The ethical challenge of stem cell research and tissue transplantation

- Saeideh Ziaei*(MD),Mohsen Farokhi(LLM)
Department of Obstetrics & Gynecology
Tarbiat Modarres University, P.O.Box 14115-111 Tehran Iran
Email: ziaei_99@yahoo.com

Eubios Journal of Asian and International Bioethics 14 (2004), 97-99.

Abstract
The use of human embryonic stem cell to replace damaged cells and tissues promises future hope for the treatment of many diseases. However,many countries now face complex ethical and legal questions as a result of the research needed to develop these cell-replacement therapies. This study design to explore attitudes of Shia religious lawyers, jurisprudists,and scientists to different techniques of derivation of stem cell. Twenty six participants were asked about their attitudes and concerns to embryos surplus IVF, embryo creation through therapeutic cloning and the embryos destruction. Ultimately, attitudinal responses were collected and considered. The majority of respondents indicated that: the preimplantation embryos have not human rights exactly; the importance of not wasting surplus IVF embryos and permission to destruction of these embryos for stem cell research and tissue transplantation; and permission to creation embryos through therapeutic cloning for stem cell research and tissue transplantation. Restrictions on research on stem cell are questionable as they inhibit the development of a technique which holds promise for successful application of pluripotent stem cells in clinical treatment of severe diseases.
Key words: Ethics/human embryo/legal/Shia religious/stem cell research/transplantation

Introduction
Embryonic stem (ES)-cell research offers the hope of cell-replacement therapy for many diseases; however, formidable scientific and clinical challenges must be overcome before such therapies could become available.1,2 Scientists need to learn how to direct pluripotent ES-cells to differentiate into the required cell or tissue type. 3 Also, clinicians must determine the transplanted cell's immune compatibility with the host, and where, and in what amounts, to replace cells in diseased organs to achieve a therapeutic effect. Transplanted ES-cells spontaneously differentiate into any of a variety of ectodermal, endodermal and mesodermal cell types-sometimes into a disorganized mass of neurons, cartilage and muscle; sometimes into teratomas containing an eye, hair or even teeth. 4 Progress has been slow, but some success has already been achieved in directing the development of stem cells into specific lineages. For example, the vitamin A derivative, retinoic acid, has been shown to turn ES-cells into neurons. Many of these differentiated cell types could be useful in medicine as individual or small groups of cell. Although there is still the task of putting the cells together to create or recreate functional structures.
These scientific efforts are also complicated by ethical concerns about obtaining human ES-cells from early embryos. The resulting controversy has delayed or stopped human ES-cell research in some countries, and could affect the extent to which human ES-cell derived therapies are developed and used.
This study aimed to explore attitudes and concerns of Shia religious lawyers. Jurisprudists, and scientists to ES cell research and its production through cloning method and ES-cell harvest from surplus in vitro fertilization (IVF) embryo.

Materials and methods
Three kinds of questionnaires; one for jurisprudists; one for religious lawyers; and one for religious scientists who were affiliated in an Assistant Reproductive Technology (ART) lab, were prepared. The content of all the questionnaires were similar, but the questions were asked in three different ways for better orientation. All participants were asked about their attitudes and concerns to embryos surplus IVF and its donation, embryo creation through therapeutic cloning and its donation and embryo destruction. Ultimately, attitudinal responses were recorded and all comments reflecting a positive or negative orientation to embryo donation and destruction for medical research and ES-cell therapies were collected and considered.
All participants have religious affiliation to the practice of their "Shia" religion conservatively. Shia is a branch of Islam and majority of Iranians are Shia.

Results
Attitudes to embryos regarding whether respondents thoughts of embryos as potential human, creation embryos for ES-cell production, destruction of human embryos to obtain ES-cells for research, using surplus IVF embryo for ES-cell production are summarized in Table I.
Table I: Attitudes to the embryos, its creation, its donation, and its destruction.
Numbers across the page are Yes/No for Three Samples: Scientists (n:15); Jurisprudists(n:6); Lawyers (n:5)

Inclined to think of surplus IVF embryo as a human 2/ 13; 3/ 3; 1/ 4

Permission to destruction of surplus IVF embryo 14/ 1; 5/ 1; 4/ 1

Inclined to think of embryo creating from therapeutic cloning as a human 1/ 14; 2/ 4; 1/ 4

Permission to destruction of embryo creating from therapeutic cloning 14/ 1; 5/ 1; 4/ 1

Permission to creation embryos through therapeutic cloning 14/ 1; 5/ 1; 4/ 1

In this study, additional views on embryo creation, embryo donation, embryo destruction for medical research or cell-replacement therapy were recorded at the end of questionnaires entitled as free comments. The comments reflected both positive and negative orientations. There were four themes underpinning a positive attitude: The importance of not wasting human embryos; the explicit desire to help patients; the preimplantation human embryos have not human rights exactly; and embryos created by nuclear-tranfer cloning technique have not the same human rights as embryos produced by human oocytes fertilized by human sperms.
The themes underpinned a negative attitude were: an explicit view of the surplus IVF embryos as potential children; a view that other options (e.g., using adult stem cell) were preferable; and worry about what sort of research would be done with embryos.
Discussion
Legal treatment of the use of human fetal tissue or the destruction of human embryos to obtain ES-cell for research varies widely throughout the world. The United States, England and many other countries permit the use of human fetal tissue for research when a woman's decision to donate fetal tissue is clearly separated from the decision to abort5,6,7,8. When stem cells are obtained from preimplantation human embryos, ethic objections arise from the need to destroy embryos to obtain these cells. Those who believe that preimplantation human embryos are themselves persons or subjects with rights, are against the destruction of embryos for research. In this study the majority of respondents believe that the preimplantation embryo is too rudimentary in development to have human rights. Hence, generally permit ES-cell research.
The neural development that is essential to have inherent moral status and interests in one's right is not present in the undifferentiated cells of preimplantation embryos. The earliest differentiation in the embryo is towards trophoblastic tissue, after which the inner cell mass forms-it is from these cell that the embryo properly develops and from which ES-cells are derived9.Only after implantation in the uterus does the embryo properly being to establish its body plan, events that are later followed by the development of the nervous system. Denial of the early embryo's inherent moral status; however, does not mean that the human embryo is perceived as being without value. The rejection of the view that the embryo is a person, does not mean that the embryo is similar to ordinary human tissue because of the unique potential it has to develop into a new human being. Some of the respondents described embryos as having special respect. This attitude towards human embryos symbolizes our respect for human life generally.
In the context of IVF treatment, the generation of more embryos than can be safely transferred to the uterus is common. Some of these surplus IVF embryos can be freeze for subsequent treatment for the couple or for other infertile couples. But many of them are left and wasted right now. Obtaining human ES-cells from these embryos for the goal of treating diseases and saving lives justifies the symbolic loss that arises from destroying embryos in the process. In this study the majority of respondents emphasized on the significance of saving life of many patients who need cell replacement therapy, as an essential reason for permission of research on embryos and obtaining ES-cells from them.
A different set of ethical issues arises once researchers have learnt safe and effective ways to direct human ES-cell to differentiate into specified cell or tissue types, and to transplant them for therapeutic effects in patients. An important clinical issue at this point will be whether ES-cell not derived from the patient, will be rejected by the patient's immune system. If so, one strategy for dealing with this problem, would be to use a patient's nuclear DNA to create an embryo from which ES-cells compatible with that patient could then be derived 10,11,12. If nuclear-transfer cloning were necessary for safe and effective use of ES-cell derived replacement therapies, three additional ethical issues beyond the destruction of left-over embryos to obtain human ES-cells, would arise.
One issue would be ethical concerns about creating human embryos for the sole purpose of destroying them to obtain replacement cells for the patient who provided the nuclear DNA. Ethical debates about creating human embryos solely for research have existed since the inception of debates over embryo research 13. One can question; however, whether those concerns are even relevant to generating human ES-cells by somatic cell nuclear transfer, for the haplogenomes of gametes are not combined through sexual fertilization to form the blastocyst that provides the ES-cells. In addition, there is no intention of culturing the embryo beyond the blastocysts stage, nor of implanting that blastocyst in a uterus for reproduction. Given the asexual means of creating the embryo and the lack of intent of implanting it in the uterus, the embryonic entity produced in these circumstances lacks the reproductive significance that some have argued is the moral basis for valuing early embryos 10,14. If one rejects the view that embryos have interests or are the subjects of moral duties, then creating them for research or for therapeutic purposes does not further substantive harm to them. Furthermore, it is argued that potential therapeutic benefits of the procedure far outweigh the harm. The morality in letting millions of people continue to suffer from chronic and life threatening diseases is under question. In this research many respondents accepted the significance of the above mentioned issues.
A second ethical issue that would arise if therapeutic cloning became necessary for effective cell-replacement therapy would be the scarcity of human oocytes with which to dedifferentiate a patient's somatic cells to stem-cell types (which could then be multiplied for therapeutic purposes). The ability to meet the therapeutic demand for oocytes would present an important problem. The ability of live, unrelated donors to meet such a demand is highly unlikely for several reasons: the hormone treatments that stimulate the production of many oocytes imposes a considerable burden on women; surgery is required to retrieve the oocytes; and ethical problems now surround such donations 15. Alternative sources of human eggs might be cadavers or aborted fetuses. Techniques to mature oocytes in vitro so that they could receive transferred nuclei would wave to be developed, but little research to perfect such techniques is occurring. If it becomes possible to mature oocytes in vitro, other ethical issues concerning the use of cadaveric or fetal ovary donations would then have to be faced, such as the risk of non-consensual posthumous reproduction by the cadaveric or fetal donor. A third alternative to meet the demand for oocytes would be to use bovin eggs, which are in plentiful supply from slaughter houses 16. Viewed solely as a way to get the nucleus to express it self to the blastocyst stage, with no transfer to the uterus permitted, bovin eggs might be an ethically acceptable way to supply the oocytes needed to provide many patients with immunologically component replacement cells.
In summary, in this study, three important reasons that were presented for the permission of research on embryos were: 1) restriction of research on preimplanted embryos are questionable as they inhibit the development of a technique which holds promise for successful application of pluripotent stem cells in clinical treatment of severe diseases; 2) an embryo before implantation does not have human rights similar to a fetus or children; 3) there is no intention of culturing the embryo created by cloning beyond the blastocysts stage and implanting them in a uterus for reproduction.

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