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October 2003

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Cloning stem cells - change on the horizon

Dr Ames Dhai

Research into stem cells from human embryos raises a number of ethical and legal issues. On the one hand, the medical profession and the public grapple with the promise that important knowledge could benefit society at large. On the other hand, the moral complexities require consideration - not only the why and how, but also whether there are compelling reasons to limit or prohibit research in this field entirely.

The ethical debate - an overview

There have been mixed reactions to the prospect of cloning for biomedical research. Supported by some for its medical promise, it is opposed by others who view it as intentional exploitation and destruction of nascent human life created specifically for research purposes. Human dignity would in this way be undermined. Debated also is the issue of proceeding with research that is considered fraught with moral uncertainty. Other anxieties: the possibility that women (as donors of eggs) would be exploited; the slippery slope towards reproductive cloning; and promises made too early creating false hope among sick patients.

Chronic debilitating degenerative diseases including those of the brain (Parkinson's and Alzheimer's Disease), pancreas (diabetes), liver (hepatitis), joints (rheumatoid arthritis) heart, lungs and kidneys and spinal cord injuries cause immense suffering to patients, their families and society. Embryonic stem cell research may offer unique ways of investigating and possibly treating many of these diseases.

Moreover, embryonic stem cells could benefit patients requiring transplants. Organs and tissues created from nuclear transfer utilising recipient nuclei (for example, a patient with kidney disease could grow his or her own replacement organ) hypothetically would survive the expected normal immune rejection, in which the patient's body rejects the new organ as a foreign object. The possible medical gains of embryonic stem cell research are immense.

Cloning and the law

The laws governing genetic manipulation are - in South Africa, at any rate - about to change. In South Africa, neither reproductive nor therapeutic cloning is allowed but the National Health Bill is due to be passed before parliament closes at the end of 2003, and many things will change when this bill becomes law.

Embryo stem cell research and therapeutic cloning will not be legislated against. Reproductive cloning remains off limits. Very strict regulatory criteria will have to be fulfilled for therapeutic cloning, including authorization by the Minister of Health for work in this field. Section 62(4) affirms that the Minister may permit research on stem cells and zygotes that are not more than 14 days old. Public participation in this process has been in effect since August 2002 when the bill appeared in the Government Gazette and there were advertisements in national print media soliciting presentations for the discussions at the parliamentary portfolio committee of health.

The Medical Research Council in South Africa recommends that for the present, fetal tissue from cadavers and embryos remaining after completion of infertility treatments should be the only source of embryonic stem cells for the purposes of research. But these recommendations are too restrictive and may stifle scientific progress whose objective is to benefit patients with irreversible and debilitating disease.

What are Stem Cells?

Stem cells are tissue precursor cells that have the ability to self-renew and differentiate into more specific cell types. They are important because they can replace dying, old or damaged cells. These cells are found in human embryos, fetuses, children and adults, i.e. at all stages of development and in most tissues but it is the embryonic cells which have raised the most controversy.

Early human embryos (5 - 6 day old blastocysts) have an outer cell layer from which the placenta develops, and an inner cell mass, in the region of 200 cells, which gives rise to the fetus. This inner cell mass is the source of embryonic stem cells.

Deriving embryonic stem cells

                Deriving embryonic stem cells

We need to distinguish between two fundamental types of embryonic stem
cells. Totipotent stem cells are found in the 16-cell stage embryo. These
cells have the ability to form an entirely independent human being if placed
in the uterus. Because of the potential of totipotent cells and the resultant ethical dilemmas, scientists have, in the main, avoided research on this type of stem cells.

On the other hand, the inner cell mass of the late blastocyst stage of the embryo comprise pluripotent stem cells which have a limited ability to give rise to any type of specialised cell. Pluripotent stem cells are being considered for therapeutic work, combating debilitating diseases and finding new drug treatments for diseases. (In addition, in the adult, somatic stem cells are more committed or multipotent. This means that their differentiation is restricted to only one or a few tissue lineages. There is still much research being done on these cells.)

Potential sources of stem cells are:

  • fetal tissue that becomes available after an abortion
  • excess embryos from assisted reproductive technologies such as commonly used in fertility clinics
  • embryos created through in vitro fertilization specifically for research purpose, and
  • embryos created asexually as a result of the transfer of a human somatic cell nucleus to an egg with its own nucleus removed.

Other sources of stem cells are those from umbilical cord blood, and bone marrow. In addition, neural stem cells, haematopoetic stem cells and mesenchymal stem cells can be harvested from fetal blood and fetal tissue.

Cloning

Strictly speaking, "clone" means a precise genetic copy of a life form. The proposed National Health Bill of the Republic of South Africa defines therapeutic cloning as the manipulation of genetic material from either adult, zygote or embryonic cells in order to alter the function of cells or tissues. Cloning at a molecular level involves the copying of DNA fragments containing genes and amplifying these in a host cell. The copying of somatic cells through growing in culture results in cellular cloning. This type of cloning could be used for the testing and production of new drugs. For example, if high cholesterol is found to have a specific gene defect, we can with therapeutic cloning allowed then clone the cell and test drugs on the defective gene.

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Glossary

Stem cells: A cell that can replicate indefinitely and which can differentiate into other cells; stem cells serve as a continuous source of new cells. Specifically, this refers to the self-regenerating cells in bone marrow and the testis.

Totipotent stem cells: Stem cells which are capable of forming every type of body cell. Each totipotent cell could replicate and differentiate and become a human being. All cells within the early embryo are totipotent up until the 16 cell stage or so.

Pluripotent stem cells: Pluripotent stem cells can eventually specialize in any bodily tissue, but they cannot themselves develop into a human being.

Somatic Cells: Cells from the body that compose the tissues, organs, and parts of that individual other than the germ (sex) cells. Each somatic cell contains a full set of chromosomes, whereas sex cells only contain half.

Zygote: An egg cell that comes from fertilization. It contains the complete set of chromosomes received from the union of the male (sperm) and female (egg) sex cells. The zygote develops into the organisms adult body.


More information

1. The President's Council on Bioethics. Human Cloning and Human Dignity: An Ethical Inquiry. Washington DC July 2002; 80-110.  www.bioethics.gov 
2. The Advisory Committee on Health Research. Genomics and World Health. World Health Organisation Geneva 2002; 107-173.
3. Fisk NM, Braude P. Stem Cells. The Obstetrician and Gynaecologist 2001: 3 :211-212.
4. Holm S. Going to the Roots of the Stem Cell Controversy. Bioethics 2002; 16:493-507.
5. Lochner JdeV. The Ethics of Research on Stem Cells of Human Origion. SAMJ 2002; 8:54-57.
6. Office of News and Public Affairs, UW Madison. Stem Cell Pres Kit, 1998. http://www.news.wisc.edu/emediakit/fact.html
7. Varmus H. Statement of Harold Varmus, Director, National Institutes of Health, before the Senate Appropriations Subcommittee on Labor, Health and Human Services, Education and Related Agencies, 26 January, 1999. http://www.hhs.gov/progorg/asl/testify/t990126a.html
8. National Bioethics Advisory Commission. Ethical Issues in Human Stem Cell Research - Executive Summary, September1999.
9. Campagnoli C, Fisk N, Overton T, Bennet P, Watts T, Roberts I. Circulating haematopoetic progenitor cells in the first trimester fetal blood. Blood 2000: 95 : 1967-72.
10. Medical Research Council South Africa. Reproductive Biology and Genetic Research. Guidelines on Ethics for Medical Research;2:36-50.
11. National Bioethics Advisory Commission. Cloning Human Beings - Report and Recommendations of t he National Bioethics Advisory Commission, 1997.
12. The National Health Bill, Republic of South Africa. Government Gazette No. 23696 of 8 August 2002. [B 32- 2003]. Section 62
13. Solter D, Gearhart J. Putting stem cells to work. Science 1999: 283: 1468-70.
The Human Tissue Act No. 65 of 1983. Section 39A.

Public Understanding of Biotechnology website www.pub.ac.za


Public Understanding of Biotechnology                                                  Department of science and technology, South Africa.


 

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