Friday, February 09, 2007

Stem Cells Part VI: Cloning.

We have covered a lot of material in the first few essays, on stem cells in general and human embryonic stem cells (hES cells) in particular. We've looked in some detail at how hES cells are obtained in the laboratory, and seen that the process involves the destruction of a human embryo. It is this destruction of the embryo at the blastocyst stage to obtain its inner cell mass - those cells which will give rise to in vitro hES cells - which is the source of the immorality of the procedure[1]. We have also seen that a fully developed and mature hES cell research and development program such as that desired by the majority of our elite will require the production of human-animal chimeras,[2] a process which is immoral prima facie. Now we will look at another immorality which is a necessary component of our hypothetical mature hES cell R&D program: cloning of human embryos via somatic cell nuclear transfer (SCNT). We'll begin with some definitions.

Somatic cell: Any cell of a plant or animal other than a germ cell or germ cell precursor.[3]
Germ cell: A sperm or egg or a cell that can become a sperm or egg. All other body cells are called somatic cells.[4]
Somatic cell nuclear transfer: The transfer of a cell nucleus from a somatic cell into an egg from which the nucleus has been removed.[5]

The human genome has 46 chromosomes, but a germ cell has only half that number, 23. That is because the father's germ cell, his sperm, will contribute half of his genetic makeup to the new baby, and the mother's germ cell, her oocyte, will contribute her half. Upon conception, mom's 23 chromosomes and dad's 23 chromosomes combine to form a new, genetically distinct individual with 46 chromosomes. This new individual starts out, as we all did, as a single celled zygote, but soon divides and divides again to form, eventually, a grownup person. From conception until death, every cell a person forms will be a somatic cell[6], with a complete copy of the 46 chromosomes inherited from mommy and daddy that fateful day long ago up in mom's fallopian tube. Even though all somatic cells have a complete copy of the genome, in any given cell, for example, a liver cell, the majority of the genome is turned off, and only those parts necessary for the cell to function as a liver cell are turned on. However, in theory, if one could properly activate the genome of that liver cell, one could manufacture a complete new human being, a genetic copy of the human from whom the original liver cell came. Nice theory. How might it be accomplished in practice?

The oocyte has some interesting characteristics. In addition to being a germ cell, the egg is much, much larger than the sperm. This is because the oocyte contains, in addition to mom's half of the genetic contribution, all the molecular machinery necessary to activate the newly formed genome. This molecular machinery is contained within the egg's cytoplasm, the part of the egg which is not the nucleus. Thus, when a new genome appears within the oocyte - such as at conception - the oocyte's cyoplasmic machinery fires up, unzips the new genome, and starts it on its way. SCNT takes advantage of this capability of the oocyte. First, the nucleus is first removed from an oocyte such as, for example, the oocyte of a Scottish blackface ewe. Then, the nucleus containing the genome of a somatic cell from somewhere else, say the mammary gland of a 6 year old Finn Dorset ewe, is transferred to the enucleated oocyte. Hence the name, somatic cell nuclear transfer. That new combination of Finn Dorset ewe mammary gland nucleus and Scottish blackface sheep oocyte cytoplasm will form a new embryo which has the genome of the original Finn Dorset ewe. If implanted in the uterus of a sheep, this embryo might grow to live birth. That is how Dolly the Finn Dorset sheep was cloned, and gestated to birth in the womb of a Scottish blackface sheep, ten years ago, back in 1997[7]. A similar technique was reported for the efficient cloning of human embryos by the South Korean researcher WS Hwang in the world renowned journal Science in 2004.[8] A second paper came out in Science in 2005;[9] both were heralded by the world's lay, political, and scientific organs as great breakthroughs in hES cell research, because cloned human embryos could now be produced reliably in large quantities. Dr. Hwang became an instant celebrity on the stage of the world. Sadly, the research turned out to be fake, and Science had to retract the articles[10].

The process of using SCNT to produce a cloned embryo which is then implanted in a womb and gestated to birth has come to be known as "reproductive cloning"[11]. If, instead if implantation, the cloned embryo is destroyed to obtain its inner cell mass for the purpose of generating embryonic stem cells, the process is commonly known as "therapeutic cloning"[12]. It has been pointed out this latter term is misleading as it implies that therapies derived from hES cells are a reality[13], when such therapies exist only as fiction. But the name has stuck, so we shall use it. The point is this: there is not an iota of difference between the embryo produced by therapeutic cloning and the embryo produced by reproductive cloning. The only difference is what is done with the cloned embryo: destroyed for its inner cell mass, or implanted in the hopes of producing a liveborn. In the case of the cloned human embryo, whether it has a soul is known only to God.

Next week: why cloning is so necessary in hES cell research.

[1] This is not to say that other activities associated with hES cell research are without moral problems. For example, in vitro fertilization, the source of many cast-off blastocysts, is in itself immoral. However, we are confining ourselves here to hES cell research only.
[2] "Guidelines for Human Embryonic Stem Cell Research." National Research Council and Institute of Medicine of the National Academies National Academy Press, Washington, D.C. 2005. See Ch. 2, "Scientific background", pg. 31.
[3] Guidelines, ibid, Glossary.
[4] ibid.
[5] ibid.
[6] This is not strictly true, for the new person will also have her own set of germ cells, but that doesn't concern us here.
[7] Wilmut I, Schnieke AE, McWhir J, Kind AJ & Campbell KHS. Viable offspring derived from fetal and adult mammalian cells. Nature 385 (6619):810-813, 7 Feb 1997.
[8] Hwang, WS, Ryu, YJ, Park, JH et al. Evidence of a pluripotent embryonic stem cell line derived from a cloned blastocyst. Science. 2004; 303:1669-1674.
[9] Hwang, WS, Roh SI, Lee BC et al. Patient-specific embryonic stem cell line derived from a cloned blastocyst. Science. 2005; 308(5729):1777-1783.
[10] Science 311(5759):335. 20 Jan 2006.
[11] Hipp, J & Atala, A. Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy. Journal of Experimental & Clinical Assisted Reproduction 2004,1:3; 8 Dec 2004.
[12] ibid.
[13] de Wert G & Mummery, C. Human embryonic stem cells: research, ethics and policy. Human Reproduction 18(4):672-682, 2003.


Sharon said...

I'm probably being dumb here but I can only find parts 1, 5 and 6 for this topic. Could you please point me to where the other parts are.

kat said...

Yes, I know. I'm trying to get them organized by topic on the right, as well as linked by the little "Topics" button at the bottom of the essay.