Stem Cells

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Ethical issues of stem cell therapy as a medical treatment
Nur Tiara Binti Hassan SES 100247 Profesor Dr. Norzulaani Binti Khalid

The use of human embryo for research on embryonic stem (ES) as a medical treatment is currently high on the political and ethical agenda in many countries including Malaysia. Human embryonic stem cell has generated much interest in public debate and is not only discussed by biologist but also by medical profession, governments, politicians, media and ethicists. The use of human embryonic stem cell remains controversial despite its potential benefits because of the derivation from early embryos (human pre-implantation embryos). In Malaysia, although they are many controversies surrounding stem cell research, The Ministry of health (MOH) recognises that is important for local clinicians and scientist to be involved in stem cell research provided that they abide to the ethical guideline (Malaysia Medical Council, 2002/2009). It is crucial to keep up with the current advances in science, especially when there is a huge potential of revolutionising therapy in the form of cell replacement therapy. Stem cell therapy is believed to represent the future cure or relief of a wide range of common disabilities. As science and technology continue to advance, so do ethical viewpoints that surround these developments. Before we proceed with the discussion on ethical issues, we will first discuss the properties of stem cells and its potential use. What are stem cells? Stem cells are undifferentiated cells found in the human body that have a remarkable potential to develop into many different cell types that carry out different functions. In other words, they are built to function in a particular organ system and carry out a specific function. The specialized of differentiated cells result from the process of cell division. When a stem cell divides, each new cell that arise has the potential to become another type of cell with more specialized function such as the muscle, brain and blood cell or remain a stem cell. Serving as a sort of repair mechanism for the body, they can theoretically divide without limit to replenish other cells as long as the host (in our case human) is still alive. They are generally two types of stem cells: embryonic stem (ES) and adult stem cell which is also known as somatic stem cell. The first embryonic stem cells were derived from mouse embryos in 1981. Embryonic cells can only be derived from pre-implantation embryos and are proven to have the ability to form all the different type of cells found in the human body as diverse as those found in the bone, heart, brain and skin. This ability can be termed as ‘pluripotent’ where cells can develop into many different cell types of the body. They are derived from the inner cell mass of blastocyst that develops in culture within 5 days of oocyte fertilization. To date, most embryos used for the establishment of Human embryonic stem cell lines (hES) are derived primarily from blastocysts that were created by in vitro fertilization (IVF) for assisted reproduction but were no longer needed (spare embryos) ( International society for stem cell research, 2011). Human embryonic stem cells (hESC) can also be obtained by therapeutic cloning or somatic cell nuclear transfer (SCNT)

Adult stem cells on the other hand, are a more specialized cell and can produce some or all of the mature cell types found within the particular organ or tissues in which they reside. The may remain undivided (quiescent) for many years until they are activated by tissue injuries or disease. Due to its ability to generate multi organ-specific, cell types, they are termed as ‘multipotent’. Adult stem cells have a more limited capacity and they represent a very small population in each tissue. For example, a multipotent stem cell in the bone marrow can develop into a white blood cell or a red blood cell, but not into a brain cell or skin cell. The research on adult stem cells began in the year 1960s, where researchers found that the bone marrow contains at least two kinds of stem cells which are the hematopoietic stem cells and bone marrow stromal cells. Stromal cells are a mixed cell population that produces bone, cartilage, fibrous connective tissue and fat. It has been reported that adult tissues which contain stem cells include bone marrow, skeletal muscle, blood vessels, brain, liver and skin ( International society for stem cell research, 2011) Another type of stem cell that is currently being talk about in stem cell research community is the iPS cells (induced pluripotent stem cells). This technique has been developed since 2006 (Malaysia Medical Council, 2002/2009). iPS cells are adult cells that are ‘reprogrammed’ to become pluripotent. iPS cells were originally produced by using virus as a vector to insert extra copies of three to four genes for example Oct4, Sox2,c-Myc and Klf4 which are known to be important in ES into specialized cell. Oct-4 gene for example, is a transcription factor, that turn genes on and off at the right time. They play an important part in cell differentiation and embryonic development( International society for stem cell research, 2011). iPS cells are able to make pluripotent stem cell lines that are specific to an individual patient and disease. Patient-specific stem cells are generated form the patient itself. It holds an advantage to minimise some of the serious complication of histocompatibility and rejection that may occur during transplants from unrelated donors. Disease-specific stems cell have already become a very useful tool in drug development. Stem cell has enormous potential usage. The major important potential use of hESC is in transplantation medicine. In this therapy, hESCs are coaxed to form a plethora of differentiated cell types. These derivatives of cell types can be used to develop cellreplacement therapies for various human diseases. The prime candidates for hESC replacement are Type 1 diabetes and Parkinson’s disease. For patients who suffer from Type 1 diabetes, the cells of the pancreas that usually produce insulin are destroyed by the patient’s own immune system. Recent studies showed that it may be possible to direct the differentiated, hESC in cell culture to form insulin-producing cells that could eventually be used in transplantation treatments for diabetics. Parkinson's disease (PD) is a very common neurodegenerative disorder. To date, it has affected more than 2% of the population that are over 65 years of age. Parkinson's disease are generally caused by the progressive degeneration and loss of dopamine (DA)-producing neurons which leads to abnormally decreased mobility. Currently, scientists are developing a number of strategies to produce dopamine form human stem cells in the laboratory for transplantation into humans with Parkinson's disease.

Despite the major potential benefit of stem cell in medical therapy, they receive many ethical, political and religious debates. Much of the debates surround human embryonic stem cell research because it is closely linked to the destruction of human embryos and the effort to clone human being for medical purposes. Many public speculate that the religious community most commonly the Catholic Church is against all human stem cells research. However, this is inaccurate as they only oppose any research that undermines the dignity of human being. Certainly they would support all ethically accepted research that aims to alleviate the health of human kind if the cells could be obtained without destroying the human embryos. Many debate focused on the question of when a human embryo attains personhood, whether human embryo should be treated as a person, should we use research methods that destroy human embryos to search for new therapies that could help people in the future and where should the embryos for stem cell research come from. Proponents of destructive human embryo research often argue that human life does not begin at conception. They agree that embryo research is morally acceptable for specific purposes if it is limited to the fourteen days following fertilization and provided that no embryo which is subjected to research is re-implanted in the uterus. Once embryo is not implanted, they no longer have a future. The also argues that human embryo are not human being because they lack emotional, spiritual, and physical aspect hence does not have privilege to claim any right that includes the right to life. In reproductive technology, many donated embryo are destroyed to achieve a successful goal of pregnancy. Proponent argues that if the remaining embryo which is unsuitable or intended to be discarded, its use for deriving Embryonic Stem cell will not alter it finals disposition. Embryo could alternatively be made through in vitro fertilisation (IVF) from donated gametes to produce cell lines Opponents argue that there is no real preembryo-embryo distinction and that the human life begins at conception. This is proved scientifically through the cloning technology. The human embryo is a unique human being from the moment of conception. They are unique because during fertilization they bring together a unique combination of 46 chromosomes from both parents. This unique and distinctive combination of genes distinguishes the embryo from any other cells. ‘From the time that the ovum is fertilized, a life is begun which is neither that of the father nor of the mother, it is rather the life of a new human being with his own growth. It would never be made human if it were not human already’ [Declaration on Procured Abortion, November 18, 1974, nos. 12-13]. Individuality is defined by the presence of body axes that coordinates system and provides a blueprint for the organism’s body plan. Recent experimental works were done in the UK to shows that the embryonic axes are already present in the one celled mammalian zygote. This further justify that human life begins from the moment of conception. .

The white paper written by the Bioethics Council provides an alternative source of human pluripotent stem cells. This alternative allow scientist to harvest pluripotent stem cells without destroying human embryos. One of the most accepted proposals was obtaining pluripotent human stem cells from reprogrammed differentiated cells taken from the adult human. Two research team, which is one from Japan and the other in the US, had successfully reprogrammed adult human cells into pluripotent stem cells. These cells are called induced pluripotent stem (iPC) cells. Two weeks later, a team from M.I.T had successfully cure sickle-cell anemia in mice which further proof that this technology could be used for regenerative medicine. There are also heated issue on stem cell research because of its relation to human cloning. There are basically two types of cloning which is the therapeutic and also reproductive cloning. In reproductive cloning, embryo will be formed by transplanting the DNA of the adult cell into a female egg whose nucleus already being removed. Proponents stand on the point that reproductive cloning is for the benefit of infertile female of couple that intend to have a child, hence the close link to IVF procedures. On the other hand, therapeutic cloning is done by creating a clone of the adult through somatic cell transfer in order to stave off personal disease or illness. To sum up, both cloning begins with the same procedure. The only thing that differs between these two procedures is that the goal of reproductive cloning is to produce offspring while for therapeutic cloning is to produce embryonic stem cells for treatment and or research. The science of cloning is still in its early stages and some scientists believe that today’s technology just isn’t ready to be tested on humans. The embryos are either died some time during gestation or shortly after birth or simply not suitable for implanting into the uterus. Nearly 98 % of cloning trials end in failure (Kolata, 2001). With this very high rate of failure, it would be very inhumane to attempt this technique to human being. Even Ian Wilmut, one of Dolly’s co-creators, opposed human cloning. He stated: "We think it would be ethically unacceptable and certainly would not want to be involved in that project." Wilmut and his team have abandoned their plans to pursue cloning technology in order to obtain patient-specific embryonic stem cell. Instead, they decided to focus all their work into perfecting the nuclear reprogramming (iPS) technique. Much ethical concern that rises by the use of cadaveric fetal tissue was considered by the Polkinghorne Committee in 1989. They concerned on the responsible use of aborted fetal tissue in deriving EG cells. However, does the use of fetal tissue for derivation of EG cells raise additional concern which might require the tissues for further safeguards? Currently, the use and derivation of EG cells does not require special licence from the statutory board but would be regulated by ethics and research committees. They have already approved the use cadaveric fetal tissue in patient suffering from Prakinson’s disease. The ethical acceptability of abortion is closely linked to the use of fetal tissue for the derivation of EG cells. The remarkable potential of EG cells to create useful cell lines for transplantation raises the possibility of misusing this technology through inappropriate incentives that enter into a woman's decision to request an abortion. Women can be exploited to seek for abortion with the view to in return, receive possible financial or therapeutic benefits though donating their cadaveric fetal tissue. A written consent must be obtained from the mother for the use of its fetal tissue, whether or not to allow the tissue to be used for research and therapy. The mother should be given all relevant information and proper counselled about the implications of taking the proposed steps to enable her to make proper judgement when writing the consent.

There are also issue regarding the usage of pre-implantation genetic diagnosis to save a sibling. Through in vitro fertilization, left over of embryos in IVF clinics are simply discarded. Report shows that more than 300 00 of unused embryo are discarded in the US alone. Would it be appropriate to take organs from dying patient before they even died in order to increase someone else chance for cure? Consider the case of Adam and Molly Nash. Six-year-old Molly Nash was diagnosed with a fatal genetic disorder, Fanconi-anemi known to be a progressive disease for which the only proven therapy is a bone marrow transplant. Her parents produced 15 embryos through IVF, by which only one had the right genetic material (cell that matched Molly but without anemia). The other unused embryos were discarded. The desired embryo was implanted to give birth to Adam. Upon his birth in 2000, Adam’s umbilical cord blood was transplanted into Molly and the treatment gave Molly an 85% chance to beat the disease. The controversial fact remains that Adam was conceived, not just to be a son, but a medical treatment. If he didn’t carry the intended genetic material, he would have been rejected. This narrows down to a conclusion that we are growing humans for body parts. We are generally new to this technology and are not aware of the unknown potential effects of stem cells. In March 2001, a tragic side effect from an experiment involving insertion of fetal brain cells into the brains of Parkinson’s disease patient was reported. The result includes uncontrollable movements. The report suggested that patient with severe Parkinson's disease who survived from the transplants of Human embryonic dopamineneuron results in some clinical benefit in younger but not in older patients. Adult stem cells in all fairness do not proliferate as well as ES and have restricted differentiation potential. They can also be used to treat leukemia, brain tumour, breast cancer, lupus and other chronic diseases. However, current clinical applications of adult stem cells are abundant. So for the time being, I suppose that it is better to continue using adult stem cell in medical therapy. ES on the other should undergo intensive research before it is being used as medical therapy. As science and technology continue to develop, so do the ethical viewpoints surrounding this advancement. It is very crucial to educate and explore the issues, scientifically and ethically in order to fully understand how this advancement really work and how human kind can benefit from it without violating any rights.

International society for stem cell research. (2011). Sem Cell Facts. Retrieved from Ariff Bongso, M. R. (2004). History and perspective of stem cell research. Best Practice & Research Clinical Obstetrics and Gynaecology, 827–842. Austriaco, F. N. (2008). Understanding Stem Cell Research Controversy and Promise. USA: Knights of Columbus Supreme Council. Curt R. Freed, P. E. (2001). Transplantation of embryonic dopamine neurons for severe parkinson's disease. The New England Journal of Medicine, 344 (10). Guido de Wert, C. M. (2003). Human embryonic stem cells: research, ethics and policy. Human Reproduction, 672-682. Hollowell, K. (2002). TEN PROBLEMS WITH EMBRYONIC STEM CELL RESEARCH. California: INSTITUTE FOR CREATION RESEARCH. Kolata, G. (2001). In Cloning, Failure Far Exceeds Success. The New York Times. Malaysia Medical Council. (2002/2009). STEM CELL RESEARCH & STEM CELL THERAPY GUIDELINE OF THE MALAYSIAN MEDICAL COUNCIL. Malaysia: Malaysian Medical Council. National Institutes of Health. (n.d.). Stem Cell Information, The official National Institutes of Health resource for stem cell research. Nuffield Council on Bioethics. (2000). Stem Cell Therapy:the ethical issues. Bedford Square, London: Nuffield Council on Bioethics.


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