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Human Embryonic Stem Cell Research

  1. Introduction

    Human embryonic stem cell (hESC) research is thought to have great potential in disorders in which cellular loss is known to occur. These include Type 1 diabetes mellitus, Parkinson's disease, and the post-myocardial infarction heart. Nevertheless, some believe that pre-implantation embryos are potential human beings with a soul making hESC research immoral. Human embryonic stem cell research raises other important ethical dilemmas as well. As a result of these ethical and moral dilemmas the government has limited federally funding for hESC research to what has turned out to be 19 pre-existing "registered" cell lines (Sept. 2005. Private sources and states have been left to determine the extent to which they are prepared to support additional hESC research. A number of states, most prominently California, have decided to support research in this area.

  2. What are embryonic stem cells and how do you make them?

    The goal is to have stem cell lines derived from embryonic stem cells. Cells from these lines are "totipotential" because in theory, they can be transformed into any kind of tissue by the appropriate biological and chemical manipulations. Without going into detail and elaborating on all the limitations and caveats, embryonic stem cell lines can be created three ways.

    1. Eggs and sperm can be obtained from donors, mixed in a Petri dish and the egg fertilized for the purpose of producing a stem cell line for research. The fertilized egg (zygote) divides into a multicellular embryo. With further incubation a blastocyst, a hollow ball of about 256 cells, is formed. The blastocyst has two kinds of cell groups, a group on the surface that is capable of initiating implantation into the uterus and becoming the placenta, and the inner cell mass with the capacity to become the fetus. The inner cell mass can be removed and encouraged to divide in culture medium. Under carefully defined conditions, these can be induced to become a cell line, dividing indefinitely. With proper chemical treatment the stem cells can, in theory develop into any tissue.

    2. Annually, many thousands of infertile couples create embryos for in-vitro fertilization (IVF), by having their eggs and sperm mixed and fertilized in a petri dish. Usually the potential mother is stimulated with hormones and provides a number of eggs. Similarly, the potential father has millions of sperm in his ejaculated semen. Normally all the eggs are exposed to sperm and a number of become fertilized and become embryos. The best looking embryos are incubated long enough to become blastocysts. Usually three are implanted into the potential mother's uterus. The remaining embryos are stored in liquid nitrogen in case of pregnancy failure or for later use if the family wants another child. These embryos are stored in cryobanks. Many of them eventually become available for research. With informed donor consent from both parents, these frozen embryos have the potential for providing most of the necessary raw material for stem cell research.

    3. Somatic cell nuclear transfer (SCNT or just NT) was responsible for creating the sheep clone Dolly. In this process, young women donate ova by undergoing the "superovulation" process, as do infertile women. The egg has its nucleus containing the genetic material removed. The nucleus of an adult cell of research interest is placed into the enucleated egg. By a remarkable process the adult nucleus dedifferentiates in the ovum from, say a skin cell, into a totipotential state and the ovum proceeds to divide and become a blastocyst. Its inner cell mass can be made into a stem cell line. This process has a theoretical advantage in that theoretically stem cells could be produced with any genetic condition of interest by introducing the nucleus from a person with the condition. The major disadvantage of NT is that a supply of human unfertilized eggs is required to do the research. Until a reliable source of human ova can be obtained without either a large payoff or by coercion, this process is unlikely to become the main source of embryonic stem cells. However, it is conceivable that mothers of individuals with a serious disorder such as Type 1 diabetes mellitus would be willing to donate eggs to further research progress.

      A major ethical dilemma that has just grounded the highly successful Korean Stem Cell Institute was the provision of ova by laboratory workers who had a dependent relationship to the investigators and were therefore susceptible to coercion.

  3. Ethical Issues

    1. The core issue related to hESC research is the status of the early embryo. Is it a human being with a soul that must be protected or is it a collection of cells that will not become part of humanity until a later time. This issue cannot be resolved on a scientific basis but rather plays a central role in religious and political differences within America.

    2. Unlike the use of zygotes containing the combined genetic material from a male and a female, as in IVF, NT results in a "clone" of the donor of the adult cell. Implanting such a blastocyst into a woman, termed "reproductive cloning," would result in an individual with the exact genetic makeup of the donor of the nucleus. Agreement has been reached that reproductive cloning of humans is unethical and should not be permitted.

    3. NT, which to date is a very inefficient process, requires large numbers of donated ova from volunteers. In other research settings, volunteers may be paid for their trouble but must not be coerced into volunteering either by being dependent on the investigators or by enticing them with compensation. These same criteria are likely to hold for ovum donors although ovum donors for the treament of infertility are being paid large amounts of money for their efforts.

    4. Ovum donation is not a benign procedure. A sample consent form for ovum donation for hESC research purposes is given below.

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