Stem Cell Research and Therapeutic Cloning- final

Letter of Transmittal

September 26, 2016

Head of Department, Research and Development

Company ABC

(Address)

Attn. Mr/Mrs/Miss. (Name)

Enclosed hereinafter is the report encapsulating the preliminary research you ordered pertaining the type of stem cells apposite for use in developing an innovative evidence-based therapies for purposes of reducing microcephaly growth in the unborn babies ensuing from pregnant women infection with the Zika virus. This document has endeavored to look into the legal as well as ethical arguments related to the use of embryonic stem cells in formulating therapeutic cloning. The report presents the ethical justifications and shortcomings of using embryonic stem cells research in therapeutic cloning as well as accentuating the ethical steps and research design.

Hoping you find this report resourceful.

Sincerely yours,

(Students Name)

Ethical Issues in the Use of Human Stem Cell Research in Therapeutic Cloning

Student’s Name

Institution’s Name

Date

Table of Contents

TOC o “1-3” h z u Abstract PAGEREF _Toc462820546 h 4Introduction PAGEREF _Toc462820547 h 5A Recapitulate of Business Ethics for Pharmaceuticals PAGEREF _Toc462820548 h 6Embryonic Stem Cell Production Through Therapeutic Cloning PAGEREF _Toc462820549 h 7Ethical Arguments for Embryonic Stem Cell Research in Therapeutic Cloning PAGEREF _Toc462820550 h 10Conclusions and Recommendations PAGEREF _Toc462820551 h 11References PAGEREF _Toc462820552 h 14

AbstractStem cells are unspecified cells capable of dividing and producing copies of themselves and are able to differentiate. Due to their ability to produce other cell types in the body, scientists explore their potential use in regenerative medicine. It is particularly pertinent to note that embryonic stem cells come with huge therapeutic potential since they can produce every cell type in the body in comparison to stem cells from adult tissues whose ability is limited to the differentiation of few cell types. This forms the rationale for emphasis on embryonic stem cell research. Nonetheless, this research precipitates sensitive ethical, religious and legal debates which are weighed against potential great benefit of such research for patients suffering from incurable diseases. The ethical restrictions on embryonic stem and therapeutic research are questionable in the view that they inhibit the formulation of techniques that hold potential for successful application of pluripotent stem cells in clinical treatment of severe diseases such as Zika virus. The purpose of this report is to highlight the main ethical and legal arguments in validating and against human embryonic stem cell research. This report argues that the ethical concerns are less problematic through the use of therapeutic cloning as compared to the use of fertilized eggs as the source for stem cells. The moral status of an enucleated egg transplanted with a somatic cell nucleus if deemed to be more clearly not equivalent to that of a human being. Subject to ethical considerations alone, embryonic stem cell research coupled with therapeutic cloning ought to be encouraged in a bid to develop therapeutic applications of human stem cells.

Ethical Issues in the Use of Human Stem Cell Research in Therapeutic Cloning

IntroductionThe idea of ethics in business operations is very pertinent in today’s corporate world and invariably deals with ethical and moral actions of individuals and organizations. Issues arise when organizations have an obligation to comply with multiple legal and cultural requirements some of which tend to be in conflict. This is also true for corporations that expand their businesses in foreign countries where varying practices are relatable. There is a concern whether such corporations ought to abide by the laws of their home countries or should they follow the less stringent laws in the developing countries which they set up business (Noordin n.d.). In determining the corporate achievements of the pharmaceutical company, it is vital to evaluate the philosophical, ethical and political underpinnings in its conduct of doing research. It is crucial for any organization to elude from engaging in any conduct that may precipitate into criminal and civil liability and actions that might adversely affect its corporate image and reputation. Consequently, a company need not only seek to make profits and expand its niche in the market but also ensure it avoids dealing in actions that might result in adverse economical and ethical costs to its staff, consumers, general public and the environment.

The scenario of Company ABC endeavor to develop novel therapies for the Zika virus in pregnant women by illuminates on a wide spectrum of ethical issues in business operations. There are instances when there is a disconnection between corporate’s code of conduct and the actual practices of organization. Although companies may rely on this merely as a marketing tool, the misconduct ought to be unequivocally sanctioned by authorities. Although PharmaCare claims to observe corporate social responsibility, there seems to be a lack of commitment to principled expedition of business that is intended to pursue corporate accountability and corporate governance. Ethical Issues in the Use of Human Stem Cell Research in Therapeutic Cloning

The pharmaceutical industry is customarily involved in the research, development, production, marketing and distribution of drugs and therapies to patients and health professionals. The pharmaceutical industry is the most heavily regulated of all industries. Due to the gravity of the human wellbeing, the industry is clearly the most heavily reliant on a code of ethics in its daily practice. Pharmaceutical companies are responsible for supplying and compounding drugs, formulating proper dosage forms for administration of drugs in areas relating to patient pharmaceutical care, manufacturing, community pharmacy and research. Their operations invariably involve gathering, identification, sanitization, separation, blending, clinical trials, standardization and quality control of medicinal substances. All these areas form the foundation for the requirement of a set of ethics guidance.

A Recapitulate of Business Ethics for PharmaceuticalsThe use of human stem cell in therapeutic cloning presents an ethical quandary as regards to the operations of Company ABC. While the corporation has a legal and moral duty to provide exceptional standard of equitable healthcare that is evidence based, it resort to the use of human stem cell research may raise the issue of Good Manufacturing Practice. Good Manufacturing Practice (GMP) provides a quality system covering the manufacture and testing of pharmaceutical dosage forms or drugs. It outlines the aspects of production and testing that can impact the quality to a product. The basic requirements of GMP include: ensuring that all manufacturing process are clearly defined, systematically review for consistency in the production of a medicinal product of the required quality and specification and ensuring that critical steps of the manufacturing process and significant changes to the process are validated. Company ABC needs not violate the good manufacturing practice through lack of adequate and appropriately qualified and trained personnel, suitable equipment, correct materials, and approved procedures and instructions for manufacturing and suitable storage and transportation.

Embryonic Stem Cell Production Through Therapeutic CloningProduction of embryonic stem cells from unfertilized cells transplanted with a nucleus from a patient cell may result in immunological compatible replacement tissues in inherited or severe degenerative diseases (Koch et al. 2013). Currently, research as well as development of that involves human embryonic stem cells is prohibited in many parts of the world, while in some only the use of embryonic stems cells created from the blastocyst stage of fertilized eggs in surplus from fertility treatment is permitted (Schuklenk & Ashcroft 2014). With stem cell based treatment being potentially beneficial to patients with severe diseases and with therapeutic cloning offering a way to generate clinically superior stem cells, the current resistance to permitting this technique to be developed through research may be deemed in itself unethical at the onset (Hyun 2010).

Nonetheless, the objection is subject to two preponderant issues. Firstly, the harvesting of stem cells involves the destruction of the pre-embryo at the blastocyst stage (6 days), and in the event the pre-embryo at this stage is recognized as a human being with inalienable right to life, it would prohibit stem cell harvesting whether the blastocyst were consequent of therapeutic cloning or as a result of a surplus unfertilized egg (Kiatpongsan & Sipp 2009). Secondly, the therapeutic cloning employs the same technique as the one used in the initial stage of reproductive cloning, in which an enucleated egg is transplanted with a somatic cell nucleus and implanted in a susceptible uterus in a bid to produce an infant. The development of therapeutic cloning may hence be dreaded to create a way for an otherwise unacceptable use, and this risk may be considered sufficiently great to prohibit therapeutic cloning save for the potential benefits to patients (Larijani & Zahedi 2008).

It can be considered that the prospective of an in vitro blastocyst to advance into a fetus subsequent to a sequences of reliant techniques, comprising of successful implantation, converses an exceptional ethical standing regardless of whether the blastocyst is a consequence of in vitro fertilization or an effect of nuclear transference from a somatic cell to an unfertilized, enucleated egg cell (Larijani & Zahedi, 2008). The “potentiality” debate has been used to contend in favor of the complete human ethical status of the fertilized egg from fertilization headlong. This implies that what might certainly, devoid of auxiliary external interference, develop into human being should be taken as a human being naturally (Schuklenk & Ashcroft 2014).

In the strictest sense of the term, “potential” translates to the fact that an entity can achieve or become something that in the current moment isn’t. This entails one, identifying that it continues to be what it is in some key aspect, and two that the potential is intrinsic, implying that it doesn’t need something indispensable from the external (Gupta 2011). Subsequently, the in vitro blastocyst having latency for personhood does not meet either of these two conditions. Obviously the blastocyst cannot be a newborn human, it possibly will become one, and while this progression could take place in the conventional course of events, it may also develop into two or more children or it might not develop at all, whether by means of failure or by way of a choice not to implant the fertilized or transnuclear egg (Sui 2013). It can therefore be inferred that it might be considered that neither is identity inevitably conserved nor is the development self-determining without external conditions and liable choices by other players (Lo & Parham, 2009).

While the in vitro blastocyst might form a crucial foundation for the consequent development of a human being it is not one in itself. Subsequently, the human ethical status cannot be concluded from a prospective which it does not intrinsically have at the onset (Koch et al. 2013). Nonetheless, subject to the essential role the fertilized egg or blastocyst has in the development of the genetic milieu from which a human being could arise it might be decided to deliberate some distinctive respect or ethical standing on it or even respect it as if it were a human person (Hyun 2010). Whether such ethical hypothesis is well founded falls outside the focus of this report.

Embryonic stem cell research in the light of therapeutic cloning offers an enormous potential for clinical applications including the use of embryonic stem cells product as a route to gene delivery and cell replacement therapy in regenerative medicine (Lo & Parham 2009). Moreover, embryonic stem cell research might, in the near future, sanction in vitro organogenesis and neutralize senescence. The blend of therapeutic cloning and gene therapy provides a huge prospective for patient-specific salvage of a genetic mutation of the loss-of-function kind, ensuing to eliminated or lowered activity of a specific protein (Koch et al. 2013). Embryonic stem cells coupled with therapeutic cloning used in cell replacement therapy offers the opportunity to develop innumerable types of tissues, some of which include osteoblasts aimed at offsetting osteoporosis, and spinal cord regeneration ensuing trauma (Schuklenk & Ashcroft 2014). The subsequent regaining of motility could result into clinical applications for paralysis in humans by way of therapeutic cloning. Fascinatingly, embryonic stem cell research together with therapeutic cloning can offer a solution to low human oocyte obtainability and an encouraging therapeutic approach to avoid infertility. As reported by Lo & Parham (2009) artificial gametes can be developed by haploidization, by use of embryonic stem cell differentiation in an enucleated oocyte set to undertake meiosis once induced. Tesarik et al assimilated the nucleus of a human cumulus cell into an enucleated allogenic oocyte (Gupta 2011). They obtained a 50 percent success rate in haploidization, with two out of the six artificial oocytes being efficaciously fertilized in vitro and defrosted for probable implantation (Hyun 2010).

It is imperative to accentuate that the reprogramming of somatic cells for purposes of producing induced pluripotent stem cells (iPS cells) circumvents the ethical difficulties that are explicit to embryonic stem cells (Larijani & Zahedi 2008). Even so, there are problematic ethical quandaries with any human stem cell (hSC) together with the consent to bequeath materials for hSC research, initial clinical trials for hSC therapies, as well as regulation of hSC research (The Irish Council for Bioethics 2008).

Ethical Arguments for Embryonic Stem Cell Research in Therapeutic CloningEthical Issues Therapeutic cloning and stem cell research yields an ethical controversy subject to the origin of embryonic stem cells. The sources of the embryonic stem cells include those taken from aborted fetuses, embryos morphologically incapable of in utero implantation, and unutilized zygotes, with embryos morphologically incapable of in utero implantation accounting for 60 percent of all embryos developed through IVF (Hyun 2010). Some commentators have considered using of discarded embryos minuscule due to the fact that they imply reutilizing life products.

The illusion of the primeval stripe guiding differentiated development converses to the two-week embryo an advanced moral and ethical standing as a prospective human person, in comparison to the initial embryo at the phase of a randomly-organized assemblage of cells. Accordingly, laws barring the culture of embryos for more than two-weeks, with two weeks marking the inception of gastrulation as well as the formation of the embryonic line, are in potency in numerous countries including the United States, subject to a ruling of the British Warnock Commission in 1984 (Sui 2013).

The ethical argument on the moral impermissibility of considered obliteration of an embryo can be avoided by a new technique developed by Chung et al (Kiatpongsan & Sipp 2009). They productively developed human embryonic stem cell from a single cell devoid of rescinding the blastocyst in the process. The employed the same operations routinely devoted to genetic screening in pre-implantation embryos. This technique seems to be capable of resolving the ethical apprehension of destroying a human embryo, therefore making it practicable the prenatal creation of individual-specific cell lines for purposes of regenerative medicine (Lo & Parham 2009). Conversely, this method fails to transform the outcome of the ex vivo embryo, due to the latter having a lean chance of implantation.

Conclusions and RecommendationsWhile a number of scientific hindrances remain baffling, the medical advantages that could arise from treatments subject to therapeutic cloning prevail over the ethical impasse and hence calling for auxiliary enhancements to be clinically pertinent (Kiatpongsan & Sipp 2009). Generally, therapeutic cloning exhibits great potential as a histo-compatible technique for cell replacement therapy in a bid to reinstate motility ensuing from paralysis, lessen senescence, as well as repair damages done by stroke, myocardial infarction, liver cirrhosis, severe burns and microcephaly from Zika virus infection. Utilized as a substitute to viral vectors, patient-specific cell lines developed through embryonic stem cell research can be employed together with gene therapy for purposes of treating conditions brought about by genetic defects. Transgene supplement could be instrumental prior to in vivo transplantation of the ntESC in a bid to improve graft endurance, differentiation and integration (Sui 2013). The other uses of therapeutic cloning include, though not limited to, the diagnosis of epigenetically initiated cancer as well as the fashioning of a treatment using embryonic stem cell. The major scientific problems include tumorigenicity, interspecies transfer of pathogens, in vitro unstructured differentiation, epigenetic reprogramming of the genome, low oocyte obtainability, mitochondrial heteroplasmy and the likelihood of graft rejection (Sui 2013). Ethical argument on the source as well as destruction of embryos and the contradictory legislations blended with scarcity of funding work as an impediment to the improvements in therapeutic cloning. Future reflections would be aimed at unifying all necessary laws, and establishing a clear discrepancy between therapeutic and reproductive cloning in the redaction of laws pertaining to the therapeutic cloning development of embryos. Incidentally, a clear comprehension of the research and ethical issues relating to therapeutic cloning is obligatory in ensuring the improvement in the clinical applicability devoid of falling into unfettered abuses (Kiatpongsan & Sipp 2009).

Research studies have indicated that six days following in vitro fertilization or nuclear transplantation, the blastocyst yields an orb of cells. Resultant from this biological matter in vitro, pluripotent stem cells and other biological products of value for the treatment of medical illnesses can be developed devoid of a compromise to the essential human right to life (Larijani & Zahedi, 2008). However, such a procedure entails the obliteration of the blastocyst and consequently the irretrievable abolition of the probability for fetal growth after placement into a uterus (Schuklenk & Ashcroft 2014). Development of embryonic stem cells from trans-nuclear unfertilized egg cells can be considered to have even fewer ethical difficulties opposed to harvesting of stem cells from fertilized eggs in excess from fertility procedure (Sui 2013). This fact together with the significant therapeutic latency provided by the creation of immunologically attuned, as well as genetically modified, tissue from such trans-nuclear stem cells, ought to make somatic nuclear transformation into unfertilized egg cells a favorite procedure that permits promotes incentives and focused research exertion, as opposed to legal restrictions (Lo & Parham, 2009).

ReferencesGupta, B.D. (2011): An Introduction to Stem Cell and Debate Surrounding Them. J Indian Acad Forensic Med, 31(3):267-273.

Hug, K. (2005), Sources of Human Embryos for Stem Cell Research: Ethical Problems and their Possible Solutions, Medicina (Kaunas) 2005: 41 (12).

Hyun, I. (2010). Allowing Innovative Stem Cell‐Based Therapies Outside of Clinical Trials: Ethical and Policy Challenges. The journal of law, medicine & ethics, 38(2), 277-285.

International Society for Stem Cell Research (2009), Guidelines for the Conduct of Human Embryonic Stem Cell Research, Version 1, December, 2016, Retrieved from < https://www.forth.gr/_gfx/pdf/ISSCRhESCguidelines2006.pdf>

Kiatpongsan, S., & Sipp, D. (2009). Monitoring and regulating offshore stem cell clinics. Science, 323(5921), 1564-1565.

Koch, V. G; Roxland, B. E; Pohl, Barbara, P. & Keech, S. K. (2013), Contemporary Ethical Issues in Stem Cell Research, S. Sell (ed.), Stem Cells Handbook, DOI 10.1007/978-1-4614-7696-2_2,

Larijani, B., Zahedi, F. (2008): Policy, Equity and Priority: Ethical Issues of Stem Cell in Developing Countries. Iranian J Publ Health, 37(1):1-11.

Lisker, R (2003), Ethical and Legal Issues in Therapeutic Cloning and the Study of Stem Cells, Review Article, Archives of Medical Research 34 (2003) 607-611

Lo, B. and Parham, L. (2009), Ethical Issues in Stem Cell Research, Endocrine Reviews, 2009 May: 30 (3): 204-213

Mollar, M.S. (2008): Human Embryonic Stem Cell Research, Justice, and the Problem of Unequal Biological Access. Philosophy, Ethics, and Humanities in Medicine, 3(22):1-13.

Pandey, A (2016), Stem Cell Research in India: Socio-Ethical Concerns, Research Article, International Journal of Advanced Research, 2016, Vol. 4, Issue 1, 282-289, ISSN 2320-5407

Noordin M.I. (n.d.). Ethics in Pharmaceutical Issues. Department of Pharmacy, Faculty of Medicine, University of Malaya, Malaysia. Retrieved from <http://cdn.intechopen.com/pdfs/31746/InTech-Ethics_in_pharmaceutical_issues.pdf>

Schuklenk, U. & Ashcroft, R. (2014), The Ethics of Reproductive and Therapeutic Cloning (Research), Monash Bioethics Review, April 2000, Vol. 19, Issue 2, pp 33-44. Online ISSN 1836-6716

Sui, S (2013), Stem Cell and Ethics, Centre for Bionetworking, Retrieved from http://www.centreforbionetworking.org/wp-content/uploads/2013/12/Stem-Cell-Research-and-Ethics-.pdf