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Science, politics, and religion : the ethical dilemma of embryonic stem cell research

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Science, politics, and religion : the ethical dilemma of embryonic stem cell research
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O'Quinn, Kayla
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Science, Politics, and Religion: The Ethical Dilemma of Embryonic Stem Cell Research
by Kayla OQuinn
An undergraduate thesis submitted in partial completion of the Metropolitan State University of Denver Honors Program
May 5, 2017
Dr. Vida Melvin
Dr. Sheila Rucki Dr. Megan Hughes-Zarzo
Honors Program Director
Primary Advisor
Second Reader


ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH
Science, Politics, and Religion: The Ethical Dilemma of Embryonic Stem Cell Research
Kayla OQuinn
Metropolitan State University of Denver
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INTRODUCTION
The purpose of this study is to further investigate all the types of human stem cells potentially available for research purposes: adult stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). In addition to research, this study will highlight the advantages and disadvantages of using each type of stem cell. For example, a disadvantage of using ESCs elicits great risk because it requires an allogenic transplant. This can lead to the death of a patient from graft-vs-host disease, where the immune system is constantly compromised. However, the use of stem cells goes deeper than just the scientific surface; stem cells cross over multiple disciplines.
The politics, ethics, and religious influences also play a part in the progress of stem cell research. First, politics elicit discontinuity of stem cell research because of leadership change. Therefore, some states take action to determine whether stem cell research can occur, and their actions may encourage stem cell research to become state mandated. Second, ethics causes controversy for ESC research because it requires destruction of an embryo. To combat the controversy, organizations have been established in the governmental and private arenas that promote ethical research. However, it may not be enough. Ethics may lead to restricted research with adult stem cells and iPSCs. Finally, religion influences may shape our societys views on the type of stem cells used in research as seen in Bushs executive order.
Most often politics, ethics, and religion conflict with research involving ESCs. The constant battle that ensues working with ESCs may never be resolved. However, even with all these disciplines influencing ESC research, medical progress can still be achieved through the use of adult stem cells and iPSCs.
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PREIMPLANTATION DEVELOPMENT
Fertilization is when the sperm penetrates the egg producing the zygote that contains genetic material from both parents. Within 24 hours of fertilization the zygote begins to divide. All the cells of the embryo are derived from the zygote and must undergo cellular division as it
Figure 1: Displays the different potencies of stem cells as well as the organs into which
pluripotent stem cells can differentiate (Kumar, et al., 2010).
develops to produce numerous cells. These cells become many different types of cells through differentiation. When cells differentiate, they are becoming more specialized cell types and display more specific functions (Figure 1, Kumar, et al., 2010). For example, a cardiomyocyte is a heart cell that allows the heart to contract.
At the 4-cell stage the embryo becomes spherically shaped and is called a morula (Figure 2, square d4) (Niakan, et al., 2012). The cells of the morula are totipotent, meaning they are able
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to differentiate into all cells of the embryo (Khanlarkhani, et al., 2016); this includes all embryonic structures as well as extraembryonic structures like the placenta and amniotic sac. At the 16-cell stage the morula forms a central cavity (Figure 2, square d4) and the embryo is then called a blastocyst (Figure 2, square d5). The blastocyst consists of two cell populations: the outer cells are the trophectoderm and the inner cells are the inner cell mass (ICM). The cells of the ICM are considered pluripotent and can differentiate into all cell types of the embryo (Hanna, et al., 2010), while the trophectoderm is able to differentiate into extraembryonic structures (Yu & Thomson, 2008). The cells of the ICM are the source of embryonic stem cells for use in research and therapy because they are able to differentiate into various types of organs (Kumar, et al., 2010).
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Figure 2: Following fertilization, the embryo undergoes cell divisions; d0-d3 displays the cell divisions. At d4, the cells compact and form the morula; the zona pellucida is around the morula to serve as a barrier around the embryo. At d5, the blastocyst as formed. The white arrow to pointing to the inner cell mass. By d6, the blastocyst emerges from the zona pellucida, and by d7 the embryo is ready to implant on the uterus (Niakan, et al., 2012).
STEM CELLS
A stem cell is able to self-renew and has the ability to produce differentiated cell types (Jaenisch & Young, 2008). During cellular division, stem cells produce two daughter cells where one daughter cell remains as a stem cell for self-renewal; the other daughter cell will differentiate
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(Martello & Smith, 2014). Because of their ability to self-new and differentiate, research involving adult stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) is significant in advancing the medical field. These cells provide repair for damaged tissue, and regenerate new cells affected by disease.
Stem cells are categorized by developmental potential and their source. Most adult stem cells are multipotent and have the capability to differentiate into several different cells types depending on the tissue of origin. ESCs and iPSCs have the most developmental potential, because they have the capability to differentiate into any cell type of the embryo.
Adult stem cells are already highly utilized in the medical field because they have been used the longest in therapy, and were first used for a bone marrow transplant in the 1950s (Jansen, 2005).
Locations of Somatic Stem Cells
Figure 3: Displays the sources of somatic stem cells also known as adult stem cells. These cells reside in their specific niche (learn.genetics.utah.edu).
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Adult stem cells (Figure 3) reside in differentiated tissue, but are undifferentiated cells. These cells are used to maintain and repair the tissue in which they reside. Adult stem cells can be derived from various sources, including dental pulp, which is in the center of a tooth and contains odontoblasts (Laino, et al., 2006), bone marrow, adipose tissue or fat cells, skeletal muscles, epithelial tissue or skin cells of various organs like the lung, retina, ovaries, and testis (Mimeault & Batra, 2008). The disadvantage of using adult stem cells is the limited potency for which they display. This restricts the areas where they can be transplanted, and they can only be used as treatment for cells that they can produce. For example, hematopoetic stem cells can only produce blood cells, and are unable to produce neurons or cardiomyocytes. A specific type of adult stem cell, the hematopoietic stem cells, can be used as treatment for blood diseases like leukemia (Hosseini, et al., 2016). Brenden Whittaker had a genetic disease that caused a malfunctioning immune system, and Evangelina Padilla-Vaccaro was diagnosed with severe
Photograph: Brenden Whittaker and Evangelina Padilla-Vaccaro (California Institute for Regenerative Medicine (CIRM), 2016) combined immunodeficiency that resulted in a non-functioning immune system. Both received
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treatment that removed their own blood stem cells. The blood stem cells were genetically modified, and re-infused into their bodies, resulting in new blood and fully functional immune systems (CIRM, 2016).
Embryonic stem cells (Figure 4) come from remaining embryos that come from eggs fertilized in a lab, and are leftover from in vitro fertilization (Zhang, et al., 2006). ESCs express
1 Sperm and egg join
Isolating ES cells
2 Embryo develops for 5-7 days
Blastocyst
4 Grow in dish
Remove inner cell mass
Figure 4: Displays the source of embryonic stem cells as well as
provides a few examples of what types of cells into which the
ESCs can differentiate (leam.genetics.utah.edu). specific transcription factors that act as pluripotency factors to maintain their pluripotent state
(Boyer, et al., 2005). Due to the tendency of ESCs having more accessible chromatin structures,
this allows the embryonic stem cells to turn off certain genes that give it its pluripotent state
(Martello & Smith, 2014). ESCs are highly sought after in the medical field as potential
treatment because it is most advanced in its ability to differentiate into many types of cells.
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Using ESCs for treating spinal cord injuries has shown promise in a couple of patients. Both Kris Boesen and Jake Javier suffered spinal cord injuries that left them paralyzed from the neck down. Both received treatment by receiving an injection of about 10 million AST-OPCi ESCs in the cervical spinal cord (Aldrich, 2016; McCormack, 2016). Since the treatment, Jake has regained some mobility in his hands and is able to write (McCormack, 2016), and Kris is able to use both his hands and his arms, which have allowed him to write, feed himself, and brush his teeth (Aldrich, 2016).
Photograph: Kris Boesen (Iger, 2016)
Photograph: Jake Javier (California Institute for Regenerative Medicine (CIRM), 2016)
Induced pluripotent stem cells (Figure 5) are terminally differentiated cells that have been
reprogrammed to pluripotency. iPSCs do not occur naturally, rather they are produced in the laboratory through the expression of ESC-specific transcription factors, including Oct4, Sox2, cMyc, and Klf4 (Wernig, et al., 2007). The Oct4 and Sox2 are essential for self-renewal; Klf4 is
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essential for reprogramming terminally differentiated cells, and cMyc is important in altering the
chromatin structure (Martello & Smith, 2014).
Creating iPS cells
1 Isolate cells from patient (skin or fibroblasts); grow in a dish
2 Treat cells with
reprogramming factors . ,
r a a 3 Wait a few weeks
4 Pluripotent stem cells
5 Change culture conditions to stimulate cells to differentiate into a variety of cell types
Figure 5: Displays the cells used for induced pluripotent stem
cells as well as the type of cells in which they can differentiate
(1 earn. geneti cs. Utah. edu).
Promising results have been obtained using iPSCs for age-related macular dystrophy (AMD) and inherited macular dystrophy (Best disease-BD); AMD causes visual impairment due to damage of the retinal pigment epithelium (RPE) (Kamao, et al., 2014). Trials in Japan using iPSCs has shown their cell sheet structure is strong enough to withhold transplant procedure, it has been more effective at treating damaged RPE than other treatments, and a relatively small number of iPSCs is required for this treatment (Kamao, et al., 2014). With BD, the use of iPSCs has helped scientists better understand what molecular pathways of the eye are specifically
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damaged, which offers hope that scientists will be able to offer an effective treatment for BD (Singh, et al., 2013)
The two main challenges for use of pluripotent cells in patient therapy are allogenic versus autologous transplant. Patients receiving ESCs as treatment are receiving an allogenic transplant where the cells are not from self, whereas patients receiving iPSCs as treatment are receiving an autologous transplant. An allogenic transplant heightens the chance the donors cells can attack the recipients cells (Medvedev, et al., 2010), which can lead to graft-vs-host disease (GVHD) (Bali, et al., 2016). Patients will have to endure GVHD for the long term, and GVHD is the leading cause of death from allogenic transplant. Steroids and immunosuppressive drugs will have to be regularly taken in order to treat GVHD (Bali, et al., 2016). An autologous transplant puts the patient at less risk because the cells are from self, and should be recognized by the bodys immune system.
The advantage to using ESCs is they do not require reprogramming and therefore, would not risk transdifferentiating into an unwanted cell type. The disadvantages to therapeutic use of ESCs are the possibility of teratoma (tumor) formation and cancer developing caused from a few ESCs remaining undifferentiated (Lee, et al., 2013). Aside from the therapy use, harvesting ESCs requires the destruction of the embryo.
The advantage of using iPSCs does not require the destruction of an embryo. The disadvantage to therapeutic use of iPSCs is the reprogramming. If the cells are not fully reprogrammed, there is a risk of the iPSCs reverting back into their original cell type; or if the iPSCs do not revert back, they can cause mutations in the cell genome that can cause cancerous tumors (Lee, et al., 2013; Medvedev, et al., 2010).
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ETHICS
While there are certainly medical benefits to stem cell research, there is an ethical dilemma: ESC research requires embryo destruction. There is not as much controversy when it comes to other sources of stem cells because the sources come from other organs or adult patients that do not have to be destroyed when collecting the stem cells.
Organization and government guidelines are established because scientists and researchers recognize ESCs come from human embryos. Non-profit organizations, the government, and societal attitudes provide high standards in how to conduct research so there is respect for human life. Therefore, the ethical guidelines provided by the government and a nonprofit organization will be reviewed.
Current Organization Ethical Guidelines
National Academy of Sciences (NAS), a non-profit organization, first set out guidelines for ethical stem cell research supported by private funding in the private industry. These organizations guidelines mostly provide input for ethical research on human ESCs. The NAS guidelines were the first of its kind established during the Bush administration, when there was a lack of ethical standards for ESC research (National Research Council, et al., 2005). Deriving new human ESC lines was not allowed with federal funds, and therefore had no guidelines. Scientists who wanted to research ESCs realized they needed to establish high ethical standards (National Research Council, et al., 2005).
The guidelines set out by the NAS cover research concerning human derived stem cells. These stem cells include embryonic, adult, and induced pluripotent, but there is more detailed guidelines concerning human ESCs because it is more concerned with newly derived ESC lines. The constant involvement of an Embryonic Stem Cell Research Oversight (ESCRO) committee
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in the research process ensures constant ethical research. The ESCRO is not just one committee; rather it is multiple groups of committees formed throughout the United States that ensure ethical research at their respective institutions (National Research Council, et al., 2010). People chosen for this committee are experts in various fields including: developmental and molecular biology, stem cell research, and ethics in human ESC research (National Research Council, et al., 2010). They do not necessarily directly do the research; rather they provide guidance and identify potential problems of the research (National Research Council, et al., 2010). The ESCRO provides oversight of projects involving human ESCs, and are regularly checking in with the researchers and their projects. If a scientist wants to use ESCs, it is required for them to submit their request to the ESCRO committee that includes evidence of Institutional Review Board (IRB) approval (National Research Council, et al., 2010). All research proposals involving nonhuman ESCs only need to be approved by the IRB (National Research Council, et al., 2010). These guidelines help ease public concern and assure the private sectors still perform research responsibly and keep ethics as a high priority.
Most universities have modified the ESCRO committee and now utilize a Scientific Ethics Committee (SEC). An SEC is specifically comprised of individuals that have been involved with the university. For example, at the University of Colorado Anschutz Medical Campus (CU-AMC), the SEC comprises of qualified staff, retirees from CU, and others affiliated with CU. An SEC functions similarly to an ESCRO committee in that they provide oversight and review research proposals involving ESCs. However, their specific purpose is to overview ESC research not regulated by the federal or state governments (Scientific Ethics Committee, 2017).
There are government guidelines provided by the National Institute of Health (NIH) for researchers using federal funds for stem cell research. In 2009, Raynard S. Kington was the
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Acting NIH Director, and involved with the composition and edits of the stem cell research guidelines before they were published (NIH, 2015). These guidelines are modeled after the guidelines set out by the NAS.
To ensure the NIH is continually enforcing the guidelines on researchers, the directors are required to report research progress to the Secretary of Health and Human Services. The Secretary also has an Advisory Committee to the Director that is more directly involved with the NIH. This committee is comprised of individuals hand chosen by the Secretary, and they are chosen based on their expertise in research relevant to what the NIH is involved (NIH, 2015). They are chosen to provide insight on research proposals as well as make sure the researchers are strictly following the guidelines (NIH, 2015). A collective effort by the Secretary, Advisory Committee, and president ensures the NIH guidelines are enforced.
The main guidelines from the NIH lay out restrictions concerning the source from which human ESCs come. NIH funds involving human ESCs are determined for cells derived from the ICM of blastocysts (National Research Council, et al., 2010; Kington, 2009). In order to avoid proactive destruction of human embryos strictly for research, scientists must derive human ESCs from excess embryos resulting from in vitro fertilization that would otherwise be thrown away (National Research Council, et al., 2010; Kington, 2009). These embryos cannot be used unless given documented and informed consent from the donors, and the donors cannot be financially compensated (National Research Council, et al., 2010; Kington, 2009). The NIH has established a registry of ESC lines that are eligible for federally funded research, and scientists are restricted to this registry (Kington, 2009). The NIH registry states whether the embryonic stem cell lines are approved or on hold for research. Additionally, the registry lists the provider and organization that provided the stem cell line (NIH, 2016).
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The majority of the time NIH director decides which stem cell lines are approved for the registry, but some submissions will require additional review from the Advisory Committee to the Director (See Appendix). However, the president also influences the types of ESCs on the registry through his executive order, which will influence the NIH guidelines.
The high standards and strict guidelines a researcher has to overcome to get research approved also better ensures that there is constant ethical research in the government and private sectors, advocating for both federal and private research.
Societal Attitudes on ESC research
Societal attitudes have influenced the guidelines provided by the NIH and NAS. Therefore, it is always helpful to view what societys attitude is for ESC research. This can further ensure updated guidelines for ESC research.
The majority of the public is in support of using ESCs for medical research; the rest are against it (Figure 6). For those in support of ESC research, the reasons why they support it are the following: 1) the medical benefits outweigh the costs 2) the embryos are leftover from IVF and are likely to be thrown away. The potential of finding cures for Alzheimers and Parkinsons disease, and the ability to regain function in limbs influenced peoples decision the most (Bush, 2010). Further, they explained using excess embryos from IVF was a more responsible use of the embryos rather than discarding them (Glick, 2011). For those against ESC research, the predominant reason is because ESC research requires the destruction of the embryo. The majority of those against stem cell research believe the embryo is a person and needs to be protected as such (Glick, 2011). Another reason they are opposed is the possibility the scientific and medical communities are overpromising the treatments that could be developed (Bush,
2010).
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Next, I'm going to read you a list of issues. Regui'dless of whether or not you think it should be legal, for each one, please tell me whether you personally believe that in general it is morally acceptable or morally wrong. How about medical reseai'ch using stem cells obtained from human embryos?
| % Morally acceptable % Morally wrong
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 GALLUP
Figure 6: Displays the approximate percentage of people (dark green) who believe ESC research for medical purposes is morally acceptable versus the percentage of people (light green) who believe it is morally wrong (Gallup, 2016).
POLITICS
The government involvement of establishing NIH guidelines for embryonic stem cell research were mostly expanded during George W. Bushs presidency, and reflect the executive orders of the president. However, Bill Clinton was the first president to make stem cell research more of a forefront issue when he signed an act and amendment that established more government involvement in stem cell research.
In 1993, President Bill Clinton signed the National Institutes of Health Revitalization Act (S-l). This lifted the prohibition on research using fetal tissue from induced abortions, and gave
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the NIH direct funding to research fetal tissue and embryos of IVF that were donated (Office of the Press Secretary, 1993). Additionally, President Bill Clinton also signed the Dickey-Wicker Amendment in 1996, which is still in effect today. This prevented creation or destruction of human embryos for research (Bottum & Anderson, 2008), and further resulted in no federal funding for embryos created or destroyed strictly for research. These legislations drove the decisions made by Bush in his executive order.
Executive Order 13435
In response to the legislations passed by Bill Clinton, in 2001, George Bush allowed federal funding of pluripotent stem cells derived from embryos before August 9, 2001 (Bush, 2010; Office of Legislative Policy and Analysis, 2017). The decision to allow research on already destroyed embryos was the fact that he could not save the lives of those embryos (Bush, 2010). However, he could still save some embryos lives and declared after August 9, 2001, research on additionally derived human ESC lines would not be federally funded.
Under President George Bush, the stem cell research focused on alternative sources for pluripotent stem cells that did not involve deriving new ESC lines. He permitted the Secretary of Health and Human Services to oversee research on all types of cells that could potentially be used as treatment for diseases and other health complications. However, in order to do this research, scientists were not able to derive the cells from creating embryos or from a destroyed or discarded embryo or fetus (National Archives and Records Administration, 2007).
To ensure no confusion for future research, Bush specified the definition of a human embryo. It stated the human embryo was any organism not protected under the 45 CFR 46 regulations from the United States Department of Health & Human Services (DHHS). 45 CFR 46 defines a human subject as a living individual that an investigator can gather data from and
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identify private information (Office for Human Research Protections, 2009). 45 CFR 46 subpart B specifically focuses on protections for pregnant women, human fetuses, and newborns that are involved in research supported by the DHHS (Office for Human Research Protections, 2009).
The NIH could use the DHHS definition of a human subject to argue the embryos did not need to be protected as a human, so the DHHS definition was used to define the difference of a human embryo from a human subject.
In regards to research, the executive order further stated that any technique used on animal cells the researcher wanted to use on the stem cells needed to follow the current law and executive order (National Archives and Records Administration, 2007). Further, the research performed had to prioritize finding treatments for medical needs such as repairing or replacing damaged tissue. At the end of each year, the Secretary was required to report to the president results from research using stem cells during that entire fiscal year. Additionally, the Secretary was to report the advances done on development of pluripotent stem cells derived from sources other than human embryos (National Archives and Records Administration, 2007).
The Secretary of Health and Human Services oversaw the research, and researchers were to answer to the Secretary. Under Bush, the importance of stem cell research was to derive pluripotent stem cells from sources other than embryos (National Archives and Records Administration, 2007). Additionally, the executive order stated the necessity of having moral and ethical standards so that medical research could progress without delays, and allow constant respect of human life and human dignity (National Archives and Records Administration, 2007).
Even though Bush pushed for research on sources other than embryos, there were 60 embryonic stem cell lines on the NIH registry for funded research (Bush, 2010). However, scientists were not satisfied with this amount because 21 ESC lines were viable with which to
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work (NIH, 2001). Even then some of the ESC lines were unusable because of their inability to become undifferentiated or the donor pulled out of the research (NIH, 2001).
In response to Bushs actions, there were proposed acts that covered concerns for both ESC research and other sources of pluripotent stem cells. However, most of these acts were proposed to expand research involving ESCs. This was due to Bushs policies reducing eligible research on ESCs lines.
Legislative Acts Under Bush Presidency
These multiple acts were concerned with expanding research on human ESCs. The Stem Cell Replenishment Act of 2005 (H.R. 162) would have permitted federal funds for research involving human ESCs regardless of when it was derived. Additionally, it gave the NIH permission to review guidelines from 2001, and edit them so that 60 was the minimum amount of stem cell lines that could be used for research (Millender-McDonald, 2005), but this was not enacted. The Stem Cell Research Enhancement Act of 2005 (H.R. 810/S. 471) would have required the Secretary of Human Health Services to allow research on human ESCs. The source of the stem cells would have been 1) excess from in vitro fertilization and donated by the parents 2) prior to be being donated it had to be understood the embryos would never be implanted into a mother 3) the donation had to be recognized by written consent and no financial compensation was received by the donors (Specter, 2005), but the act was vetoed.
These various acts were concerned with using sources other than embryos for stem cells, but none were enacted. The Joe Testaverde Adult Stem Cell Research Act of 2005 (H.R. 2541) would have required the NIH to expand research on adult stem cells. It defined adult stem cells as human stem cells collected from placenta, umbilical cord, or other organs from a living human or a human who died of natural causes (King, 2005). The Respect for Life Pluripotent Stem Cell
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Act of 2005 (H.R. 3144/S. 1557) and Alternative Pluripotent Stem Cell Therapies Enhancement Act of 2006 (S. 2754) would have required researchers to derive pluripotent stem cells without destroying human embryos. Additionally, for H.R. 3144/S. 1557 embryos could not be created for research purposes (Bartlett, 2005; Coburn, 2005; Santorum, 2006).
Some acts were proposed that could have potentially made more people aware of stem cell research like in the Joe Testaverde Adult Stem Cell Research Act of 2005 (H.R. 2541) mentioned above. The Cures Can Be Found Act of 2005 (H.R. 3444) would have given a personal tax credit to individuals to donate funds or umbilical cord blood to facilities that did not do research with embryonic stem cells (Paul, 2005).
George Bush took a side on stem cell research and the country divided in whether any type of stem cell research would be conducted in their states. Some state governments opted to propose amendments for their constitutions and let the people vote on what actions the state would take concerning stem cell research. The following states proposed amendments that would allow federally funded research to take place in their state.
State Amendments
Both Missouri and Michigan proposed amendments to promote embryonic stem cell research. Amendment 2 (Missouri, 2006) and Amendment 08-2 (Michigan, 2008) would have allowed stem cell research, but limited ESC source to 1) the embryos would be discarded anyways 2) no human blastocyst was created solely for research purposes 3) research could not be conducted 14 days after cell division began 4) no person could sell human blastocysts or eggs 5) the blastocysts and eggs had to be voluntarily donated (Ashcroft, 2005; Bean, 2008). Additionally, in Missouri, researchers were required to have their research approved by an oversight committee, and inform the state and local governments of their progress (Ashcroft,
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2005). Despite the states being divided on the issue, both amendments passed, though the decision was closer in Missouri (Ashcroft, 2005).
California added funding of ESC research in addition to deriving new ESC lines without the help of federal funds. Proposition 71 established the California Institute for Regenerative Medicine (CIRM) for providing funds for researchers to be able to conduct research on adult stem cells, cord blood stem cells, and pluripotent stem cells, including human ESCs, but it did not permit human cloning (CA gov, 2004). The ESCs had to come from excess embryos resulting from in vitro fertilization. CIRM provided continual funding for ESC research independent of federal funds or executive orders. The funding for the stem cell research came from general obligation bonds; Proposition 71 started with $3 billion in general obligation bonds (CA gov, 2004). General obligation bonds are debt securities issued by the state government to fund programs that may not bring in revenue. The money for these bonds is attained through income, sales, and/or property taxes. Oversight of ESC research was provided by an Independent Citizens Oversight Committee (ICOC), which required yearly progress reports on ESC research (CA gov, 2004).
The actions done by the states mentioned above revealed that the federal governments power over this issue could be limiting. If states do not agree with the executive orders, then they have the ability to take action. In this instance, if more states take action to fund stem cell research without federal help and make great progress in research, more states may follow their lead. The federal government might then be forced to adopt the same stance on stem cell research as the successful states.
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Executive Order 13505
Under President Barack Obama, the stem cell research expanded to using human embryonic and human non-embryonic stem cells. Like Bushs executive order, Obama recognized the positive potential treatments stem cells offer. Obama differed from Bush in that he allowed research to include human ESCs, and new ESC line derivations (National Archives and Records Administration, 2009).
Obama stated what type of stem cell research could be conducted. Again, it was similar to Bushs executive order that permitted research done as long as it followed NIH and/or NAS guidelines. However, Obama allowed research to be done on human ESCs and allowed new ESC derivations (National Archives and Records Administration, 2009).
The executive order further stated that the NIH had laid out guidelines as to what was appropriate stem cell research. With this new executive order, it recognized that the Secretary of Health and Human Services would review these guidelines, and update them to match the new changes Obama made for stem cell research (National Archives and Records Administration, 2009).
Bush limited federal funding on research involving human ESCs, but Obama permitted federal funding for research involving these cells (National Archives and Records Administration, 2009). There were 384 ESC lines that were available on the NIH registry for funded research (NIH, 2016), which was a drastic expansion since Bushs presidency. Obamas executive order is currently enacted.
Legislative Acts Under Obama Presidency
The first act is concerned with research using ESCs and was specifically proposed to amend a previous act. The Stem Cell Research Advancement Act of 2013 (H.R. 2433) would
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require the Secretary of Health and Human Services to direct research that uses all types of human stem cells, including ESCs (DeGette, 2013). It lays out the requirements that need to be met for research of human ESCs. These requirements include: 1) the embryos are in excess from in vitro fertilization and are not going to be used 2) are voluntarily donated by the parents with written documentation where the parents received no financial compensation (DeGette, 2013). Additionally, it specifically states no finances may be used in support of research involving human cloning (DeGette, 2013). This act was referred to the Subcommittee on Health (DeGette, 2013).
The second act uses tax credit as an incentive to avoid research with ESCs. The Ethical Stem Cell Research Tax Credit Act of 2015 (S. 43) would allow a 30% tax credit from the Internal Revenue Code for expenses on research involving developing techniques to derive and test potential stem cells that may treat disease or other health complications, but is not allowed for corporations (Vitter, 2015). This tax credit would not be granted to research expenses that involve 1) creating a human embryo for research 2) destroying, throwing out, or injuring a human embryo 3) performing any prohibited research using stem cells (Vitter, 2015). This act has been referred to the Committee of Finance (Vitter, 2015).
While politics are used to influence ESC research, our countrys people exhibit religious diversity that influences their decisions. The government leaders are no exception, and personal religion can play a major role in influencing certain political decisions, and this was apparent when George W. Bush issued his executive order.
Religious Influence on Bushs Executive Order
Bushs actions were greatly impacted by his Evangelical Christian belief. In the Christian faith, life begins at conception. God has deemed all human life sacred, since all human beings
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are created in His image (Hanegraaff, 2008). Bush was adamant about incorporating this belief into his policies, and wanted them to reflect that human life was sacred because God created each person in His image (Bush, 2010). Bush was not against the use of stem cells for research or therapy, but was against destroying embryos as a source for stem cells. He empathized with the potential new medical benefits human ESCs had to offer because he had lost a sister to leukemia when she was young, but he also wanted to respect moral boundaries (Bush, 2010). His policies did not support isolation of new human ESC lines because of the moral dilemma of proactively ending a life to save a life (Bush, 2010). He was not against the use of stem cells for research or therapy so long as the source of the stem cells was not from human embryos. In issuing an executive order that allowed stem cell research on alternative sources to embryos, Bush was able to support science without violating his Christian beliefs.
PERSONAL VIEW
My Christian faith plays an integral role in why I support research using alternative sources of stem cells. I believe that life begins at conception and I cannot disregard the sanctity of human life. With that belief comes my conviction that one human life cannot be harmed at the expense of another human life, even though there are potential medical benefits. I personally have a problem with using excess embryos from in vitro fertilization for research despite the likelihood that those embryos will be thrown away. These embryos have the potential of forming into a human. Because they have the potential of being a human, I do not support proactively ending life. I do not believe stem cell research should stop altogether; rather, the focus should be on alternative sources to ESCs.
I am fully aware of the advantages ESCs have to offer for advancing treatment. Kris Boesen was able to regain the ability to use his arms and his hands through the administration of
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ESCs into his spinal cord (Aldrich, 2016). I have an uncle who has Parkinsons disease and I recognize how he could be positively impacted. However, just because there are potential medical benefits, this does not validate the destruction of embryos.
Continued research on alternative pluripotent sources may cause scientists to discover new potential that has not yet been seen. As reprogramming technology improves to complete reprogramming, iPSCs may become a viable treatment. My further support for iPSCs is the hope that an allogenic transplant will no longer be necessary, and therefore deaths caused by GVHD could be reduced.
I realize that even though I oppose ESC research, it is not going to be terminated. Therefore, I believe organizations like the NIH and NAS are vital in ensuring ethical research, and the publics opinion is crucial in keeping guidelines updated. Even with the strict guidelines, there remains a potential for ethical abuse so I am a proponent of scientific ethics committees in private research to discourage ethical abuse. I would also like to see more use of scientific ethics committees in government research.
Because research with adult stem cells and iPSCs are less controversial, policies that are established need not change with each new president. Thus, the ethical issues which typically involve the more controversial ESCs could be avoided. Further, since states are already setting stem cell policies, it may be beneficial to allow states to lead the way. This means less federal government involvement and less government bureaucracy could pave the way for quicker progress in research. I do not agree with the CIRM, but it has allowed continual research despite presidential changes.
Being a biology major and a hopeful health care provider, my goal is to help all people, especially those that are helpless. All life is sacred and deserves to be protected. I believe stem
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cell research is highly important; religious, ethical, and political views do not have to inhibit scientific progress. However, by focusing on adult stem cells and iPSCs, we can all come together to continue to better medicine in the United States.
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Appendix
O
HESCREGISTRY (NIH/OD)
Reply all | v
Mon 4/17, 7:54 AM Kayla O'Quinn: +1 more ¥
Action Items
G
Dear Ms. O'Quinn,
Thank you for your interest in stem cell research.
The National Institutes of Health (NIH) issued the NIH Guidelines for Human Stem Cell Research (Guidelines) on July 7, 2009. The Guidelines list the criteria for the NIH Director to determine the eligibility for use of specific human embryonic stem cell (hESC) lines in NIH-funded research.
All hESC line submissions that are eligible for review under the Guidelines are ushered into the review process shortly after they are received. There is no standard turnaround time for these reviews and each submission is evaluated individually according to the requirements of the Guidelines. Often the submissions require additional information from the submitter before a final decision can be issued and this can add time to the review process. Furthermore, some submissions require review by the Advisory Committee to the Director, NIH.
The current list of approved lines can be found on the NIH Human Embryonic Stem Cell Registry.
Sincerely,
Aparna Singh
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HESCREGISTRY (NIH/OD)
*? Reply all | v
Mon S/1, 8:30 AM Kayla O'Quinn; +1 more V
Dear Ms. O'Quinn,
As mentioned in my previous email, the NIH Guidelines for Human Stem Cell Research (Guidelines), list the criteria for the NIH Director to determine the eligibility for use of specific human embryonic stem cell (hESC) lines in NIH-funded research. The owners of the hESC lines submit information pertinent to the Guidelines requirements.
The Guidelines focus on the embryo donation process and require that all human embryonic stem cell lines used in NIH-funded research must be: 1) derived from embryos created by in vitro fertilization (IVF) for reproductive purposes and no longer needed for those purposes, and 2) from embryos donated by the individual(s) who sought reproductive treatment and who gave voluntary, written informed consent.
The Guidelines also prohibit using hESCs derived from other sources, including: somatic cell nuclear transfer, parthenogenesis, and embryos created by IVF for research purposes.
Sincerely,
Aparna Singh
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Full Text

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Science, Politics, and Religion: The Ethical Dilemma of Embryonic Stem Cell Research An undergraduate thesis submitted in partial completion of the M etropolitan State University of D enver Honors Program May 5, 2017 Dr. Vida Melvin Dr. Sheila Rucki Dr. Megan Hughes Zarzo Primary Advisor Second Reader Honors Program Director

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 1 Science, Politics, and Religion: The Ethical Dilemma of Embryonic Stem Cell Research Kayla O'Quinn Metropolitan State University of Denver

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 2 INTRODUCTION The purpose of this study is to further investigate all the types of human stem cells potentially available for research purposes: adult stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) In addition to researc h, this study will highlight the advanta ges and disa dvantages of using each type o f stem cell. For example, a disadvantage of using ESCs elicits great risk because it requires an allogenic transplant This can lead to the death of a patient from graft vs host disease, where the immune system is constantly compromised. However, the use of stem cells goes deeper than just the scientific surface; stem cells cross over mu ltiple disciplines. T he politics, e thics, and religious influences a lso play a part in the progress of stem cell research. First, p olitics elicit discontinuity of stem cell research because of leadership change. Therefore, some states take action to determine whether stem cell research can occur and their actions may encourage stem cell research to become state mandated. Second, e th ics causes controversy for ESC research because it requires destruction of an embryo To combat the controversy, organizations have been established in the governmental and private arenas that promote ethical research However, it may not be enough. Ethics may lead to r estricted research with adult stem cells and iPSCs Finally, r eligion influences may shape our society's views on the type of stem cells used in research as seen in Bush's executive order. Most often politics, ethics, and religion conflict with research involving ESCs. The constant battle that ensues working with ESCs may never be resolved. However, even with all these disciplines influencing ESC research, medical progress can still be achieved through the use of adult stem cells and iPSCs

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 3 PREIMPLANTATION DEVELOPMENT Fertilization is when the sperm penetrates the egg producing the zygote that contains genetic material from both parents. Within 24 hours of fertilizatio n the zygote begins to divide. All the cells of the embryo are derived from the zygote and must undergo cellular division as it develops to produce numerous cells. Thes e cells become many different types of cells through differentiation. When cells differentiate, they are becoming more specialized cell types and display more specific functions (Figure 1, Kumar, et al., 2010) For example, a cardiomyocyte is a heart cell tha t allows the heart to contract At the 4 cell stage the embryo becomes spherically shaped and is called a morula (Figure 2 square d4 ) (Niakan, et al., 2012). T he cells of the morula are totipotent, meaning the y are able Figure 1: Displays the different potencies of stem cells as well as the organs into which pluripotent stem cells can differentiate (Kumar, et al., 2010).

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 4 to diffe rentiate into all cells of the embryo (Khanlarkhani, et al., 2016); this includes all embryonic structures as well as extraembryonic structures like the placenta and amniotic sac. At the 16 cell stage the morula forms a central cavity (Figure 2, square d4) and the embryo is th en called a blastocyst (Figure 2 square d5). The b lastocyst consists of two cell populations: the outer cells are the trop hectoderm and the inner cells are the inner cell mass (ICM). T he cells of the ICM are considered pluripotent and can differentiate into all cell types of the e mbryo (Hanna, et al., 2010), while the trophectoderm is able to differentiate into extraembryonic structures (Yu & Thomson, 2008). The cells of the ICM are the source of e mbryonic stem cells for use in r esearch and therapy because th ey are able to differentiate into various types of organs (Kumar, et al., 2010)

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 5 STEM CELLS A stem cell is able to self renew and has the ability to produce differentiated cell types (Jaenisch & Young, 2008). During cellular division, stem cells produce two daughter cells where on e daughter cell remains as a stem cell for self renewal; the other daughter cell will differentiate Figure 2: Following fertilization, the embryo undergoes cell divisions; d0 d3 displays the cell divisions. At d4, the cells compact and form the morula; the zona pelluc ida is around the morula to serve as a barrier around the embryo. At d5, the blastocyst as formed. The white arrow to pointing to the inner cell mass. By d6, the blastocyst emerges from the zona pellucida, and by d7 the embryo is ready to implant on the ut erus (Niakan, et al., 2012).

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 6 (Martello & Smith, 2014). Because of their ability to self new and differentiate, research involving adult stem cells, embryonic stem cells ( ESCs ) and induced pluripotent stem cells ( iPSCs ) is significant in advancing the medical field. These cells provide repair for damaged tissu e, and regenerate new cells affected by disease. Stem cells are categorized by developmental potential and their source. Mos t adult stem cells are multipotent and have the capability to differentiate into several different cells types depending on the tissue of origin. ESCs and iPSCs have the most developmental potential, because they have the capability to differenti ate into a ny cell type of the embryo. Adult stem cells are already highl y utilized in the medical field b ecause t hey have been used the longest in therapy, and were first used for a bone marrow transplant in the 1950s (Jansen, 2005). Figure 3: Displays the sources of somatic stem cells also known as adult stem cells. These cells reside in their specific niche (learn.genetics.utah.edu).

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 7 A dult stem cells (Figure 3) reside in differentiated tissue, but are undifferentiated cells. These cells are used to maintain and repair the tissue in which they reside. Adult stem cells can be d erived from various sources, including dental pulp, which is in the center of a tooth and contains odontoblasts (Laino, et al., 2006), bone marrow, adipose tissue or fat cells, skeletal muscles, epithelial tissue or skin cells of various organs like the lung, retina, ovaries, and testis (Mimeau lt & Batra, 2008). The disadvantage of using adult stem cells is the limited potency for which they display. This restricts the areas where they can be transplanted, and they can only be used as treatment for cells that they can produce For example, hemat opoetic stem cells can only produce blood cells, and are unable to pro duce neurons or cardiomyocytes. A specific type of adult stem cell, the hematopoietic stem cells can be used as treatment for blood diseases like leukemia (Hosseini, et al., 2016). Bren den Whittaker had a genetic disease that caused a malfunctioning immune system, and Evangelina Padilla Vaccaro was diagnosed with severe combined immunodeficiency that resulted in a non functioning immune system. Both received Photograph: Brenden Whittaker and Evangelina Padilla Vaccaro (California Institute for Regenerative Medicine (CIRM), 2016)

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 8 treatment that removed their own blood stem cells The blood stem cells were genetically modified and re infused into their bodies, resulting in new blood and fully functional immune systems ( CIRM, 2016). Embryonic stem cells (Figure 4) come from remaining embryos that come from eggs fertilized in a lab, and are leftover from in vitro fertilization (Zhang et al., 2006). ESCs express specific transcription factors that act as "pluripotency factor s" to maintain their pluripotent state (Boyer, et al., 2005). Due to the tendency of ESCs having more accessible chromatin structures, this allows the embryonic stem cells to turn off certain genes that give it its pluripotent state (Martello & Smith, 2014). ESCs are highly sought after in the medical field as potential treatment because it is most advanced in its ability to differentiate into many types of cells. Figure 4: Displays the source of embryonic stem cells as well as provides a few examples of what types of cells into which the ESCs can differentiate (learn.genetics.utah.edu).

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 9 Using ESCs for treating spinal cord injuries has shown promise in a couple of patients. Both Kris Boesen and Jake Javier suffered spinal cord injuries that left them paralyzed from the neck down. Both received treatment by receiving an injection of about 10 million AST OPC 1 ESCs in the cervical spinal cord (Aldrich, 2016; McCormack, 2016). Since the treatment, Jake has regained some mobility in his hands and is a ble to write (McCormack, 2016), and Kris is able to use b oth his hands and his arms, which have allowed him to write, feed himself, and brush his teeth (Aldrich, 2016). Induced pluripotent stem cells (Figure 5) are terminally differentiated cells that have been reprogrammed to pluripotency iPSCs do not occur naturally ra ther they are produced in the laboratory through the e xpression of ESC specific transcription factors, including Oct4, Sox 2, cMyc, and Klf4 (Wernig, et al., 2007). The Oct4 and Sox2 are essential for self renewal; Klf4 is Photograph: Kris Boesen (Iger, 2016) Photograph: Jake Javier (California Instit ute for Regenerative Medicine (CIRM), 2016)

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 10 essential for reprogramming terminally differentiated cells and cMyc is important in altering the chromatin structure (Martello & Smith, 2014). Promising results have been obtained using iPSCs for age related macular dystrophy (AMD) and inherited macular dystrophy (Be st disease BD); AMD causes visual impairment due to damage of the retinal pig ment epithelium (RPE) (Kamao et al., 2014). Trials in Japan usin g iPSCs has shown their cell sheet structure is strong enough to withhold transplant procedure, it has been more effective at treating damaged RPE than other treatments, and a relatively small number of iPSCs is requir ed for this treatment (Kamao et al., 2014). With BD, the use of iPSCs has helped scientists better understand what molecular pathways of the eye are specifically Figure 5: Displays the cells used for induced pluripotent stem cells as well as the type of cells in which they can differentiate (learn.genetics.utah.edu).

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 11 damaged, which offers hope that scientists will be able to offer an effec tive treatment for BD (Singh et al., 2013) The two main c hallenges for use of pluripotent cells in patient therapy are allogen ic v ersu s autologous transplant. Patients receiving ESCs as treatment are receiving an allogenic transplant where the cells are not from self whereas patients receiving iPSCs as treatment are receiving an autologous transplant. An allogenic transplant heightens th e chance the donor's cells can attack the recipient's cells (Medvedev, et al., 2010), which can lead to graft vs host disease (GVHD) (Bali, et al., 2016). Patients will have to endure GVHD for the long term, and GVHD is the leading cause of death from allogenic transplant. Steroids and immunosuppressive drugs will have to be regularly taken in order to treat GVHD (Bali, et al., 2016). An autologous transplant puts the patient at less risk because the cells are from self, and should be recognized by the body's immune system. The advantage to using ESCs is they do not require reprogramming and therefore, would not risk transdifferentiati ng into an unwanted cell type. The disadvantages to therapeutic use of ESCs are the possibility of teratoma (tumor) formation and cancer developing caused from a few ESCs remaining undifferentiated (Lee, et al., 2013) Asi de from the therapy use, harvestin g ESCs requires the destruction of the embryo. The advantage of using iPSCs does not require the destruction of an embryo. The disadvantage to therapeutic use of iPS Cs is the reprogramming If the cells are not fully reprogrammed, there is a risk of the i PSCs reverting back into their original cell type ; or if the iPSCs do not revert back, they can cause mutations in the cell genome that can cause cancerous tumors ( Lee, et al., 2013; Medvedev, et al., 2010)

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 12 ETHICS While there are certainly medical benefits to stem cell research, there is an ethical dilemma : ESC research requires embryo destruction There is not as much controversy when it comes to other sources of stem cells because the sources come from other organs or adult patients that do not ha ve to be destroyed when collecting the stem cells. Organization and government guidelines are established because scientists and researchers recognize ESCs come from human embryo s. Non profit organizations, the government and societal attitudes provide high standards in how to conduct research so there is respect for human life. Therefore, the ethical guidelines provided by the government and a non profit organization will be reviewed. Current Organization Ethical Guidelines National Academy of Sciences (NAS) a non profit organization, first set out guidelines for ethical stem cell research supported by private funding in the private industry. These organization's guidelines mostly provide input for ethical resea rch on human ESC s. The NAS guidelines wer e the first of its kind established during the Bush administration, when there was a lack of ethical standards for ESC research (National Research Council, et al., 2005). Deriving new human ESC lines was not allowed with federal funds, and there fore had no guidelines. S cientists who wanted to research ESCs realized they needed to establish high ethical standard s (National Research Council, et al., 2005). The guidelines set out by the NA S cover research concerning human derived stem cells. These stem cells include embryonic, adult, and induced pluripotent, but there is more detailed guidelines concerning human ESCs because it is more concerned with newly derived ESC lines T he constant involvement of an Embryonic Stem Cell Research Oversight (ESCRO) committe e

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 13 in the research process ensures constant ethical research. The ESCRO is not just one committee; r ather it is multiple groups of committees formed throughout the United States that ensure ethical research at their respective institutions ( National Researc h Council, et al., 2010 ). People chosen for this committee are experts in various fields including: developmental and molecular biology, stem cell research, and ethics in human ESC research ( National Research Council, et al., 2010 ). They do not necessarily directly do the research; rather they provide guidance and identify potential problems of the research ( National Research Council, et al., 2010 ). The ESCRO provide s oversight of projects involving human ESCs, and are regularly checking in with the researc hers and their projects. If a scientist wants to use ESCs, it is required for them to submit their request to the ESCRO committee that includes evidence of Institutional Review Board (IRB) approval ( National Research Council, et a l., 2010 ). All research pr oposals involving non human ESCs only need to be approved by the IRB ( National Research Council, et al., 2010). These guidelines help ease public concern and assure the private sectors still perform research responsibly and keep ethics as a high priority. Most universities have modified the ESCRO committee and now utilize a Scientific Ethics Committee (SEC). An SEC is specifically comprised of individuals that have been involved with the university. For example, at the University of Colorado Anschutz Medic al Campus (CU AMC ), the SEC comprises of qualified staff, retirees from CU, and others affiliated with CU. An SEC functions similarly to an ESCRO committee in that they provide oversight and review research proposals involving ESCs However, their specific purpose is to overview ESC research not regulated by the federal or state governments (Scientific Ethics Committee, 2017) There are government guidelines provided by the National Institute of Health (NIH) for researchers using federal funds for stem cel l research. In 2009, Raynard S. Kington was the

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 14 Acting NIH Director, and involved with the composition and edits of the stem cell research guidelines before they were published (NIH, 2015). These guidelines are modeled after the guidelines set out by the N AS. To ensure the NIH is continually enforcing the guidelines on researchers, the directors are required to report research progress to the Secretary of Health and Human Services. The Secretary also has an Advisory Committee to the Director that is more direct ly involved with the NIH. This c ommittee is comprised of individuals hand chosen by the Secretary, and they are chosen based on their expertise in research relevan t to what the NIH is involved (NIH, 2015). They are chosen to provide insight on resear ch proposals as well as make sure the researchers are strictly followin g the guidelines (NIH, 2015). A collective effort by the Secretary, Advisory Committee, and president ensures the NIH guidelines are enforced. The main guidelines from the NIH lay out restrictions concerning the source from which human ESCs come. NIH funds involving human ESCs are determined for cells derived from the ICM of blastocysts ( National Research Council, et al., 2010 ; Kington, 2009). In order to avoid proactive destruction of human embryos strictly for research, scientists must derive human ESCs from excess embryos resulting from in vitro fertilization that would otherwise be thrown away ( National Research Council, et al., 2010 ; Kington, 2009). These embryos cannot be used unle ss given documented and informed consent from the donors, and the donors cannot be financially compensated ( National Research Council, et al., 2010 ; Kington, 2009). The NIH has established a registry of ESC lines that are eligible for federally funded research, and scientists are restricted to this registry (Kington, 2009). The NIH registry states whether the embryonic stem cell lines are approved or on hold for resea rch. Additionally, the registry lists the provider and organization that provided the stem cell line (NIH, 2016).

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 15 The majority of the time NIH director decides which stem cell lines are approved for the registry, but some submissions will require addition al review from the Advisory Committee to the Director ( See Appendix ). However, the president also influences the types of ESCs on the registry through his executive order, which will influence the NIH guidelines. The hi gh standards and strict guidelines a researcher has to overcome to get research approved also better ensures that there is constant ethical research in the government and private sectors, advocating for both federal and private research Societal Attitudes on ESC research Societal attitud es have influenced the guidelines provided by the NIH and NAS. Therefore, it is always helpful to view what society's attitude is for ESC research. This can further ensure updated guidelines for ESC research. The majority of the public is in support of us ing ESCs for medical research; the rest are against it (Figure 6). For those in support of ESC research, the reasons why they support it are the following: 1) the medical benefits outweigh the costs 2) the embryos are leftover from IVF and are likely to be thrown away. The potential of finding cures for Alzheimer's and Parkinson's disease, and the ability to regain function in limbs influenced people's decision the most (Bush, 2010). Further, they explained using excess embryos from IVF was a more responsib le use of the embryos rather than discarding them (Glick, 2011). For those against ESC research, the p redominant reason is because ESC research requires the destruction of the embryo. The majority of those against stem cell research believe the embryo is a person and needs to be protected as such (Glick, 2011). Another reason they are opposed is the possibility the scientific and medical communities are overpromising the treatments that c ould be developed (Bush, 2010).

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 16 POLITICS The government involvement of establishing NIH guidelines for embryonic stem cell research were mostly expanded during George W. Bush's presidency, and reflect the executive orders of the president. However, Bill Clinton was the first president to make stem cell research more of a for e front issue when he signed an act and a mendment that established more government involvement in stem cell research. In 1993, President Bill Clinton signed the National Institutes of Health Revitalization Act (S 1) This lifted the prohibition on research using fetal tissue from induced abortions, and gave Figure 6: Displays the approximate percentage of people (dark green) who believe ESC research for medical purposes is morally acceptable versus the percentage of people (light green) who believe it is morally wrong (Gallup, 2016).

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 17 the NIH direct funding to research fetal ti ssue and embryos of IVF that were donated (Office of the Press Secretary, 1993). Additionally, President Bill Clinton also signed the Dickey Wicker Amendment in 1996, which is still in effect today. This prevented creation or destruction of human embryos for rese arch (Bottum & Anderson, 2008), and further resulted in no federal funding for embryos created or destroyed strictly for research. These legislations drov e the decisions made by Bush in his executive order. Executive Order 13435 In response to the legislations passed by Bill Clinton, in 2001, George Bush allowed federal funding of pluripotent stem cells derived from embryos before August 9, 2001 (Bush, 201 0; Office of Legislative Policy and Analysis, 2017). The decision to allow research on already destroyed embryos was the fact that he could not save the lives of those embryos (Bush, 2010). However, he could still save some embryos lives and declared afte r August 9, 2001, research on additionally d erived human ESC lines would not be federally funded Under President George Bush, the stem cell research focused on alternative sources for pluripotent stem cells that did not involve deriving new ESC lines He permitted the Secretary of Health and Human Services to oversee research on all types of cells that could potentially be used as treatment for diseases and other health complications. However, in order to do this research, scientists were not able to deri ve the cells from creating embryos or from a destroyed or discarded embryo or fetus (National Archives and Records Administration, 2007). To ensure no confusion for future research, Bush spec ified the definition of a human embryo. It stated the human embr yo was any organism not protected under the 45 CFR 46 regulations from the United States Department of Health & Human Services (DHHS). 45 CFR 46 defines a human subject as a living individual that an investigator can gather data from and

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 18 identify private i nformation (Office for Human Research Protections, 2009). 45 CFR 46 subpart B specifically focuses on protections for pregnant women, human fetuses, and newborns that are involved in research supported by the DHHS (Office for Human Research Protections, 20 09). The NIH could use the DHHS definition of a human subject to argue the embryos did not need to be protected as a human, so t he DHHS definition was used to define the difference of a human embryo from a human subject. In regards to research, the execut ive order further stated that any technique used on a nimal cells the researcher wanted to use on the stem cells needed to follow the current law and executive order (National Archives and Records Administration, 2007). Further, the research performed had t o prioritize finding treatments for medical needs such as repairing or replacing damaged tissue. At the end of each year, the Secretary was required to report to the president results from research using stem cells during that entire fiscal year. Additiona lly, the Secretary was to report the advances done on development of pluripotent stem cells derived from sources other than human embryos (National Archives and Records Administration, 2007). The Secretary of Health and Human Services oversaw the research and researchers were to answer to the Secretary. Under Bush, the importance of stem cell research was to derive pluripotent stem cells from sources other than embryos (National Archives and Records Administ ration, 2007). Additionally, the executive order stated the necessity of having moral and ethical standards so that medical research could progress without delays and allow constant respect of human life and human dignity (National Archives and Records Administration, 2007). Even though Bush pushed fo r research on sources o ther than embryos, there were 60 embryonic stem cell lines on the NIH registry for funded research (Bush, 2010) However, scientists were not satisfied with this amount because 21 ESC lines were viable with which to

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 19 work (N IH, 2001 ). Even then some of the ESC lines were unusable because of their inability to become undifferentiated or the donor pulled out of the research (NIH, 2001). In response to Bush's actions, there were proposed acts that covered concerns for both ESC research and other sources of pluripotent stem cells. However, most of these acts were proposed to expand research involving ESCs. This was due to Bush's policies reducing eligible research on ESCs lines Legislative Acts Under Bush Presidency These multiple acts were concerned with expanding research on human ESCs. The Stem Cell Replenishment Act of 2005 (H.R. 162) would have permitted federal funds for research involving human ESCs regardless of when it was derived. Additionally, it gave the NIH permission to re view guidelines from 2001, and edit them so that 60 was the minimum amount of stem cell lines that could be used for research ( Millender McDonald, 2005 ), but this was not enacted. The Stem Cell Research Enhancement Act of 2005 (H.R. 810/S. 471) would have required the Secretary of Human Health Services to allow resear ch on human ESCs The source of the stem cells would have been 1) excess from in vitro fertilization and donated by the parents 2) prior to be being donated it had to be understood the embryos would never be implanted into a mother 3) the donation had to be recognized by written consent and no financial compensation was received by the donors ( Specter, 2005 ), but the a ct was vetoed. These various acts were concerned with using sources other tha n embryos for stem cells but none were enacted The Joe Testaverde Adult Stem Cell Research Act of 2005 (H.R. 2541) would have required the NIH to expand research on adult stem cells. It defined adult stem cells as human stem cells collected from placenta umbilical cord, or other organs from a living human or a human who died of natural causes ( King, 2005 ). The Respect for Life Pluripotent Stem Cell

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 20 Act of 2005 (H.R. 3144/S. 1557) and Alternative Pluripotent Stem Cell Therapies Enhancement Act of 2006 (S. 2754) would have required researchers to derive pluripotent stem cells without destroying human embryos. Additionally, for H.R. 3144/S. 1557 embryos could not be created for research purposes ( Bartlett, 2005; Coburn, 2005; Santorum, 2006 ). Some acts wer e proposed that could have potentially made more people aware of stem cell research like i n the Joe Testaverde Adult Stem Cell Research Act of 2005 (H.R. 2541) mentioned above. The Cures Can Be Found Act of 2005 (H.R. 3444) would have given a personal tax credit to individuals to donate funds or umbilical cord blood to facilities that did not do research with embryonic stem cells ( Paul, 2005 ). George Bush took a side on stem cell research and the country divided in whether any type of stem cell research wo uld be conducted in their states. Some state governments opted to propose amendments for their constitutions and let the people vote on what actions the state would take concerning stem cell research. The following states proposed amendments that would all ow federally funded research to take place in their state. State Amendments Both Missouri and Michigan proposed amendments to promote embryonic stem cell research Amendment 2 (Missouri, 2006) and Amendment 08 2 (Michigan, 2008) would have allowed stem cell research but limited ESC source to 1) the embryos would be discarded anyways 2) no human blastocyst was created solely for research purposes 3) research could not be conducted 14 days after cell division began 4) no person could sell human blas tocysts or eggs 5) the blastocysts and eggs had to be voluntarily donated (Ashcroft, 2005; Bean, 2008). Additionall y, in Missouri, researchers were required to have their research approved by an oversight committee, and inform the state and local governmen ts of their progress (Ashcroft,

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 21 2005). Despite the states being divided on the issue, both amendments passed though the decision was closer in Missouri (Ashcroft, 2005) California added funding of ESC research in addition to deriving new ESC lines with out the help of federal funds. Proposition 71 established the California Institute for Rege nerative Medicine (CIRM) for providing funds for researchers to be able to conduct research on adult stem cells, cord blood stem cells, and pluripotent stem cells, including h uman ESC s, but it did not permit human clo ning (CA gov, 2004). The ESCs had to come from excess embryos resulting from in vitro fertilization. CIRM provided continual funding for ESC research independent of federal fu nds or executive orders. The funding for the stem cell research came from general obligation bonds; Proposition 71 started with $3 billion in general obligation bonds (CA gov, 2004). General obligation bonds are debt securities issued by the state governme nt to fund programs that may not bring in revenue. The money for these b onds is attained through income, sales, and/or property taxes. Oversight of ESC research was provided by an Independent Citiz en's Oversight Committee (ICOC), which required yearly prog ress reports on ESC research (CA gov, 2004). The actions done by the states mentioned above revealed that the federal government's power over this issue could be limiting. If states do not agree with the executive orders, then they have the ability to ta ke action In this instance, if more states take action to fund stem cell research without federal help and make great progress in research more states may follow their lead. The federal government might then be forced to adopt the same stance on stem cel l research as the successful states.

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 22 Executive Order 13505 Under President Barack Obama, the stem cell research expanded to using human embryonic and human non embryonic stem cells. Like Bush's e xecutive order, Obama recognized the positive pote ntial t reatments stem cells offer. Obama differed from Bush in that he allowed research to include human ESCs, and new ESC line derivations (National Archives and Records Administration, 2009). Oba ma stated wha t type of stem cell research could be conducted. Aga in, it wa s similar to Bus h's executive order that permitted research done as long as it followed NIH and/or NAS g uidelines. However, Obama allowed research to be done on human ESCs and allowed new ESC derivations (National Archives and Records Administration, 2009). Th e executive order further stated that the NIH had l aid out g uidelines as to what was appropriate stem cell research. With this new executive order, it recognized that the Secretary of Health and Huma n Services would review these guidelines, and update them to match the new changes Obama made for stem cell research (National Archives and Records Administration, 2009). Bush limited f ederal funding on research involving h uman ESCs, but Obama permitted f ederal funding for research involving these cells (National Archives and Records Admin istration, 2009). There were 384 ESC lines that were available on the NIH registry for funded research (NIH, 2016) which was a drastic expansion since Bush's presidency Obama's executive order is currently enacted. Legislative Acts Under Obama Presidency The first act is concerned with research using ESCs and was specifically proposed to amend a previous act The Stem Cell Research Advancement Act of 2013 (H.R. 2433) w ould

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 23 require the Secretary of Health and Human Services to direct research that uses all types of human stem cells, including ESCs (DeGette, 2013). It lays out the requirements that need to be met for research of human ESCs. These requirements include: 1) the embryos are in excess from in vitro fertilization and are not going to be used 2) are voluntarily donated by the parents with written documentation where the parents received no financial compensation (DeGette, 2013). Additionally, it specifically stat es no finances may be used in support of research involving human cloning (DeGette, 2013). This act was referred to the Subcommittee on Health (DeGette, 2013). The second act uses tax credi t as an incentive to avoid research with ESCs. The Ethical Stem C ell Research Tax Credit Act of 2015 (S. 43) would allow a 30% tax credit from the Internal Revenue Code for expenses on research involving developing techniques to derive and test potential stem cells that may treat disease or other health complications, b ut is not allowed for corporations (Vitter, 2015). This tax credit would not be granted to research expenses that involve 1) creating a human embryo for research 2) destroying, throwing out, or injuring a human embryo 3) performing any prohibited research using stem cells (Vitter, 2015). This act has been referred to the Committee of Finance (Vitter, 2015). While politics are used to influence ESC research, our country's people exhibit religious diversity that influences their decisions. The government lea ders are no exception, and personal religion can play a major role in influencing certain political decisions, and this was apparent when George W. Bush issued his executive order. Religious Influence on Bush's Executive Order Bush's actions were greatly impacted by his Evangelical Christian belief. In the Christian faith, life begins at conception. God has deemed all human life sacred, since all human beings

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 24 are created in His image (Hanegraaff, 2008). Bush was adamant about incorporating this belief into his policies, and wanted them to reflect that human life was sacred because God created each person in His image (Bush, 2010). Bush was not against the use of stem cells for research or therapy, but was against destroying embryos as a source for stem cell s He empathized with the potential new medical benefits human ESCs had to offer because he had lost a sister to leukemia when she was young, but he also wanted to respect moral boundaries (Bush, 2010). His policies did not support isolation of new human ESC lines because of the moral dilemma of proactively ending a life to save a life (Bush, 2010). He was not against the use of stem cells for research or therapy so long as the source of the stem cells was not from human embryos. In issuing an executive or der that allowed stem cell research on alternative sources to embryos, Bush was able to support science without violating his Christian beliefs. PERSONAL VIEW M y Christian faith plays an integral role in why I support research using alternative sources o f stem cells. I believe that life begins at conception and I cannot disregard the sanctity o f human life. With that belief comes my conviction that one human life cannot be harmed at the expense of another human life, even though there are potential medica l benefits. I personally have a problem with using excess embryos from in vitro fertilization for research despite the likelihood that those embryos will be thrown away. T he se embryos have the potential of forming into a human. Because they have the potent ial of being a human, I do not support proactively ending life. I do not believe stem cell research should stop altogether; r ather the focus should be on alternative sour ces to ESCs I am fully aware of the advantages ESCs have to offer for advancing tre atment. Kris Boesen was able to regain the ability to use his arms and his hands through the administration of

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 25 ESCs into h is spinal cord (Aldrich, 2016). I have an uncle who has Parkinson's disease and I recognize how he could be positively impacted. Howev er, just because there are potential medical benefits this does not validate the destruction of embryos. Continued research on alternative pluripotent sources may cause scientists to discover new potential that has not yet been seen. As reprogramming technology improves to complete reprogramming, iPSCs may become a viable treatment. My further support for iPS Cs is the hope that an allogenic transplant will no longer be necessary, and therefore deaths caused by GVHD could be reduced. I realize that even though I oppose ESC research, it is not going to be terminated. Therefore, I believe organizations like the NIH and NAS are vital in ensuring ethical research and the public's opinion is crucial in keeping guidelines updated Even with the strict guidelines, there remains a potential for ethical abuse so I am a proponent of scientific ethics committees in private resea r ch to discourage ethical abuse. I would also like to see more use of scientific ethics com mittees in government research. B ecause r esearch with adult stem cells and iPSCs are less controversial, policies that are established need not chan ge with each new president. Thus, the ethical issues which typically involve the more controversial ESCs could be avoided. Further since states are already setting stem cell polic ies, it may be beneficial to allow states to lead the way. This means less f ederal government in volvement and l ess government bureaucracy could pave the way for quicker progress in research I do not agree with the CIRM, but it has allowed continual research despite presidential changes. Being a biology major and a hopeful health care provider, my goal is to help all people, especially those that are helpless. All life is sacred and deserves to be protected. I believe stem

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 26 cell research is highly important; r eligious, ethical, and political views do not have to inhibit scientific progress. However, b y focusing on adult stem cells and iPSCs, w e can all come together to continue to better medicine in the United States.

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 27 REFERENCES Aldrich, M. (2016). Experimental stem cell therapy helps paral yzed man regain use of arms and hands. Retrieved from news.usc.edu Ashcroft, J.R. (2005). 2006 ballot measure constitutio nal amendment 2. Retrieved from www.sos.mo.gov Bali, C., Ozmete, O., Ozyilkan, N.B., Akin, S. & Aribogan, A. (2016). A short view of chronic graft vs hos t disease. Journal of Clinical Anesthesia, 30, 4 5. Bartlett, R.G. (2005). All bill information (except text) for H.R. 31 44 Respect for life pluripotent stem cell act of 2005. Retrieved from http s://www.congress.gov/bill/109th congress/house bill/3144/al l info Bean, M. (2008). Ballot Proposal 08 02. Retrieved from www.house.mi.gov Bottum, J. & Anderson, R. (2008). Stem cells: a political history. First Things: A Monthly Journal of Religion and Public Life, 187, 15. Boyer, L.A., Lee, T.I., Cole, M.F., Johnstone, S.E., Levine, S.S. Zucker, J.P., Guenther, M.G., Kumar, R.M., Murray, H.L., Jenner, R.G., et al. (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell, 122, 947 956. Bush, G.W. (2010). Decision points. New York: Crown Publishers. California Government. (2004). Proposition 71. Retrieved from www.cirm.ca.gov California Government. (2004). Proposition 71. Retrieved from www.lao.ca.gov California Institute for Regenerative Medicine (2016). Brende n Whittaker, Evangelina Padilla Vaccaro, and Jake Javier [Photograph]. Retrieved from https:// www.cirm.ca.gov/our progress/stories hope cirm stem cell four California Institute for Regenerative Medicine (2016). Stories of hope: The CIRM stem cell four. Retr ieved from https://www.cirm.ca.gov/our progress/stories hope cirm stem cell four Coburn, T. (2005). All bill information (except text) for S. 155 7 Respect for life pluripotent stem cell act of 2005. Retrieved from http s://www.congress.gov/bill/109th cong ress/senate bill/1557/all info DeGette, D. (2013). H.R. 2433 Stem cell research advancem ent act of 2013. Retrieved from www.congress.gov Gallup. (2016). Medical research using stem cells obtained from humans [Infographic]. Retrieved from http://www.gallu p.com/poll/21676/stem cell research.aspx

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 28 Genetic Science Learning Center. (2014). Stem cell quick reference [Images]. Retrieved from learn.genetics.utah.edu Glick, J.L. (2011). Arguments in support of embryonic stem cell funding. If the practice of in vitro is not unlawful, then why should hESC research be? Genetic Engineering & Biotechnology News, 31, 1. Hanegraaff, H. (2008). The Complete Bible Answer Book Collector's Edition. Nashville: Thomas Nelson. Hanna, J.H., Saha, K., & Jaenishch, R. (2010). Pluripotency and cellular reprogramming: Facts, hypotheses, unresolved issues. Cell, 143, 508 525. Hosseini, E., Ghasemzadeh, M., Kamalizad, M., & Schwarer, A. P. (2016). Ex vivo expansion of CD3 depleted cord blood_MNCs in the presence o f bone ma rrow stromal cells; an appropriate strategy to provide functional NK cells applicable for cellular therapy. Stem Cell Research, 19, 148 155. Iger, G. (2016). Kris Boesen works to strengthen his upper body [Photograph]. Retrieved from news.usc.edu Jaenisch, R. & Young, R. (2008). Stem cells, the molecular circui try of pluripotency and nuclear reprogramming. Cell, 132, 567 582. Jansen, J. (2005). The first successful allogeneic bone marrow transplant: George Math ÂŽ Transfusion Medicine Reviews, 19, 246 248. Kamao, H., Mandai, M., Okamoto, S., Sakai, N., Suga, A., Sugita, S., Kiryu, J., & Takahashi, M. (2014). Characterization of human induced pluripotent st em cell derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Reports, 2, 205 218. Khanlarkhani, N., Baazm, M., Mohammadzadeh, F., Najafi, A., Mehdinejadiani, S., & Sobhani, A. (2016). Multipotent stem cell and reproduction. Journal of Stem Cells, 11, 219 229. King, P.T. (2005). H.R.2541 Joe testaverde adult stem cell resea rch act of 2005. Retrieved from https://www.congress.gov/bill/109th congress/house bill/2541/text Kington, R.S. (2009). National institutes of health guidelines on human stem cell res earch. Retrieved from https://stemcells.nih.gov Ku mar, R., Sharma, A., Pattnaik, A.K., & Varadwaj, P.K. (2010 ). Stem cells: An overview with respect to cardiovascular and renal disease. Journal of Natural Science, Biology and Medicine, 1, 43 52.

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 29 Laino, G., Graziano, A., d'Aquino, R., Pirozzi, G., Lanza V., Valiante, S., et al. (2006). An approachable human adult stem cell source for hard tissue engineering. Journal of Cellular Physiology, 206, 693 701. Lee, M., Moon, S.H., Jeong, H., Yi, J., Lee, T., Shim, S.H ., et al. (2013). Inhibition of pluripotent stem cell derived teratoma formation by small molecules. PNAS, 110, 3281 3290. Martello, G. & Smith, A. (2014). The nature of embryonic stem cells. Annual Review of Cell and Developmental Biology, 30, 647 675. McCormack, K. (2016). Stem cell transplant offers Jake a glimpse of hope. Retrieved from blog.cirm.ca.gov Medvedev, S.P., Shevchenko, A.I., & Zakian, S.M. (2010). Induced pluripotent stem cells: Problems and advantages when applying them in regenerative medicine. Acta Naturae, 2, 18 28. Millender McDonald, J. (2005). H.R. 162 Stem cell replenishm ent act of 2005. Retrieved from https://www.congress.gov/bill/109th congress/house bill/162 Mimeault, M. & Batra, S.K. (2008). Recent proress on tissue R esident adult stem cell biology and therapeutic implications. Stem Cell Reviews, 4, 27 49. National Archives and Records Administration. (2007). E xecutive order 13435: Expanding approved stem cell lines in ethically r esponsible ways. Retrieved from https://www.gpo.gov/fdsys/pkg/FR 2007 06 22/pdf/07 3112.pdf National Archives and Records Administration. (2009). Executive order 13505: Removing barriers to responsible scientific research involvin g h uman stem cells. Retrieved from https://www.gpo.gov/fdsys/pkg/FR 2009 03 11/pdf/E9 5441.pdf National Research Council, et al. (2005). Guidelines for human embryonic stem cell research. Washington D.C: National Academies Press. Nationa l Research Council, et al. (2010 ). Final report of the national acadmies' hu man embryonic research advisory committee and 2010 amendments to the national acade mies' g uidelines for human embryonic stem cell research. Washington D.C: National Academies Press. Niakan, K.K., Han, J., Pederson, R.A., Simon, C., & Reijo Pera, R.A. (201 2). Human pre implantation embryo development. Development, 139, 829 841. NIH. (2001). Human embryonic stem cell lines available under f ormer president bush. Retrieved from https://stemcells.nih.gov/research/registry/eligibilityCriteria.htm

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 30 NIH. (2015). Raynard S. Kington, MD. Retrieved from https://www.nih.gov/about nih/what we do/nih almanac/raynard s kington md NIH. (2015). Advisory committee to the director. Retrieved from https://acd.od.nih.gov/charter.html NIH. (2016). NIH human embryonic stem c ell registry. Retrieved from https://grants.nih.gov/stem_cells/registry/current.htm Office for Human Research Protections. (2 009). 45 CFR 46. Retrieved from https://www.hhs.gov/ohrp/regulations and policy/regulations/45 cfr 46/ Office of the Press Secretary. (1993). Remarks by the president in bill signing of the national institutes of health revitalization act of 1993. Paul, R. (2005). H.R.3444 Cures can be fo und act of 2005. Retrieved from https://www.congress.gov/bill/109th congress/house bill/3444 Santorum, R. (2006). S.2754 Alternative pluripotent stem cell therapies enhancement act. Retrieved from https://www.congress.gov/bill/109th congress/senate b ill/2754 Scientific Ethics Committee. (2017). For review of unreg ulated research. Retrieved from http://www.ucdenver.edu/research/ORC/RI/Pages/SEC.aspx Singh, R., Shen, W., Kuai, D., Martin, J.M., Guo, X., Smith, M. A., Perez, E.T., Philips, M.J., Simonett, J.M., Wallace, K.A., et al. (2013). iPS cell mod eling of best disease: Insights into the pathophysiology of an inherited macular degeneration. Human Molecular Genetics, 22, 593 607. Specter, A. (2005). S. 471 (109 th ): Stem cell research enhancem ent act of 2005. Retrieved from https://www.govtrack.us/congress/bills/109/s471 Vitter, D. (2015). S. 43 Ethical stem cell research tax credit act of 2015. Retrieved from www.congress.gov Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., et al. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES cell like state. Nature, 448, 318 324. Yu, J. & Thomson, J.A. (2008). Pluripotent stem cell line. Genes & Development, 22, 1987 1997. Zhang, X., Stojkovic, P., Przyborski, S., Cooke, M., Armstron g, L., Lak, M., & Stojkovic, M. (2006). Derivation of human embryonic stem cells from devel oping and arrested embryos. Stem Cells, 24, 2669 2676.

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 31 Appendix

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ETHICAL DILEMMA OF EMBRYONIC STEM CELL RESEARCH 32