Embryonic Stem Cell Research Paper

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The advent of stem cells into the public arena in 1998 raised hopes for the treatment of a host of debilitating diseases affecting many organs and tissues of the body. The stem cells on which most attention was paid were embryonic stem cells, on account of their enormous biological potential. However, their derivation from human embryos raised major ethical qualms, involving as it does the destruction of embryos. The hype accompanying stem cells has had repercussions ranging from medical tourism to scientific fraud. The emergence in 2006 of induced pluripotent stem cells added to the clamor surrounding stem cells, since these appeared to surmount the ethical problems through bypassing an origin in embryos. These stem cells are obtained by reprogramming adult body cells so that they revert to a pluripotent state and appear to have a potential akin to that of embryonic stem cells. Embryos from which embryonic stem cells are derived may be nonviable, surplus embryos from IVF programs, embryos produced for research purposes, embryos created using somatic cell nuclear transfer, and human admixed embryos. Policy and regulatory frameworks governing the production of embryonic stem cells fall into four dominant categories, each with differing underlying ethical strictures and also with substantial scientific and clinical repercussions. The comparative status of embryonic and induced pluripotent stem cells is assessed both scientifically and ethically.


It was in 1998 that human embryonic stem cells (ESCs) gained prominence when they were first successfully derived from human blastocysts, that is, early embryos (Thomson et al. 1998). Besides reproducing themselves sustainably and indefinitely in culture (self-renewal), these cells also maintain the developmental potential to form derivatives of all three embryonic germ cell layers. Such pluripotency enables them, under appropriate conditions, to become all the tissues in the body. These include gut epithelium (from endoderm); cartilage, bone, and muscle (from mesoderm); and neural epithelium and stratified squamous epithelium (from ectoderm). It is this latter property that is the distinguishing mark of embryonic (as opposed to adult) stem cells (Towns and Jones 2004). The potential of this discovery lay in its ability to produce large, purified populations of cells and neurons, particularly in diseases resulting from the death or dysfunction of one or a few cell types, such as Parkinson’s disease and juvenile-onset diabetes mellitus. These prospects were accompanied by two sets of problems: ethical and the unrealistic expectations surrounding them.

The ethical problems arise because deriving stem cells from embryos entails their destruction, an act that immediately raises the contentious question of the moral status of embryos. For many, the use of ESCs is repugnant, as opposed to the use of adult stem cells (ASCs) that are regarded as ethically neutral. This, in turn, raises the question of the relative therapeutic efficacy of the two types. This is a scientific and clinical issue, although some who regard the use of ASCs as ethically preferable tend to conflate ethical and scientific arguments. This leads to highly contested claims that ASCs are therapeutically superior to ESCs. The result is a confusing mix of scientific, ethical, and theological considerations.

The debate on ESCs has been made far more problematic by the unrealistic expectations of the public, based on hype and exaggerations of the therapeutic potential of stem cells (ASCs as well as ESCs). This has led to a massive growth in stem cell tourism, as patients and their families search for the wonder cures promised by various clinics from the injection of stem cells. Unfortunately, most of these are not backed up by stringent peer-reviewed publications. This mixture of false hope and hype has tarnished the reputation of stem cell research, made worse by the excessive hype of legitimate researchers who sometimes make unrealistic claims about the short-term therapeutic benefits of stem cell advances in the clinic.

Public Face Of ESCs

These and other intense pressures on stem cell researchers have had an even more tragic outcome, namely, the blossoming of pernicious scientific fraud in the stem cell arena. The major contributor to this dubious hall of fame was Hwang Woo-Suk who in 2004 appeared to have become the first scientist to clone human embryos and extract stem cells from them. This was followed in 2005 with the claim that his team had created the world’s first ESCs using genetic material from patients and therefore matched to these patients. Later that year, he went further with the birth of the world’s first cloned dog. The hype surrounding these breakthroughs was intense, but everything began to unravel when a series of ethical and scientific irregularities emerged, leading to serious questioning of the validity of the isolation of human ESCs (Cyranoski 2004, 2014). It was only far more recently, in 2013, that the production of patientspecific ESCs through cloning has been unequivocally accomplished (Tachibana et al. 2013). Misconduct has also marred ASC research.

Cardiologist Bodo-Eckehard Strauer claimed to have saved the life of a patient suffering from cardiogenic shock by transplanting adult autologous bone marrow-derived stem cells into a damaged artery. Described as a global innovation, the results based on a small number of cases have been severely critiqued on a range of fundamental errors, discrepancies, and contradictions (Francis et al. 2013).

Another striking debut for ESCs has been into the world of politics. In the United States, President George W. Bush spoke to the nation on 9 August 2001 about ESC research, when he declared that “embryonic stem cell research is at the leading edge of a series of moral hazards.” (Bush 2006) At that time, he announced that the use of NIH (federal) funds would be permitted for research on an estimated 60 stem cell lines already in existence as of that date. These lines must have been derived from embryos surplus to the requirements of IVF programs. No new embryos could be destroyed in deriving ESCs using federal funds. The aim of this dictate was to encourage respect for human life at the same time as exploring the promise and potential of stem cell research in finding cures for debilitating diseases. It is unfortunate that the stem cell lines already in existence, plus additional ones potentially eligible for federal research funding, failed to live up to ethical standards set by the Food and Drug Administration (FDA) (Jonlin 2014).

Emergence Of iPSCs

A major breakthrough came in 2006 with the first description of induced pluripotent stem cells (iPSCs). This landmark study demonstrated that skin cells can be reprogrammed into stem cells. This was the first direct reprogramming of differentiated mammalian somatic cells back to a pluripotent state by transfecting the cells with four transcription factors (Takahashi and Yamanaka 2006). The resulting iPSCs appear very similar to ESCs and are also patient specific. Possible uses for iPSCs in human therapy include in vitro disease modeling (so-called disease in a dish), high-throughput drug discovery and screening, regenerative therapies, and even novel reproductive techniques.

The immediate response to these developments was positive, since they gave the impression of opening doors that had been shut on account of the ethical quandaries associated with ESCs and the destruction of embryos. Unfortunately, dubious and even fraudulent scientific studies were not far behind this Nobel Prize-winning work. A very short-lived episode hit the headlines in 2012 when Hisashi Moriguchi claimed to have cured six heart failure patients with cells derived from iPSCs. It soon emerged that these claims were baseless. In 2014, a major simplification of the iPSC technique developed by Haruko Obokata created international interest with the description of STAP (stimulus-triggered acquisition of pluripotency) cells. Together with coworkers, she had described how cells of various types, including skin, muscle, and lung cells, could be rapidly changed into an embryonic-like state by being dipped in a mild acid solution. However, issues quickly emerged over irregularities in images, suggesting at the least innocent mistakes and at the worst fraud.

Embryos And ESCs

ESCs are derived from the inner cell mass (ICM) of early embryos at the blastocyst stage, 5–7 days after fertilization. These ESCs have the ability to create all the cell lines of the embryo/fetus but not the individual itself. At present, their extraction disrupts the ICM and therefore destroys the blastocyst. The embryos used in this way have a number of sources (Jones and Whitaker 2009).

The first of these is nonviable embryos created via IVF. These will not be transferred to a woman since they are biologically incapable of further development. Use of these embryos is not contentious.

Second, and far more important in practice, is surplus embryos created during IVF programs. While created for implantation into a woman, they are no longer required for reproductive purposes. These embryos are viable, but unless donated to others in an IVF program will eventually be destroyed (allowed to thaw) since most legislation prohibits the indefinite frozen storage of surplus embryos. Since these embryos were created for reproductive purposes, it is possible to procedurally separate the decision to destroy surplus embryos from the decision to use them for research. This decreases the likelihood of exploitation and coercion.

The third source is embryos created specifically for research purposes. In this case, the destruction of embryos is premeditated, with research as the only end point. There is no intention that the embryos will be allowed to develop into human beings. For many, this is a threat to human dignity, since it represents a further step in the instrumentalization and commodification of human life. However, societies that approve of procedures, such as IVF, prenatal diagnosis, preimplantation genetic diagnosis (PGD), and the creation, storage, and destruction of surplus embryos, give only limited respect to early embryos. Any differences between these procedures and those producing embryos explicitly for research purposes are ones of intention. However, in the research paradigm, embryos are being produced as a means to an end, and this sets this source apart from any others.

A fourth source takes the research goal further with the creation of embryos using somatic cell nuclear transfer (SCNT). The difference between this source and the creation of research embryos using IVF lies in the way in which the embryos are created. An argument against allowing SCNT (research cloning) is that it is the beginning of a “slippery slope” toward reproductive cloning and a devaluation of human life in general. A different concern is that SCNT could result in an improper use of women’s bodies by creating a market for human eggs. This in turn may lead to the exploitation of poorer women, who would be the most likely to sell their eggs.

In an effort to combat the shortage of human eggs, a fifth source is that provided by human admixed (interspecies) embryos created for research purposes. This uses animal eggs to create a “cytoplasmic hybrid.” The differences between embryos created via IVF or SCNT on one hand and the admixing of species on the other appear to be minor, although another biological boundary has been breached.

While this discussion has centered on the use of embryos for research, it is pivotal for the ESC debate, since ESCs can only be obtained from these embryos. Additionally, the embryos are in vitro blastocysts (those in the laboratory) and not in utero blastocysts (those in a woman’s uterus and in an environment congenial to further development). While the latter have the potential of producing human individuals (totipotent), in vitro blastocysts have no such potential in the laboratory. Those on which research is conducted never acquire this potential, since research on human embryos beyond 14 days is currently forbidden.

Policy And Regulatory Frameworks Governing ESCs

Regulations governing ESCs fall into four dominant positions. These were designated A to D by Towns and Jones (2006). Position A encompasses countries that prohibit all embryo research and therefore the extraction of ESCs. Position B confines the use of embryonic stem cells to those currently in existence, in that they were extracted prior to a specified date, thereby prohibiting the extraction of ESCs and utilization of ESCs derived in the future. Position C allows for the use and ongoing isolation of ESCs from surplus IVF embryos from IVF programs. Position D allows the creation of human embryos specifically for research via both fertilization and SCNT. The Hinxton Group (An International Consortium on Stem Cells, Ethics and Law 2006) again identified four groups: Prohibitive (equivalent to A), Restrictive Compromise (B), Permissive Compromise (C), and Permissive (D). The classification adopted by the European Science Foundation (2013) is similar but omits a position B equivalent. The groups are Very Restrictive (corresponding to A), Permissive (C), and Very Permissive (D), with further categories of Restrictions by Default (where legislation is not explicit but national practices are quite restrictive in practice) and Unlegislated (where there is no legislation on human ESCs).

While some countries have moved between categories over recent years, the current situation is exemplified by the following examples:

  1. (Prohibition): Italy, Slovakia, Tunisia
  2. (Restrictive Compromise): United States – use of federal funds under President Bush
  3. (Permissive [Compromise]): Iran, Saudi Arabia, China (Hong Kong), Taiwan, Canada, Denmark, France, Cyprus, Greece, Hungary, Iceland, the Netherlands, Norway, Portugal, Spain, Switzerland, Australia, United States – use of federal funds under President Obama
  4. ([Very] Permissive): United Kingdom, Singapore, Japan, Israel, Belgium, Sweden, South Korea, certain states in the United States using private funds

Restrictive by Default: Romania, Turkey, New Zealand

Unlegislated: Austria, Ireland, Luxembourg, Poland

Position A (Prohibition) exemplifies the stance that human life commences at fertilization, allowing nothing to be done to the embryo that is not in its best interests. Such a stance would also be expected to disapprove of IVF, the production of surplus embryos, and the derivation of ESCs from these embryos. Its emphasis is entirely on harm done to embryos, rather than on benefits that might accrue from research using ESCs. It neglects any interests beyond those of the very early embryo, including those with fertility problems.

The intention of position B (Restrictive Compromise) was to allow some research on human embryos, while aiming to protect embryos. This was achieved by allowing research only on stem cell lines already in existence, since the embryos from which these lines had been extracted had previously been destroyed. The destruction of any further embryos was forbidden. This compromise position took note of the plight of people with severe degenerating conditions who could, possibly, benefit from scientific advances (Towns and Jones 2006). However, these restrictive ESC guidelines fail to protect the large numbers of embryos destroyed daily by IVF procedures in fertility clinics.

Position C (Permissive [Compromise]) limits ESC research to surplus embryos from IVF programs. This allows both the utilization and extraction of new ESCs and eliminates arbitrary time limits on extraction. It accepts the destruction of already existing embryos no longer required within IVF programs. These in vitro blastocysts have no future as human individuals, since the decision has already been taken that they will not be donated to other individuals within an IVF program. This position therefore seeks to improve the health status of individuals suffering from common debilitating conditions, alongside providing early embryos with the care and respect due to human tissue.

Position D ([Very] Permissive) represents a dramatic moral shift since embryos are being created solely for research purposes, their creation being for the benefit of scientific research into developmental phenomena. As research subjects, the embryos do not benefit, neither are their interests taken into account. While the scientific exploration will probably have a therapeutic rationale, any claims made for this work are to be realistic. Justification is also needed why this research cannot be conducted on surplus embryos.

Human Admixed Embryos

Hybrid embryos (true hybrids) are those created by the fusion of gametes from human and nonhuman animals to produce an embryo which is a genetic mix of the contributing species. Cytoplasmic hybrids (cybrids) are created by performing SCNT to introduce a somatic cell from one species (e.g., human) into an enucleated egg from another. Cybrids allow the creation of stem cells from adult somatic cells without the use of human eggs. This enables stem cell lines to be derived from individuals with diseases that may subsequently be studied in the resulting stem cells. Chimeric embryos are created by inserting stem cells from one species into an existing embryo of another (e.g., mouse cells to human embryos). The aim is to produce particular types of stem cell lines or to examine how stem cells develop in the embryo.

The UK debate on the Human Fertilization and Embryology Bill brought the opposing arguments into the open (HFEA 2007). Scientists in favor of allowing the production of human admixed embryos argued that it will assist in the study of normal embryonic development and genetic disease, including a range of conditions such as motor neuron disease, Alzheimer’s disease, Parkinson’s disease, and some cancers. For supporters of the bill, such work is an inherently moral endeavor, since its aim is to harness the potential of stem cell research for the benefit of human health. The arguments of opponents vary but include the unnaturalness of the procedures and the crossing of species boundaries. For some, they are morally repugnant and violate human dignity. While they may promote a mechanical view of the world, they are not devoid of moral boundaries. Moral repugnance is an unpredictable basis for moral judgments, although sentiments of disgust are deeply ingrained warning signs that alert us to moral wrongs. Species integrity may allow us to preserve a coherent, familiar moral terrain, although this has to be balanced against the prospective benefits held out by research of this nature.

Will iPSCs Replace ESCs?

The advent of iPSCs in 2006 was seen by many as a major breakthrough, not only on the scientific front but also for the ethical debate over the destruction of embryos to obtain ESCs. Initial responses by some commentators deemed them ethically unproblematic, the underlying premise being that iPSCs are scientifically very similar, or even identical, to ESCs. In spite of such assurances, especially by those opposed to the use of ESCs, there remain a series of practical and ethical considerations. Since this is a rapidly changing field, views will probably continue to undergo adjustment for some time to come, although some pointers are available (Bridge 2013).

Many scientific questions remain about both human iPSCs and ESCs, with considerable scientific disagreement regarding the safety and efficacy of the two cell types in future cell therapies. Consequently, most stem cell scientists do not consider that ESCs can be completely replaced by iPSCs. According to this view, ESCs remain the gold standard of pluripotency, and the goal of iPSC research is to achieve an ESC-like state. There is growing evidence that ESCs and iPSCs are not the same at an epigenetic and genetic level. Not only this, ESCs are currently considered to have greater therapeutic potential and to be much closer to being translated into a clinical setting than iPSCs. Consequently, further methodological and functional studies are needed to improve the reprogramming technique to generate iPSCs with therapeutic potential more akin to ESCs. This means that ESCs are still needed to understand the basic mechanism of pluripotency and self-renewal (see Bridge 2013 for details).

A wide array of ESC lines is needed for three reasons. First, the current ESC lines have significantly restricted ethnic diversity. Second, it is important that ESC lines are able to differentiate into the tissues of interest. If they are to be used in regenerative medicine, it is necessary for them to follow a desired lineage of differentiation. Third, in order to study human disease, ESCs need to be created that are disease specific. To date, ESCs representing a relatively small number of heritable diseases have been created, a repertoire that needs to be increased significantly. Successful modeling and development of treatments for genetic disorders would require the derivation of more ESC lines representative of specific human genetic diseases. Hence, instead of circumventing the moral problems associated with ESC research, it is becoming increasingly clear that far more work is required using ESCs as an important comparator for future iPSC research.

An unexpected future ethical dilemma associated with iPSC research would emerge if it becomes feasible to utilize human iPSCs to produce sperm and eggs. Were this to eventuate, these could theoretically be used to create embryos. While this lies in the future, the potential to produce iPSC-derived embryos would raise familiar questions about the moral status of these embryos.

Even if this possibility never sees the light of day, it demonstrates that the emergence of iPSCs has not put an end to ethical deliberation.

As one looks to the future, there are at least three possible scenarios regarding the respective roles of ESCs and iPSCs (Solbakk 2008). The first is that iPSCs might completely replace ESCs. The second is that iPSCs will significantly reduce the number of ESCs needed by replacing them in certain types of research. The final scenario is that ESCs will remain central to the field of stem cell research. There has been a move away from ESC research, but this may reflect political and financial pressures, as much as scientific ones.

Patient safety, effectiveness for use in treatments, accessibility to large numbers of patients, and the moral status of ESCs and iPSCs will continue to dominate scientific and ethical discussion.


The prospects opened up by stem cells are enormous both scientifically and medically. Nevertheless, the ethical challenges are set to remain for the foreseeable future, since these will only disappear if the use of ESCs is replaced by ASCs or iPSCs. This looks unlikely, unless another major breakthrough occurs. Currently, there is no evidence that complete replacement of ESCs (and embryo destruction) will prove scientifically acceptable. This is not the last word ethically, although it strongly suggests that the debate over ESCs will continue unabated.

Bibliography :

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  3. Cyranoski, D. (2004). Korea’s stem-cell stars dogged by suspicion of ethical breach. Nature, 429, 3.
  4. Cyranoski, D. (2014). Cloning comeback. Nature, 505, 468–471.
  5. European Science Foundation. (2013). Human stem cell research and regenerative medicine: Focus on European policy and scientific contributions. Strasbourg: European Science Foundation.
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  10. Jonlin, E. C. (2014). Differing standards fir the NIH stem cell registry and FDA approval render most federally funded hESC lines unsuitable for clinical use. Cell Stem Cell, 14, 139–140.
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  12. Tachibana, M., et al. (2013). Human embryonic stem cells derived by somatic cell nuclear transfer. Cell, 153, 1228–1238.
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  14. Thomson, J. A., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.
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  16. Towns, C., & Jones, D. G. (2006). Stem cells: Policy and ethics. In M. Ruse & C. A. Pynes (Eds.), The stem cell controversy: Debating the issues (2nd ed., pp. 329–341). Amherst: New York, Prometheus Books.
  17. Cohen, C. B. (2007). Renewing the stuff of life: Stem cells, ethics and public policy. New York: Oxford University Press.
  18. President’s Council on Bioethics. (2007). Advancing stem cell science without destroying human life, Domestic Policy Council, The White House.
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