity of growth. In the human embryo, this principle of organismal unity is an engaged and effective potential-in-process, an activated dynamic of development in the direction of the mature human form. Incompletely constituted or severed from the whole, subsystems with partial trajectories of development may temporarily proceed forward with a certain biological momentum. Ultimately, however, they fail to rise to the level of the coordinated coherence of a living organism and become merely disorganized cellular growth.

This is dangerous ground, for several reasons. Unaltered, the somatic cell and egg would fuse, begin mitosis, and the resulting embryo would proceed on to further development. Altered, the somatic cell and egg would fuse, begin mitosis (note, again, at this point, the organism is an embryo) - identical to the unaltered organism, except that it has been genetically robbed of its inherent ability to develop. Let me reiterate: the moment a zygote containing 23 paired human chromosomes divides, an embryo exists; a non-viable embryo, to be sure - but an embryo, nonetheless. ANT proponents can argue the moral impact of the creation of a non-viable embryo, but to claim that ANT does not produce an embryo is a fallacy. Two arguments:

  • First, NT produces a zygote, which upon first division becomes - by definition - an embryo.
  • Second, ANT does not produce stem cells directly, but an organism containing stem cells. As was demonstrated above, the entity containing stem cells is an embryo at the blastocyst stage.

So, coming back to Parableman's comment:

I think what they're doing is not like producing a human being that is alive and unable to grow but more like producing a corpse with still-living material. But it's not producing a corpse by killing an organism. It's more like producing a corpse by putting together materials that are incapable of being an organism.

Hopefully you can see now that the rationalization for the entity created from ANT being non-living (or non-human, or whatever term they choose to use) is to re-define the meaning of "living":"Fully constituted, the organism is a self-sustaining and harmonious whole, a unified being with an inherent principle of organization that orders and guides its continuity of growth. In the human embryo, this principle of organismal unity is an engaged and effective potential-in-process, an activated dynamic of development in the direction of the mature human form." Again, unaltered, the embryo would progress along the natural developmental path; altered, the embryo is denied that natural development.

This rationalization is crudely analagous to genetically altering the hypothalamus or androgen/LH receptor genes of a child, inhibiting that child from progressing through puberty into adulthood, and then claiming that, because the child is unable to progress along his natural developmental path, that he is not "living".

Remember, the somatic cell is inherently capable of development into a fully developed entity. This concept is the entire basis of SCNT. Thus, the somatic cell is in no way materials that are incapable of being an organism, nor is it like "corpse with still-living material.

The moral and ethical concerns of genetically altering a potential human life are myriad, and better left for another day. My point here is only to clarify the process of ANT and the nature of the entities involved beforehand and produced as a result.

Finally, Parableman's comment:

...I think it's misleading to describe it as a living embryo and then preventing it from growing.

The embryo resulting from SCNT inherently progresses along its natural development path. The embryo resulting from ANT begins progressing along that same natural development path, but has been genetically inhibited from completing that path. It reaches at least the blastocyst stage - as evidenced by its development of embryonic stem cells.

ANT does not directly produce stem cells; it produces an embryo that develops stem cells as part of its natural developmenet process. Again, argue the moral/ethical issues surrounding the creation of an embryo genetically altered to inhibit its development; but the claim that ANT does not produce a human embryo is unequivocally untrue.