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IQP-43-DSA-3698
STEM CELLS AND SOCIETY
An Interactive Qualifying Project Report
Submitted to the Faculty of
WORCESTER POLYTECHNIC INSTITUTE
In partial fulfillment of the requirements for the
Degree of Bachelor of Science
By:
____________________
Philip Lauinger
January 19, 2010
APPROVED:
_________________________
Prof. David S. Adams, Ph.D.
Project Advisor
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ABSTRACT
The purpose of this project is to investigate and assimilate information on a variety of
topics related to stem cells, and determine the impact of this technology on society. In this report,
the information is divided into four chapters to gradually lead the reader deeper into the topic.
The first chapter is an introduction to stem cells and their sources. The second chapter is an
explanation of the current and potential applications for stem cells in disease treatment. The third
chapter delves into the ethical issues surrounding the stem cell debate. The fourth chapter
examines the political policies involving stem cell research throughout the world, and the
significance of the technology on society. Through comprehensive research it was concluded that
stem cell research has the potential to be extremely advantageous to society. With current
legislative practices in the United States under President Obama, stem cell research should have
a strong impact on our culture.
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TABLE OF CONTENTS
Signature Page …………………………………………………………………….. 1
Abstract ……………………………………………………………………………. 2
Table of Contents ………………………………………………………………….. 3
Project Objectives ……………………………………...……………………………4
Chapter-1: Stem Cell Introduction ………..…...………………………………… 5
Chapter-2: Stem Cell Applications ..……………………….…………………….. 16
Chapter-3: Stem Cell Ethics ……………………………………….……………… 30
Chapter-4: Stem Cell Legalities ………………………..…………………………. 38
Project Conclusions …………………………………………….….……………… 50
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PROJECT OBJECTIVES
The objective of this IQP project was to investigate the highly controversial topic of stem
cells, and express opinions on the effect of this technology on society. Chapter-1 serves to
introduce the reader to the topic of stem cells and describe their types, how they are classified,
and how we currently isolate them. The purpose of Chapter-2 is to document the treatment of
different diseases with stem cells in both animal model systems and in human clincial trials.
Chapter 3’s purpose is to study the ethical debates raging within the global community on this
topic, and relate the five world religions’ perspectives on the issue. Chapter 4 is dedicated to
investigating the history of U.S. and International political policies and legislation governing
stem cell research. Lastly, the author brings the report to a conclusion on the topic of the use of
stem cells and which legislation best represents the overall views of the author on the topic.
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Chapter 1: Stem Cell Introduction Types and Sources
What are Stem Cells?
Stem cells have the remarkable potential to develop into many different cell types in the body
during early life and growth, and in the adult in many tissues they serve as a sort of internal repair
system, dividing essentially without limit to replenish other cells as long as the person or animal is still
alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become
another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain
cell.
Stem cells are distinguished from other cell types by two important characteristics. First, they
are unspecialized cells capable of renewing themselves through cell division, sometimes after long
periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced
to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and
bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other
organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.
Stem cells can be grouped into two main categories. These are Embryonic Stem Cells (ESCs) and
Adult Stem Cells (ASCs). Embryonic stem cells are present only during early development, whereas ASCs
exist in fully grown organisms. Stem cells can be further categorized based upon their relative potential
to differentiate. The first are totipotent cells. These have the ability to divide and produce all of the
cells in an organism, including all cells of an adult organism and extra-embryonic tissue such as the
placenta during pregnancy. The human zygote is an example of a totipotent cell (Regenerative
Medicine, 2009). Totipotent cells can specialize into pluripotent cells. Pluripotent cells can differentiate
into all cells of an adult organism, but cannot form extra-embryonic tissue. Embryonic stem cells are
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pluripotent. Pluripotent cells can differentiate into any of the three germ layers: endoderm, mesoderm,
and ectoderm, which form all cells in the body. From these cells, further specialization can occur to
form multipotent cells. These cells usually differentiate into groups of related cell types. For example,
multipotent hematopoietic stem cells form all the cellular components of blood, but do not usually form
other unrelated cells. Mesenchymal stem cells are also multipotent. Multipotent cells have the
potential to differentiate into unipotent cells that form only one type of cell with a specific function.
The most common unipotent cells are skin cells.
Embryonic Stem Cells
Embryonic Stem Cells (ESCs) are pluripotent cells derived from the inner cell mass of a 5 day old
blastocyst. The blastocyst (Figure-1, upper center) is a hollow ball of cells about the size of the period at
the end of this sentence, made up of the blastocoel cavity, the trophoblast cells lining the embryo, and
the inner cell mass (Figure-1, blue cells). The inner cell mass cells are undifferentiated, and can give rise
to any cell in the body via the three germ layers (Figure-1, lower diagram).
ESCs used in research are usually derived from in vitro fertilized (IVF) embryos. Once a family is
done using them, the excess embryos are usually discarded, so discarded IVF embryos are the primary
source of ESCs for research. The fertilized embryos are grown in a test tube to about day-5 to form the
blastocyst. The inner cell mass cells are then obtained using a micro-syringe, and can be cultured in vitro
for years making an embryonic stem cell line. Mouse ESCs injected into another mouse blastocyst have
been shown to differentiate into all types of cells of the adult mouse. Throughout their life, ESCs
maintain the ability to give rise to all body cell types. Scientists are currently devising protocols for
differentiating ESCs into various tissues in vitro.
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Figure 1: Characteristics of Embryonic Stem Cells. ESCs are derived from the inner cell mass (blue) of a blastocyst embryo (pink), and can self-renew (diagram middle), or can differentiate into all three types of germ layers (diagram lower). (Winslow, 2006).
Mammalian ESCs were first derived in 1981, when Martin Evans and Matthew Kaufman isolated
pluripotent cell lines from cultures of mouse blastocysts. It took 18 years for the first human ESC
derivations to be reported (Thomson et al., 1998). ESCs are created from excess IVF embryos. Oocytes
and sperm are placed together in a culture dish to allow fertilization to occur outside the body. The cells
divide for 5 days to form the blastocyst, from which the inner cell mass ESCs are isolated. The ESCs
divide to cover a petri dish pre-coated with a “feeder cell” layer. This layer of cells provides the ESCs
with essential growth factors and also provides a surface to stick to. The feeder cells were originally
made up of mouse fibroblasts in bovine serum (Kirchstein and Skirboll, 2001), but due to scientific and
ethical concerns of co-culturing human cells with animal cells more recently a “feeder-free” human ESC
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culture system has been developed to minimize the possibility of animal pathogen introduction into the
cell culture. This process involves placing the ESCs onto easily sterilizable extracellular matrix (ECM)-
coated plates (Klimanskayza et al., 2006).
Even though ESC derivation and culture conditions have been established, the efficiency of
deriving human ESCs is still very low compared to mouse. The ideal growth medium would be easy to
use, inexpensive, and would contain growth factors to minimize the rate of genetic and epigenetic
changes in culture (Regenerative Medicine, 2006).
Adult Hematopoietic Stem Cells
Adult stem cells are somewhat rare in the human body compared to the differentiated cell
population. However, Hematopoietic Stem Cells (HSCs) are the most common type of adult stem cells.
HSCs are found in the bone marrow (Figure-2, left side) and spleen, and are normally used by the body
in the formation of new blood cells, both red (diagram center) and white (diagram upper center and
upper right). Only an estimated 1 in 15,000 cells in bone marrow is a HSC (Weissman, 2000). These cells
are defined by their ability to self-renew and differentiate into all types of blood cells in the body. Red
cells are used in the distribution of food, oxygen, and waste throughout the body. White blood cells
come in various forms, and are all used for immunity from pathogens.
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Figure 2: Diagram of Hematopoietic and Stromal Stem Cell Differentiation. Bone marrow (left side) is the most common source of HSCs (pink cell diagram center). HSCs can form all the cellular components of blood, including red blood cells (red cells diagram center), and white blood cells (diagram upper center and upper right). (Regenerative Medicine, 2006).
The majority of HSCs are found in bone marrow, and these cells have been used for over 30
years in bone marrow transplants (discussed in Chapter-2). HSCs can also be obtained from umbilical
cord blood, or from the peripheral blood stimulated with cytokines to mobilize the HSCs from the
marrow. Due to the relative ease of isolation, the cytokine mobilization procedure is generally replacing
bone marrow as the preferred source for HSCs.
Over the past 40 years, scientists have attempted to identify surface protein markers that
distinguish HSCs from other cell types. Scientists currently believe that HSCs express c-kit, CD34, and H-
2K proteins on their surface. Two types of HSC have been defined from these isolations: long-term and
short-term HSCs. Long-term HSCs propagate the entire lifetime of an animal, and have high levels of
telomerase activity (an enzyme found in long lived cells that helps them maintain long telomere ends of
their chromosomes). Short-term HSCs may only propagate for a few months, and can differentiate into
lymphoid and myeloid precursors for the two major lineages of blood cells. Though HSCs have been
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shown to propagate in vivo, scientists have not been able to easily induce their growth in vitro
(Regenerative Medicine, 2006), although some success has recently been achieved for the in vitro
propagation of human umbilical cord blood HSCs (Viacell, 2008).
Adult Neuronal Stem Cells
Adult Neuronal Stem Cells (NSCs) are cells that can generate neural tissue and possibly repair
the nervous system. These cell types were discovered while studying the development of blood cells.
Stem-like cells were originally isolated from the embryonic central and peripheral nervous systems, but
recently stem-like cells have also been isolated from the adult brain. NSCs have been found in the
hippocampus and the sub-ventricular zone (SVZ) as well as the spinal cord (Figure-3). Because the
surface markers that define central nervous system stem cells are still being developed, they are
currently identified based upon their activities after separation (Temple, 2001).
Figure 3: Principal Regions of the Adult Nervous System Containing Neuronal Stem Cells (Temple, 2001).
The plasticity of NSCs has been examined by transplanting them directly into embryos and
examining which neural cells are produced. Spinal cord-derived NSCs can make neurons if injected into
the adult hippocampus (Shihabuddin et al., 2000), but there is no direct evidence that NSCs can make
neurons similar to those derived from ESCs.
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Adult Cardiac Stem cells
Until recently, the adult heart has been thought of as an organ without regenerative capacity.
However, in the past few years cycling ventricular myocytes have been documented in adult mammalian
hearts (Quaini et al., 2002). During cardiac transplants between different-sex humans, some cardiac
chimerism was displayed in which new male cells occurred in the transplanted female heart presumes
the existence of stem-like cells able to differentiate into the three main cardiac cell types. Primitive cells
that expressed antigens c-kit, Sca-1, and MDR1, frequently associated with stem cells, were identified in
both the recipient and control hearts, thus these cells may be true cardiac stem cells, but the exact
lineage of these cells is still unknown (Beltrami et al., 2003).
Researchers at New York Medical College in Valhalla identified pockets of stem cells in the
interstices between the muscle cells in rodent hearts. They also examined humans who had undergone
cardiac surgery and found very similar stem cells that had been attempting to repair the heart damage
(Urbanek et al., 2003). The presence of these cells strongly suggests that the heart retains a stockpile of
stem cells to repair damaged tissue (Touchette, 2004). Figure-4 shows these cardiac stem cells located
between human heart cells.
Figure 4: Photograph of Cardiac Stem Cells. The cardiac stem cells are stained blue, while the cardiac muscle cells are stained red. (Urbanek et al., 2003)
Adding to these past discoveries, Kenneth Chien, at the Keystone Symposium on Molecular
Pathways in Cardiac Development and Disease, in Breckenridge, CO, took the findings a significant step
forward. His team found an early multipotent embryonic cardiovascular cell expressing protein Isl1 and
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that can give rise to the three cardiac lineages: cardiac myocytes, smooth muscle cells, and endothelial
cells, as shown in Figure-5 (Moretti et al., 2006).
Figure 5: Cellular Hierarchy of Cardiac Progenitors and Their Lineage Specification. Multipotent cardiovascular progenitor cells (green cells, diagram center) give rise to all 3 lineages of cardiac cells (diagram right). (Moretti et al., 2006)
Adult Epithelial Stem Cells
Adult epithelial stem cells can be found in several places. The epithelium proliferates at a very
rapid pace. There is evidence to support that epidermal cells are replaced by division from stem cells.
For example, in hair follicles scientists believe the epidermis is organized hierarchically, with stem cells
found near the “bulge” midway down the follicle (Figure-6). Because stem cells are slow-cycling and
highly proliferative during development they can be identified in vivo by labeling the cells with 3H-TdR .
This protocol is widely used to monitor rates of cell proliferation (Smits & Riemann, 1988). After 4-6
weeks, because of their slow-cycling nature, only the stem cells remain, which can then be identified
with immunohistology. The label-retaining cells are present both in the epidermis and hair follicle
(Cotsarelis et al., 1999).
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Figure 6: Cutaneous Epithelial Stem Cells. Epithelial stem cells in the bulge of the hair follicle give rise to at least 4 progenitor types. EPC: epidermal progenitor cell; EPU: epidermal proliferative unit; SC: Stem cell ; HPC: hair progenitor cell (Cotsarelis et al., 1999).
Another place epithelial stem cells are found is the lining of the colon. These cells give rise to
several cell types, and are controlled by interactions between mesenchymal cells and epithelial cells.
Mesenchymal Stem Cells
Adult mesenchymal stem cells (MSCs) are categorized as multipotent cells, and are found mainly
in the bone marrow of humans. Residing primarily in the stromal area of the bone marrow, these cells
have been shown to differentiate into many types of cells such as osteoblasts, chondrocytes, and
adipocytes (Figure-7). MSCs have also been isolated from a wide range of tissues, including peripheral
blood, adipose tissue, trabecular bone, and even amniotic fluid. Isolation of MSCs is currently done by
sorting bone marrow populations by flow cytometry to various antibodies. MSCs have been shown to
be very versatile, even with the potential to repair tissues outside the mesenchymal lineage. Due to
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their multilineage potential, and their relative ease of isolation, MSCs are becoming increasingly popular
for cell therapy experiments, but further research will be necessary to more fully define their potential
(Jackson et al., 2007).
Figure 7: Mesenchymal Stem Cell Lineage (HemoGenix, 2009)
Chapter-1 Bibliography
Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, et al. (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114: 763-776. Cotsarelis G, Kaur P, Dhouailly D, Hengge U, Bickenbach J (1999) Epithelial stem cells in the skin: definition, markers, localization and functions. Experimental Dermatology 8: 80–88. Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154–156. HemoGenix (2009) Mesenchymal Stem Cell System. http://www.hemogenix.com/the_mesenchymal_stem_cell_system/
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Jackson L, Jones DR, Scotting P, Sottile V (2007) Adult mesenchymal stem cells: Differentiation potential and therapeutic applications. Journal of Postgraduate Medicine 53: 121-127.
Kirschstein R, Skirboll LR (2001) Stem cells: Scientific progress and future research directions. National Institutes of Health, Department of Health and Human Services. http://stemcells.nih.gov/info/basics/ Klimanskayza I, Chung Y, Becker S, Lu S, Lanza R (2006) Human embryonic stem cell lines derived from single blastomeres. Nature 444: 481-485. Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, et al. (2006) Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127: 1151-1165. Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, and Anversa P (2002) Chimerism of the transplanted heart. N. Engl. J. Med. 346: 5–15. Regenerative Medicine (2006) Department of Health and Human Services. http://stemcells.nih.gov/info/2006report/ Regenerative Medicine (2009) Vol. 4, No. 4s, Pages S1-S88. Shihabuddin LS, Horner PJ, Ray J & Gage FH (2000) Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J. Neurosci. 20: 8727–8735. Smits JD, Riemann B (1988) Calculation of cell production from [H] thymidine incorporation with freshwater bacteria. Appl. Environ. Microbiol. 54: 2213-2219. Temple S (2001) The development of neural stem cells. Nature 414: 112-117. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147. Touchette N (2004) Stem cells found in the heart. http://www.genomenewsnetwork.org/articles/10_03/cardiac.shtml Urbanek K, et al. (2003) Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc. Natl. Acad. Sci. U.S.A. 100: 10440-10445. Viacell (2008) www.viacellinc.com Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100: 157–168.
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Chapter 2: Stem Cell Applications Diseases and Treatments
Stem Cell Application Introduction
The idea of growing personalized organs from one’s own cells, or healing spinal cord injuries,
was once a pipe dream. Now because of advances in science today, stem cells are being used in
applications ranging from treating diabetes, leukemia, and Parkinson’s disease, to repairing damaged
heart tissue and bone marrow (Flanagan, 2007). In addition, there is much confusion in the press about
what has in fact been done with stem cells, versus what remains for future applications. The purpose of
this chapter is to accurately summarize what has been done with stem cells for certain diseases, while
especially distinguishing fact from hype.
There is a strong debate raging in bioethics today about using embryonic stem cells (ESCs) to
cure diseases, yet not one human patient has been cured to this day using these cells. Adult stem cells
(ASCs) are readily available from many sources, as discussed in the previous chapter, and provide
concrete results with patients today. While the successes of adult stem cell treatments are becoming
clear, treatments with embryonic stem cells have either not received approval for testing, or have not
shown any clinical successes (Sipione et al., 2004). Currently, upwards of 70 diseases and disabilities are
treatable using non-embryonic stem cells (Earll, 2005). For example, in 2001, 11 out of 15 Type I
diabetes patients were successfully removed “completely off insulin” after receiving transplants of adult
pancreatic cells (Cell grafts, 2001). In 2002, a California man with Parkinson’s disease experienced more
than an 80 percent reduction in his symptoms after receiving an injection of his own neuronal stem cells
(Stem cell transplant, 2002). In 2003, patients with heart failure saw significant improvements after
receiving infusions of their own bone marrow stem cells, and four out of five seriously sick Brazilian
heart-failure patients no longer needed transplants after being treated with their own bone marrow
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stem cells (Perin et al., 2003). While these human cases have been documented in clinical trials, many
other diseases are in the process of being cured through animal studies and non-human trials (Hughes,
2005).
Treating Diabetes with Stem Cells
Diabetes is a terrible disease that reaches worldwide, affecting millions of people. There are two
major forms of diabetes: type I and II. Type I diabetes is an autoimmune disorder that destroys the β-
cells of the pancreas. These cells produce insulin, a hormone that modulates blood glucose
concentration in the blood. Type I diabetes usually begins in childhood, and eventually results in a
complete dependence on exogenous insulin treatments (Assasy et al., 2005). Type II diabetes, the more
common of the two, is characterized by tissue resistance to insulin; eventually the cells cannot produce
enough insulin to overcome the resistance (Goldthwaite, 2006). Type II diabetes is a metabolic disorder
that, unlike type I, is largely preventable. An active lifestyle and a healthy diet are often enough to
prevent the onset of type II diabetes.
Diabetes poses a significant health issue for the world. According to the International Diabetes
Federation, the disease affects nearly 250 million people, 7% of the world’s population. This number is
expected to rise to 380 million by 2025 due to aging populations, obesity, and sedentary lifestyles
(Table- 1) (International Diabetes Federation, 2007). It is currently the sixth leading cause of death in
the U.S., and is associated with many health complication including heart disease, stroke, kidney
disease, blindness, and amputations. To put it into a bigger perspective, the American Diabetes
Association estimates that 1 in 10 health care dollars currently spent is used for diabetes (American
Diabetes Association, 2008).
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Table 1: Summary of the Worldwide Diabetes Population. Estimated numbers (in thousands) of people with diabetes by world region for 2000 and 2030, and summary of population changes (Wild et al., 2004).
Because there is presently no cure for diabetes, there is extreme interest in exploring stem cells
as a possible therapeutic option. Theoretically, stem cells could be used as a treatment by growing a
population of β-cell precursor cells from donor tissue and then inducing differentiation in vitro into
insulin-producing cells for transplant into the patient’s liver (Lechner & Habener, 2003). Thus, much
recent research has focused on the possibility of harvesting adult pancreatic stem cells. The key step for
using stem cells to treat diabetes is to identify the precursor cells that give rise to β-cells. Animal studies
are the first step to this identification. Several recent studies in rodents have shown that the pancreas
contains rare endocrine progenitor cells that can differentiate into β-cells (Soria et al., 2005). Raewyn
Seaberg and his associates identified multipotent precursor cells in the adult mouse pancreas that could
proliferate in vitro and could differentiate into pancreatic β-cells that demonstrated glucose-dependent
insulin release, so these cells could have therapeutic applications for diabetes (Seaberg et al., 2004).
However, in contrast to this finding, Dor used genetic lineage tracing in mice to conclude that new β-
cells arise from pre-existing β-cells rather than from pluripotent stem cells in adult mice (Dor et al.,
2004). Thus despite much research, it is still not known conclusively whether new β-cells arise from
existing β-cells or from pancreatic stem cells. But in either case, so long as culture conditions can be
established for replicating the β-cells regardless of their origin, such cells could be used for therapy.
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With respect to using embryonic stem cells to treat diabetes, some success has been reported
treating mouse diabetic models with pancreatic-like cells differentiated from ES cells (Soria et al., 2002).
And in humans, ES cells have been induced to secrete insulin in a glucose-dependent manner (Assady et
al., 2001; Lumelsky et al., 2001; D’Amour, 2006), but these cells have not yet been used to treat human
patients.
Since an adult pancreatic stem cell population has not convincingly been identified, and since
the β-like cells derived from ES cells have not been approved for human use, there are currently no stem
cell diabetes clinical trials underway. While stem cells must currently be considered a frontier for
diabetes therapy, hopefully one day they will become its foundation.
Treating Cardiovascular Disease with Stem Cells
Cardiovascular disease (CVD) includes hypertension, coronary heart disease (CHD), stroke, and
congestive heart failure (CHF), and has ranked as the number one cause of death in the United States
nearly every year since 1900 (American Heart Association, 2005). Heart failure occurs when cardiac
tissue is deprived of oxygen. When this deprivation is severe enough to cause the loss of many cardiac
muscle cells, it often begins a slippery slope of problems including the formation of non-contracting
tissue and the thinning of the ventricular wall to eventually cause heart failure and death (Rosenstrauch
et al., 2005). The aging U.S. population and other cardiovascular risk factors suggest that CVD is going to
continue be an important health concern in the near future, thus there is clearly a need for therapies to
regenerate or repair damaged cardiac tissue.
There are currently many approaches to combat heart disease, but none have been able to
completely solve the associated problems. Beta blockers, diuretics, and angiotensin-converting enzyme
inhibitors, as well as implanting assistive devices like defibrillators and pacemakers, do not repair the
damaged tissue and only lessen the detrimental effects of lost cardiac function. In addition to these
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partial therapies, heart transplants are really the only way to replace damaged cardiac tissue but pose
problems such as organ rejection. Thus, researchers have begun exploring other options, including
using stem cells for cardiac repair (Goldthwaite, 2006).
Many different types of stem cells have been tested, including embryonic stem cells, skeletal
myoblasts (SM), mesenchymal (bone marrow stromal) stem cells, and resident cardiac stem cells, and
some have shown impressive results. Studies in both rats and humans have shown that skeletal
myoblasts can repopulate scar tissue and improve left ventricular function after transplantation (Dowell
et al., 2003), but transplanted SM cells do not contract in complete sync with the rest of the cardiac
tissue.
With respect to stem cells, an experiment in swine using transplanted mesenchymal stem cells
indicated that over 60% of the damaged area was repaired (Shake et al., 2002). Due to the success of
treating animal heart attack models with stem cells, a wide range of clinical studies have been
performed over the past few years. Reports have shown that patients with heart attacks have been
successfully treated with adult cardiac stem cells (Britten et al., 2003; Randerson, 2003; Siminiak et al.,
2004), mesenchymal stem cells (Schächinger et al., 2006), and bone marrow stem cells (Lunde et al.,
2006; Schächinger et al., 2006). With respect to embryonic stem cells, studies have shown that human
ES cells can differentiate into cardiac lineages (Kehat et al., 2001), but ES cells have not yet been tested
in clinical trials for heart attack patients. Hopefully in the near future, more clinical trials can be
performed to get a better understanding of the potential for using stem cells to treat this terrible
disease.
Treating Parkinson’s Disease with Stem Cells
Parkinson’s disease is the second most common form of neurological disease. It is caused by the
progressive loss of the dopaminergic (DA) neurons (Figure-8) in the brain that release dopamine
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involved in neuronal communication, especially as related to muscular function. When these
dopaminergic cells are destroyed, many symptoms begin to develop including tremor, rigidity,
hypokinesia (decreased muscle activity), and difficulties with balance and walking. Currently,
Parkinson’s disease is treated with medications containing dopamine replacements, but these
medications only temporarily treat the symptoms, and do not slow or prevent the natural progression of
the disease (Garfinkel, 2005). The average age of onset for all forms of Parkinsonian syndromes is about
60, and as the population ages the cases in the U.S. are expected to double from 350,000 to 600,000 by
2030 (Dorsey et al., 2007).
Figure 8: Diagram of Parkinson’s Disease. The figure shows the differences in brain signal transmission for a healthy brain (left panel) versus a a brain affected by Parkinson's Disease (PD) (right panel). Note that in PD, the lack of dopamine secretion (dark yellow) removes the dampening effect on the reticular formation (light blue) from the basal ganglia (light yellow). (Holistic Online, 2007)
To treat PD with stem cells, the problem is to identify and develop stem cell lines that
differentiate into precursors for DA neurons. Some success has been achieved in animals and humans
grafting embryonic DA neurons from aborted fetal tissue (Madrazo et al., 1988; Lindvall et al., 1989;
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Quinn, 1990; Freed et al., 2001, Mendez et al., 2002), but such studies have been discontinued in the
U.S. and many countries due to strong ethical concerns. With respect to adult stem cell treatments for
PD, human PD patients have successfully been treated with adult olfactory mucosal stem cells
(Levesque, 2005), but few other studies have been successful.
With respect to treating PD with embryonic stem cells, ES cell suspensions grafted into rodent
striatum (the inner part of the cerebrum in the brain), differentiated into adult DA neuronal cells after
transplantation in vivo (Björklund et al., 2002). Redmond and colleagues have extended the ESC
approach into primates, showing that the microenvironment of the diseased brain can strongly
influence the phenotype of the transplanted cells (Capone et al., 2007). This group transplanted
undifferentiated human neural cells instead of predifferentiated dopamine precursors into Parkinsonian
primates and the apes showed remarkable improvements in symptoms (Redmond et al., 2007).
Allowing the brain to determine the fate of the donor cells and their corresponding reparative
properties may, in fact, be a key step in a successful stem cell therapy for Parkinson's patients (Sanberg,
2007).
No Parkinson’s patients have been treated yet with ES cell therapy, however human ES cells
have been shown to differentiate into dopamine-producing cells in vitro (Perrier et al., 2004). For clinical
trials, the potential for tumor formation and inappropriate stem cell migration must be minimized
before any Parkinson’s patients are enrolled in clinical trials (Sanberg, 2007). Significant further
preclinical testing on primates must occur to demonstrate safety and efficacy before human clinical
trials can begin.
Treating Leukemia with Stem Cells
Leukemia is a group of bone marrow diseases which involve an uncontrolled increase in
immature nonfunctional white blood cells (leukocytes). Leukemia is often called blood cancer because
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of the uncontrollable growth of these leukocytes. Every ten minutes, someone dies from leukemia or a
related blood cancer, which translates to almost 150 people per day. Current treatments include drug
and radiation therapy to destroy the rapidly dividing cells, immunotherapy to induce antibody formation
against the leukemic cells, gene therapy to correct a genetic defect causing the proliferation, and stem
cell transplantation to re-grow healthy leukocytes. Several new drugs have been introduced in the past
decade that have greatly improved remission rates for many people, but some of these drugs destroy
healthy cells and do not rebuild lost tissue (Leukemia & Lymphoma Society, 2009).
Hematopoietic stem cells (HSCs) have been used clinically in humans since 1959 to treat
hematopoietic cancers (leukemias and lymphomas), to recover from the use of high-dose
chemotherapy, or to treat other diseases such as aplastic anemia, thalassemia, sickle cell anemia, or
autoimmune diseases (Horowitz, 1999; Santos, 2000). Thus, HSCs are the most characterized type of all
stem cells. Currently, about 40,000 transplants are performed annually world-wide. HSC
transplantation is a very important therapy leukemia because HSCs are used to restore the function of
the bone marrow that has been damaged either from the cancer or the previous drug treatments. Most
types of stem cell transplants for treating blood cancer are autologous, which means that the patient
has his or her own cells harvested and then infused back into the body following radiation treatment or
chemotherapy (Figure-9). HSCs are most often harvested from the patient’s bone marrow.
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Figure 9: Diagram of Autologous Bone Marrow Transplantation of Hematopoietic Stem Cells. Bone marrow containing hematopoietic stem cells is harvested from the patient’s hip bone, then given back to the same patient after the leukemia cells in the patient's bone marrow have been destroyed with chemotherapy or irradiation (Lavelle, 2004).
Although bone marrow is the most frequent source for obtaining HSCs, other alternatives have
been discovered as viable options, including the use of umbilical cord blood or HSCs mobilized into the
peripheral blood using hormones. In 2004, a study published in the New England Journal of Medicine
confirmed that stem cells derived from the umbilical cords of babies are a useful and effective
transplant source for leukemia patients without matched relatives. An analysis and comparison of
treatment results in over 500 patients was conducted, and the results showed a significantly improved
survival rate over those who did not receive cord blood (University Hospitals of Cleveland, 2004).
Ongoing research into leukemic cells and their origins has brought on new knowledge and
theories. We now know that bone marrow is the primary site of leukemic relapse. One very important
component in the marrow is the mesenchyme containing mesenchymal stem cells (MSC). These cells
have been demonstrated to protect and shield leukemiccells from apoptosis (Gibson, 2002), so some
research is focusing on how to induce MSCs to kill leukemic cells. In a recent study, researchers found
25
that blocking a specific signaling pathway, PI3K-Akt-Bad, in MSCs may remove the shielding effects, and
help them kill leukemic cells (Wei et al., 2009).
These are only a few of the advances in treating leukemia recent years, but many other new
treatments are under study in clinical trials to help a growing number of patients achieve remission.
Chapter-2 Conclusion
Although many problems have been solved through stem cell research with regards to the
treatment of diabetes, damaged cardiac muscle, Parkinson’s disease, and Leukemia, there still remain
many unanswered questions. Most of the human applications of stem cells involve the use of adult
stem cells of various types since these cells have fewer ethical concerns than ESCs. Only time and more
research will tell how well the treatments will work and which stem cells, if any, are best for combating
specific diseases. There is a vast world of knowledge of which we have just begun to graze the surface in
the applications of stem cells. Hopefully, with the current favorable political atmosphere and the recent
removal of tight regulations for federal support of ESC research, researchers now have all the tools at
their disposal to explore new applications.
Chapter-2 Bibliography American Diabetes Association (2008) Economic costs of diabetes in the U.S. in 2007. Diabetes Care 31: 596-615. American Heart Association (2005) Heart disease and stroke statistics–2005. Dallas: American Heart Association. Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki K, and Tzukerman M (2005) Insulin production by human embryonic stem cells. http://diabetes.diabetesjournals.org/cgi/content/full/50/8/1691
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Björklund LM, Sanchez-Pernuate R, Chung S, Andersson T, Chen IYC, McNaught KSP, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation into a Parkinsonian rat model. Proc Natl Acad Sci 99: 2344-2349. Britten MB et al (2003) Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction. Circulation 108: 2212-2218. Capone C, Frigerio S, Fumagalli S, Gelati M, Principato M-C, et al. (2007) Neurosphere-derived cells exert a neuroprotective action by changing the ischemic microenvironment. PLoS ONE 2: e373. “Cell grafts lend freedom to diabetics.” Medical Post, June 19, 2001. D’Amour K (2006) Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells. Nature Biotechnology 24, 1392-1401. Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429: 41-46. Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schifitto G, Siderowf A, Tanner CM (2007) Projected number of people with Parkinson’s disease in the most populous nations, 2005 through 2030. Neurology 68: 384-386. Dowell JD, Rubart M, Pasumarthi KB, Soonpaa MH, Field LJ (2003) Myocyte and myogenic stem cell transplantation in the heart. Cardiovasc Res. 58: 336–350. Earll CG (2005) Adult stem cells: it's not pie-in-the-sky. Focus on the Family. Flanagan, Nina (2007) Regenerative medicine enters realm of reality. Genetic Engineering News 27(7): 1. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, and Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N. Engl. J. Med. 344: 710-719. Garfinkel S (2005) Stem cells and Parkinson’s disease. International Society for Stem Cell Research. http://www.isscr.org/public/parkinsons.htm Gibson LF (2002) Survival of B-lineage leukemic cells: signals from the bone marrow microenvironment. Leuk Lymphoma 43: 19–27. Goldthwaite CA (2006) Are stem cells the next frontier for diabetes treatment? Regenerative Medicine. http://stemcells.nih.gov/info/scireport/PDFs/chapter7.pdf Goldthwaite CA (2006) Mending a broken heart: stem cells and cardiac repair. Regenerative Medicine. http://stemcells.nih.gov/info/scireport/PDFs/chapter6.pdf Holistic Online (2007) Understanding Parkinson’s disease. http://www.holisticonline.com/Remedies/parkinson/pd_brain.htm
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Horowitz MM (1999) Uses and Growth of Hematopoietic Cell Transplantation. In: Forman SJ, ed. Hematopoietic Cell Transplantation. Second ed. Malden, MA: Blackwell Science Inc. pg. 12-18. Hughes BR (2005) Real-world successes of adult stem cell treatments. Family Research Council. http://www.frc.org/index.cfm?i=IS04J01&f=WU04K19&t=e International Diabetes Federation (2007) Facts & figures: diabetes prevalence. http://www.idf.org/home/index.cfm?node=264 Kehat, I, Kenyagin-Karsenti, D, Druckmann, M, Segev, H, Amit, M, Gepstein, A, Livne, E, Binah, O, Itskovitz-Eldor, J, and Gepstein, L (2001) Human embryonic stem cells can differentiate into myocytes portraying cardiomyocytic structural and functional properties. Journal of Clinical Investigation 108: 407-414. Lavelle P (2004) Leukemia fact file. ABC Health & Wellbeing. http://www.abc.net.au/health/library/img/leukaemia_transplant.gif Lechner A, Habener JF (2003) Stem/progenitor cells derived from adult tissues: potential for the treatment of diabetes mellitus. Am J Physiol Endocrinol Metab 284: E259-E266. Leukemia & Lymphoma Society (2009) Facts and Statistics. http://www.leukemia-lymphoma.org/all_page?item_id=12486 Levesque, Michael F. (2005) “Senate Committee Testimony: Spinal Cord Injured Recipient of Adult Stem Cell Therapy”. http://www.leaderu.com/science/stemcelltestimony_levesque.html Lindvall O, Rehncrona S, Brundin P, et al (1989) Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease. A detailed account of methodology and a 6-month follow-up. Archives of Neurology 46: 615-631. Lumelsky N, Blondel 0, Laeng P, Velasco I, Ravin R, and McKay R (2001) Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets. Science 292: 1389-1394. Lunde K, Solheim S, Aakhus S, Arnesen H, et al (2006) Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. The New England Journal of Medicine 355: 1199-1209. Madrazo I, Leon V, Torres C, et al (1988) Transplantation of fetal substantia nigra and adrenal medulla to the caudate nucleus in two patients with Parkinson’s disease. N Engl J Med. 318: 51. Mendez I, Dagher A, Hong M, et al (2002) Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study. Report of three cases. J Neurosurg. 96: 589-596. Perin EC, et al. (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107: 2294-2302.
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Perrier AL, Tabar V, Barberi T, et al (2004) Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci USA. 101: 12543-12548. Quinn NP (1990) The clinical application of cell grafting techniques in patients with Parkinson's disease. Prog. Brain Res. 82: 619–625. Randerson, James (2003) Stem cells fix the damage with heart disease. New Scientist 177: 14. January 11, 2003. Redmond DE, Bjugstad KB, Teng YD, Ourednik V, Ourednik J, Wakeman DR, Parsons XH, Gonzalez R, Blanchard BC, Kim SU, et al. (2007) Behavioral improvement in a primate Parkinson’s model is associated with multiple homeostatic effects of human neuronal stem cells. Proc Natl Acad Sci USA 104: 12175–12180. Rosenstrauch D, Poglajen G, Zidar N, Gregoric ID (2005) Stem cell therapy for ischemic heart failure. Tex Heart Ist J.32: 339–347. Sanberg PR (2007) Neural Stem Cells for Parkinson’s Disease: To Protect and Repair. Proceedings of the National Academy of Sciences 104, 11869–11870.
Santos GW (2000) Historical Background to Hematopoietic Stem Cell Transplantation. In: Atkinson K, ed. Clinical Bone Marrow and Blood Stem Cell Transplantation. Cambridge, UK: Cambridge University Press. pg 1-12. Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, et al. (2006) Intracoronary bone marrow–derived progenitor cells in acute myocardial infarction. The New England Journal of Medicine 355: 1210-1221. Seaberg RM, Smukler SR, Kieffer TJ, et al. (2004) Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22: 1115-1124. Shake JG, Gruber PJ, Baumgartner WA, Senechal G, Meyers J, Redmond JM, Pittenger MF, Martin BJ (2002) Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg. 73: 1919–1926. Siminiak T, Kalawski R, Fiszer D, et al (2004) Autologous skeletal myoblast transplantation for the treatment of post-infarction myocardial injury: Phase I clinical study with 12 months of follow-up. Am Heart J. 148: 531-537. Sipione S, et al. (2004) Insulin-expressing cells from differentiated embryonic stem cells are not beta cells. Diabetologia 47: 499-508. Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49: 157-162. Soria B, Bedoya FJ, Martin F (2005) Gastrointestinal stem cells: I. Pancreatic stem cells. Am J Physiol Gastrointest Liver Physiol, 289: G177-G180.
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“Stem cell transplant works in California case.” Washington Post, April 9, 2002. University Hospitals of Cleveland (2004) Leukemia patients survive with stem cell transplant. ScienceDaily. http://www.sciencedaily.com /releases/2004/11/041129112109.html Wei Z, Chen N, Guo H, Wang X, Xu F, Ren Q, Lu S, Liu B, Zhang L, Zhao H (2009) Bone marrow mesenchymal stem cells from leukemia patients inhibit growth and apoptosis in serum-depraved K562 cells. J Exp Clin Cancer Res. 28: 141. Wild S, Gojka R, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27: 1047-1053.
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Chapter 3: Stem Cell Ethics
World Religions and Stem Cells
Introduction
Stem cell research is important if the medical world wishes to be able to repair damage within
the human body. The past few decades have seen stem cell research develop in amazing ways, many of
which are advantageous to society (as discussed in Chapter-2). But an extremely heated debate still
rages over the use of embryonic (ES) stem cells. And the public often lumps all stem cell types together
confusing adult stem cells with ES cells. The purpose of this chapter is to discuss the ethics of stem cell
use, both adult and embryonic, especially focusing on various religious stances. It is the goal of this
chapter to delve into the particular views of the five major world religions, specifically Christianity,
Judaism, Islam, Buddhism, and Hinduism.
Although both sides of the stem cell dispute have voiced very compelling arguments, the issue is
still embroiled in ethical controversy. The way that ES cells are obtained is central to the debate because
when ES cell lines are created a 5-day old human embryo is destroyed. Thus, the ES cell debate
eventually focuses on when life begins. Those in support of ES cell research say that the moral status of
an early human embryo (5 day old blastocyst) is equivalent to any other cell in the human body, so
destroying it to obtain ES cells is acceptable, especially when trying to save human lives. Those opposed
to ES research state that the embryo is a human life from fertilization, the destruction of which they
consider murder or abortion (Nisbet, 2004). The problem is that both sides believe they are right and
that the other side is wrong. Who should we believe? Is there a way to reach a compromise between the
two groups? These questions have created a basis for religious and secular arguments worldwide.
31
When debating the issue of when life begins, each of the world’s major religions have their own
accounts. Many religious leaders have voiced their stances on the issue of embryo and ES cell research.
For those individuals who inadvertently group all stem cell types into one category, it is important to
note that no major world religion is against using adult stem cells, so long as they are used to try to save
human lives. While using adult stem cells is a relatively placid topic, there is really no consensus
between religions on the acceptability of using embryos or ES cells for research. Because religions have
a duty to respect and protect human life as well as prevent and alleviate suffering, a tension is created in
balancing embryonic stem cell use with the diseases they might cure. Most opinions that deal with the
morality of ES cell research are based upon whether blastocysts are viewed as persons. Some believe
that the early embryos are human persons with human rights from the moment of conception, while for
others the embryo does not reach this stage until anywhere from 40 to 120 days after conception
(Knowles, 2009).
An important point when considering religious views on stem cells is although a particular
religion may hold a particular overall belief, no religion is strictly monolithic and there are many groups
within each religion that may hold contradicting viewpoints. Thus, although a particular religious leader
may hold one stance, other leaders within the same religion may hold different stances.
With respect to the ES cell debate, it is also important to note the source of the embryos used to
derive the ES cells. As discussed in Chapter-1, ES cells are derived from 5-day old blastocysts prepared
by in vitro fertilization (IVF). During IVF, parents donate sperm and eggs to an IVF clinic, and then the
IVF is performed in a test tube. The newly fertilized embryos are grown 5 days to blastocysts and stored
in liquid nitrogen until use. After the parents have enough children, the excess embryos previously
prepared are usually discarded, and it is these discarded embryos (originally prepared for reproductive
purposes) that remain the only legal source of embryos for research in the U.S. even under Obama’s
current favorable legal policies.
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Christianity and Stem Cells
Christianity is the world’s largest religion, and within it are multiple viewpoints on embryo
research. The official position of the Catholic Church on ES cells is that personhood begins at conception
(Catholic Online, 2008). This is taken to mean that the human embryo has the same moral status as a
human person, and deserves the same right to life. Basically it does not matter what the embryos are to
be used for, the end does not justify the means, and the act of killing the embryo at any stage in life is
deemed immoral and unacceptable. However, the Catholic Church wholeheartedly endorses the use of
adult stem cells, also called somatic stem cells, for research (Smith, 2006; Pope Benedict XVI, 2007).
Pope Benedict XVI encouraged those working in Catholic scientific institutions to increase somatic stem
cell research and “to establish closer contact among themselves and others who seek to relieve human
suffering through moral means” (Catholic Online, 2008).
Many members of the Catholic Church have spoken out against embryonic stem cell research.
Perhaps the most major outcry happened in 2001. In response to President Bush’s decision to allow
limited federal funding for embryo stem cell research, Bishop Joseph A. Fiorenza issued a statement
calling the decision morally unacceptable. Pittsburgh Bishop Donald Wuerl also stated that “While a
stem cell is a tiny speck, it nonetheless contains the elements out of which comes the fully developed
human person (American Catholic Organization, 2006).”
As is typical of large religions, multiple viewpoints can exist, and this is the case with Christianity.
While the Catholic Church is clearly against embryo research, other denominations within Christianity,
such as the Unitarian-Universalists, the Episcopal Church, the Evangelical Lutheran Church, the United
Methodist Church, and the Church of Jesus Christ of Latter Day Saints, have no official position
(Derbyshire, 2001).
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Judaism and Stem Cells
Contrary to the Catholic religion, Orthodox Jews believe that early embryos do not have the
same moral status as full human persons. These views are influenced by both biblical and Talmudic
(rabbinical law) (Teaching about Religion, 2006). Actually, under Jewish law, human embryos outside a
human body do not have any rights (Knowles, 2009). Under Jewish Law (Halcha) the fetus does not
become a person (nefesh) until the head emerges from the womb. According to the Talmud, during the
first forty days of gestation, the embryo is “simply water”. Thus, the fetus is only considered “holy” from
the 41st day after conception until birth. During this early period, the Rabbis consider the fetus as the
“thigh of its mother.” Neither men nor women may amputate their thigh because according to the Bava
Kamma, “Our bodies belong to God and hence we are forbidden to inflict injuries upon ourselves.” This
is specifically the period in which the embryo begins to gain its rights (Dorff, 2000). Rabbinical opinions
suggest that the embryo does not reach fetal status until it is implanted in the uterus. Prior to that
implantation, such early embryos have no independent real-life potential, and they are not considered
alive. Consequently, there would be no Jewish legal opposition to disposing of them, researching on
them, or deriving stem cell tissue from them (Jakobovits, 2006). Accordingly, there would also be no
Jewish legal problem using stem cells derived from adult tissues.
In addition to believing an individual’s full rights begin at birth not conception, normative Jewish
law encourages medical interventions to correct both congenital and acquired defects. Thus, many in
Judaism consider it morally wrong not to try to save lives with stem cells. Following these views,
Judaism supports ethically justifiable research using embryos for research and therapeutic purposes
(Teaching about Religion, 2006).
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Islam and Stem Cells
Islamic countries have been involved in stem cell research for several years. Unlike common
perceptions, they are actually more flexible when it comes to human ES cell research than religions such
as Catholicism, because the status of the embryo is different than it is in Christianity. Muslims in Iran,
Turkey, Singapore, and other Islamic countries believe that full human life, including the rights of a
human person, do not begin until after the “ensoulment” of the fetus. Muslim scholars believe this
ensoulment to take place at 120 days after conception (well after the 5 day old blastocyst). In addition,
the importance of preventing human suffering and illness articulated in the Quar’an (similar to Judaism)
means that it is immoral not to try to prevent human suffering, which adds weight to using the surplus
IVF embryos for stem cell research.
And as is typical of any large religion, various viewpoints exist within this one religion. Among
the Muslim community, many different religious leaders and scholars present their opinions, but there is
no singular individual or group that exercises a high authority in all matters of practice (Walters, 2004).
Because of the belief that personhood is an ongoing developmental process, the majority of Sunni and
Shiite jurists support ethically regulated stem cell research (Teaching About Religion, 2006), and it is
generally encouraged if it is being done to produce tissues, valves, and new organs ultimately for
treatment purposes (Bhikkhu, 2007).
Buddhism, Hinduism and Stem Cells
Hinduism is a principal Asian religion that encompasses a vast range of traditions and beliefs.
Hinduism has a lot in common with Buddhism, so they are discussed together here. There is no real
central authority in either religion that can pronounce unified positions on stem cell research, and there
is also no authority that directly addresses the morality of the research. However, because a
35
fundamental tenet of both religions is the importance of practicing compassion towards others, medical
research involving adult stem cells to help others is widely accepted (Knowles, 2009).
For these religions, as with the other main world religions, ES cell research is a controversial
topic. Hindus consider the human embryo to be a person at the moment of conception, because it is
the beginning of a soul’s rebirth from a previous life (Castillo, 2006). In Hinduism, another central tenet
is the mandate to avoid harming other living things. This tenet discourages ES cell research because the
embryo is seen as a living being. However, in some Hindu traditions, the beginning of personhood
begins not at conception, but between three and five months of gestation. A Hindu monk named
Tyaganada best described a perspective on issues related to stem cells. In Hinduism, the soul is the
spiritual component of the personality which is separate from the mind and body; life and death are
inseparable and intertwined. Tyaganada, when describing karma, wrote that the survival of one living
organism is often at the expense of another living creature, thus when the destruction of embryos for ES
cell research is done for the greater good, Hindus will accept ES cell research as ethically justified
(Tyaganada, 2002).
In Buddhism, there are two main tenets similar to Hinduism. These are prohibition against
harming or destroying others (Ahisma), and the pursuit of knowledge (Prajna) and compassion (karua).
These tenets divide Buddhists on the issue of ES cell research (Walters, 2004). On one side, some
Buddhists think that ES cell research fulfills the virtues of seeking knowledge and ending human
suffering. But in stark contrast, other Buddhists believe that it is a violation of harming others (the
embryo). Buddhism agrees with Hinduism on the theory of re-birth and considers any intentional
destruction of embryos to obtain human ES cells as morally not permitted in view of re-birth (Keown,
2001; Keown 2004).
36
Chapter-3 Conclusions
The embryonic stem cell ethical debate has come to center around how a different individuals
view the status of the human embryo. Because some major religions view early embryos as human
beings with full moral rights, they oppose ES cell research. Catholicism, as well as Hinduism and
Buddhism lead this camp by teaching that life begins at conception. The destruction of human embryos
to these religions is akin to murder and euthanasia, because the embryo is considered a living human
person. In contrast, Judaism supports ethically justifiable research using embryos for research and
therapeutic purposes anytime before the 41st day after conception, because of beliefs in their biblical
and Talmudic teachings that ensoulement does not begin until day 40. The majority of Muslims believe
that personhood is an ongoing developmental process, and support the ethically regulated use of ES
cells in research as long as it is being done to create new organs and tissues for treatment purposes and
prior to “ensoulment” at day 120. In general, none of these religions condone research that results in
the destruction of potential human lives, but it is what each religion considers potential human life
which constitutes the difference between their teachings.
Chapter-3 Bibliography
American Catholic Organization (2006) U.S. bishops protest embryo stem-cell research. http://www.americancatholic.org/News/StemCell/bishops_stemcell.asp Bhikkhu DM (2007) Stem cells and the meaning of life. The Record. http://www.therecord.com/NASApp/cs/ContentServer?pagename=record/Layout/Article_Type1&c=Article&cid=1185002166331&call_pageid=1024322088745&col=1024322217916 Castillo D (2006) For faithful, debate rests on origin of life. Columbiamissourian. 26 Apr. 2006. http://www.columbiamissourian.com/stories/2006/04/28/for-faithful-debate-rests-on-origin-of-life/ Catholic Online (2008) Benedict endorses adult stem-cell research as respecting human life. Catholic. http://www.catholic.org/international/international_story.php?id=21301 Derbyshire S (2001) Stop Stemming the Research. http://www.spiked-online.com/Articles/00000002D309.htm
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Dorff E(2000) Stem cell research. Ethical Issues in Human Stem Cell Research, Volume Ill: Religious Perspectives. Jakobovits Y (2006) Judaism and stem cell research. Torah.org. Project Genesis, Inc. http://www.torah.org/features/secondlook/stemcell.html Keown D (2001) Cellular division. Science and Spirit. http://www.science-spirit.org/webextras/keown.html Keown D (2004) “No harm” applies to stem cell embryos: one Buddhist’s perspective. Belief Net. http://www.beliefnet.com/story/143/story_14399_1.html Knowles LP (2009) Religion and stem cell research. Stem Cell Network. http://www.stemcellnetwork.ca/uploads/File/whitepapers/Religion-and-Stem-Cell-Research.pdf Nisbet M (2004) Understanding what the American public really thinks about stem cell and cloning research. Csicop. 2 May 2004. Science and Media. http://www.csicop.org/scienceandmedia/controversy/public-opinion.html Pope Benedict XVI (2007) “Benedict endorses adult stem-cell research as respecting human life”. Catholic Online. http://www.catholic.org/international/international_story.php?id=21301 Smith PJ (2006) Catholic Church NOT Opposed to Stem Cell Research. Catholic Bioethicist. http://www.lifesite.net/ldn/2006/jul/06072709.html Teaching about Religion (2006) General positions on stem cell research and when personhood begins. 18 Mar. 2006. Instructional Systems. http://www.teachingaboutreligion.org/WhatsNew/Stem_cell_research.htm Tyagananda S (2002) Stem cell research: a Hindu perspective. Cache. 24 Apr. 2002. 12 July 2008 http://cache.search.yahoo-ht2.akadns.net/search/cache?ei=UTF-8&p=Hindu+stem+cells&fr=yfp-t-ls+cell&d=Q5SpfC72RDm1&icp=1&.intl=us Walters L (2004) Human embryonic stem cell research: an intercultural perspective. Johns Hopkins University Press. http://muse.jhu.edu/journals/kennedy_institute_of_ethics_journal/v014/14.1walters.html
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Chapter 4: Stem Cell Legalities
U.S. and International Stem Cell Political Policies
Introduction
Stem cell research has risen to become one of the hottest, most highly controversial subjects in
the 21st century. In particular, embryonic stem cells (ESCs) have come to the forefront of most debates
because human embryos are usually destroyed to obtain them. As is typical of any controversial
technology, the debates have influenced the creation of many laws and regulations to govern stem cell
research around the world. In the United States especially, the public has played a huge part in the
politics of the issue, and this topic has truly influenced several of the past elections. The presidencies of
Clinton, Bush, and most recently Obama, have all implemented new policies, aiding or hindering
progress in stem cell research, depending on their ethical beliefs.
U.S. Stem Cell Policies
Most embryonic stem cell research in the past has occurred through in vitro fertilization (IVF).
The IVF embryos are grown about 5 days to the blastocyst stage from which the ES cells are obtained,
which destroys the embryo. During IVF (as discussed in Chapter-3) from its first use in humans in the
early 1960s until now, excess IVF embryos originally created for reproductive purposes were discarded
by the clinic. As science progressed, researchers began to use these discarded embryos to produce new
embryonic stem cell lines. To date, over 100 new embryonic cell lines have been created in the U.S., and
nearly 300 developed in the world, as shown in Figure-10 (Abbott, 2006).
39
Figure 10: World Map Showing the Number of Embryonic Stem Cell Lines Created as of 2006. Each box shows the number of human ES cell lines derived in a country (Abbott et al., 2006).
In 1973, a decision by the United States Supreme Court in Roe v. Wade, to legalize certain types
of abortions, allowed fetal tissue to be used for research purposes and fed the fires of the ethical debate
(Vestal, 2008). In 1979, under President Carter, due to a large amount of pressure from anti-abortion
groups, the Health and Human Services Department disbanded an advisory board that reviewed
federally funded research on human sperm, eggs, and embryos (Smith, 1989). Because of strong anti-
abortion sentiments, Ronald Reagan, and later George Bush, enacted policies to block federal funding
for all research on human embryos (Kleiner, 1994). In the 20 years since, stem cell research policies in
the U.S. have been on a roller coaster ride.
The Clinton Administration
The Clinton administration saw the first real progress made toward uninhibited stem cell
research policies since the initial discovery of the cells. Thirteen years after the Carter Administration
Health and Human Services advisory board (mentioned above) was eliminated, President Clinton
announced that he would lift the ban on embryo research. He gave the National Institutes of Health
40
(NIH) the task of drafting guidelines for studies in this field (Kleiner, 1994). In 1994, the NIH established
the Human Embryo Research Panel to develop methods that researchers should use to obtain embryos,
and to determine the scope of ethical embryo research (Green, 1995). The panel consisted of 19
scientists, physicians, ethicists, lawyers, and community representatives (Green, 1995).
In November of 1994, the panel presented its guidelines. Research could be allowed if the
embryos were less than 14 days old. The research could create IVF embryos solely for research
purposes, and were not limited to surplus embryos from IVF reproductive clinics. The NIH guidelines
were acceptable under the stipulation that the researchers had to show their work promised
outstanding scientific and therapeutic value (Report, 1994). The NIH voted to adopt the guidelines, but
on the day of the vote, President Clinton issued an Executive Order that the scientists could not create
new human embryos solely for research. As a result, researchers could only use embryos left over from
reproductive IVF treatments (Clinton, 1994).
President Clinton strongly supported stem cell research for a reason, both personal and political.
His good friend and chief of staff Erkines Bowles had two children that suffered from diabetes, and
Clinton thought that embryonic stem cell research had the potential to lead to breakthroughs in many
diseases, including diabetes (Clinton, 2004). Many conservatives, however, thought that Clinton’s
decisions were emotionally driven because of this, and did not think that he had the scientific working
knowledge of stem cells to make such claims.
In 1995, Congress overrode certain aspects of Clinton’s decision, preventing NIH from funding
any research that harms or destroys human embryos (Vestal, 2008). Clinton’s response was to tell the
country that he did not approve of the direction congress was taking the research.
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The Bush Administration
In 2001, the election of George W. Bush brought many changes to stem cell research. Being a
devout Christian (and strongly influenced by the Catholic Pope), he firmly believed that life begins at
conception with the very early human embryo (Dunn, 2005). His religion became a dominant force
during his presidency that influenced him against the advancement of stem cell research. On August 9,
2001, President Bush announced that he would not allow any federal funding to derive new embryonic
stem cell lines after that date (Pizzi, 2002). This put up a huge barrier for embryonic stem cell
researchers because they could no longer afford to derive new ES cell lines on their own, so they had to
obtain their embryos from private companies. Three months later, the Bush administration ordered an
official withdrawal of funding guidelines that President Clinton had authorized. In doing this, he became
the first president to reduce the amount of legal stem cell research from what the previous president
had established (Dunn, 2005). Bush continued to shoot down any legislation that would loosen his
restrictive guidelines on stem cell research. He issued presidential vetoes on two separate occasions,
one in response to a 2006 vote by the U.S. Senate to overturn his 2001 law, and the next in 2008 in
response to another bill from the Senate to enhance stem cell research (Johnson & Williams, 2006).
President Bush held firmly in his beliefs that ES cell research is not moral and the destruction of human
life for research will not be tolerated.
Individual States Stem Cell Policies
During the Bush administration, there were many clashes between the President and Congress
over stem cell research. But that did not stop the advancement of stem cell research. One could even
say that Bush’s vetoes over the Senate led to local innovations in stem cell research. After dealing with
the federal ban for many years, individual states began to allocate huge amounts of money into their
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own research. Most notably, California and Massachusetts, have poured immense sums of money into
stem cell research, although the total dollars can not match what the federal government can do.
In November 2004, voters in California passed Proposition 71 to fund adult and embryonic stem
cell research, and to establish the International Stem Cell Institute in San Francisco. The proposition
authorized the issuance of state bonds in the amount of $3 billion, beginning in 2005, not to exceed sale
of over $350 million per year. Although this state proposition remains one of the most ambitious of the
various states seeking funding, and some Training Grants have been awarded, the award of larger
research grants has been slowed by litigation. As a result, the Governor of California decided to loan the
International Stem Cell Institute $150 million in August 2006, and the institute continues to seek
proposals. The California Institute of Regenerative Medicine (CIRM), which administers the state stem
cell research program, developed a Scientific Strategic Plan which was approved by its governing board
in December2006. It is estimated that CIRM spent over $622 million through the fiscal year 2008-09
(Hayden, 2008).
In Massachusetts, after overriding Governor Mitt Romney’s veto of a measure aimed at
supporting human embryonic stem cell research in the state, Massachusetts legislators added two new
sections to the statutes on stem cell research (Massachusetts… 2005). The first statute created an
Institute for Stem Cell Research and Regenerative Medicine at the University of Massachusetts Medical
Center (Worcester), with an appropriation of $1,000,000 to be spent on the stem cell biology core. The
second statute established a Life Sciences Center to promote life sciences research in advanced and
applied sciences, including but not limited to stem cell research, regenerative medicine, biotechnology,
and nanotechnology. The statute also created the Life Sciences Investment Fund to make
appropriations, allocations, grants or loans to leverage development and investments in stem cell
research and other areas. $10,000,000 was appropriated to the fund. Massachusetts is now a leading
force in stem cell research in the U.S.
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In order for stem cell research to advance, more trained scientists need to be trained in the
United States. Fortunately, many individual state’s bonds directly support scientist trainings in stem
cell research, which indirectly overturns the federal veto by President Bush.
Current U.S. Stem Cell Policies under the Obama Administration
In January 2009, President Barack Obama was inaugurated and ushered in a new era of stem cell
research. Researchers whose work had been shackled during the 8 long years of Bush’s administration
finally rejoiced when Obama signed an executive order for the NIH to develop guidelines and regulations
to govern federally funded human embryonic stem cell research. He stated that “We will vigorously
support scientists who pursue this research, and we will aim for America to lead the world in the
discoveries it one day may yield” (Hayden, 2009). He also stated that “At this moment, the full promise
of stem cell research remains unknown, and it should not be overstated, but scientists believe that these
tiny cells may have the potential to help us understand, and possibly cure, some of our most devastating
diseases and conditions” (Childs & Stark, 2009).
The changes that just occurred in the US Federal Administration following the election of
President Obama are substantial and important. Given the new federal administrative backing, there will
be an escalation of clinical trial submissions involving pluripotent ESCs, multipotent placental, and adult
and fetal stem cells. The need for new investments for clinical trial support will be a key bottleneck,
unless the government and health insurance industry joins pharmaceutical and biotechnology industries
to carry out the large variety of trials expected. Academic and medical research centers are also
expected to be involved in the translation and clinical trial processes which heralds new opportunities
for teamwork approaches for these new cell therapies (Trounson, 2009).
The NIH estimates the number of new embryonic stem cell lines to be anywhere from 400 to
1000. These lines are vastly different from the 21 lines originally eligible for federal funding during the
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Bush administration. A large amount of these new lines have been created from embryos with genetic
predispositions to specific diseases making them much more relevant to preclinical studies (Hayden,
2009). In July 2009, the NIH approved its modified guidelines for stem cell research. One key debate
point was the source of the embryos. Most scientists wanted federal funding for IVF embryos created
solely for research purposes, but the final recommendation (in a nod to their ethically sensitive nature)
was to allow only excess IVF embryos created for reproductive purposes.
The public apparently supports these recent developments in stem cell legislation, as a majority
(currently 57%) have no qualms about ES cell research (Figure-11).
Figure 11: Gallup Poll Summary of Americans in Favor of ES Research. American public opinion on medical research using stem cells obtained from human embryos (Good, 2009).
From tiny embryonic cells, to the large-scale physics of global warming, President Barack Obama
urged researchers in 2009 to follow science and not ideology as he abolished contentious Bush-era
restraints on stem-cell research. Obama’s message was clear; Science, which once propelled men to the
moon, again matters in American life (Borenstein & Feller, 2009).
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International Stem Cell Policies
Although the United States is a big name in stem cell research, the rest of the world also has
some key players, and continues to expand their research. Some say that the U.S. is falling behind other
nations (Schmickle, 2008), so hopefully this will change under the Obama administration. Many top U.S.
researchers in the past decade moved to the U.K. because of their wide-open race to develop stem cells.
Below in Figure-12 is a map of the globe showing the policies of various countries on stem cell research.
Figure 12: Global Stem Cell Policies. Shown is a global map denoting the location of various stem cell centers (black dots), as well as the stem cell policies (Hoffman, 2007).
A number of countries are emerging as powerhouses in the field of stem cell research. These
include Great Britain, Australia, Sweden, and China. Great Britain is the leader in embryonic stem cell
research and has been for years. This is largely due to effective regulation, which allows various forms
of ES cell research, and instills a trust between scientists and the public. Early on, Great Britain viewed
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stem cell research as a lucrative opportunity, and took advantage of the scientific opportunity. In the
1980s, British Parliament organized a committee to specifically address stem cell ethical concerns and
scientific research limitations. The committee came to the conclusion that, “Scientists can ethically, use
early embryos for research purposes, but any such research work should be strictly regulated.” Since
then they have continued to grow (Boyd et al., 2009).
In 2002, Australia founded the Australian Stem Cell Centre to take advantage of the country’s
significant strengths in the field of stem cell research. They passed the Research Involving Human
Embryos Act in 2002, which allowed for research on excess IVF embryos, including using them to derive
human embryonic stem cells. Since then, they have derived over 30 separate embryonic stem cell lines
(Stem Cell Research in Australia, 2009).
Sweden has long been a world leader in stem cell research. The main difference between
Sweden and the U.S. is that it never had any difficulty allowing ES cell lines to be derived from excess IVF
embryos. This is now allowed in the U.S. with federal funding because of the Obama Administration’s
policies, but research was delayed for almost 10 years while Sweden continued throughout.
With generous support and in a cultural environment where there are fewer moral dilemmas to
using embryonic stem cells, China has been booming with research. In 2002, scientists developed a
method to genetically alter neural stem cells to reproduce indefinitely but still retain their ability to
differentiate into neurons. China is rapidly advancing in the field of regenerative medicine, hoping to use
stem cell research to cure and treat a myriad of diseases afflicting people across the globe. They were
also the first country to conduct human stem cell trials, and presented a significant opportunity for
Western companies who were brave enough to use a risky destination as a place to pursue the
potentially lucrative sector of their biotech industry (Barnes, 2006).
Hopefully under Obama’s new policies, any initial brain drain that may have started with U.S.
scientists migrating to other countries has been halted. However, real brain drains have occurred within
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the U.S. as some top scientists migrated to Calilfornia and Massachusetts from other states not funding
ES cell research during the Bush administration.
Chapter-4 Conclusion
In the past 30 years, we have seen stem cell research grow in leaps and bounds, but obviously
this controversial technology has mandated laws that regulate its use. I feel that in order to effectively
mediate stem cell research, a country must completely support and maintain funding for the research at
the federal level. Although individual states can fill in from time to time, nothing moves an agenda
forward faster than with federal approval. In the United States, progress on stem cell research has
directly reflected the elected administration at the time, and has had periods of less growth. Since the
Presidency changes so frequently compared to other countries, and holds strong powers with its
executive vetos, the President’s views have had a strong effect on research. In order for the United
States to keep up with the rest of the world, Obama’s current favorable stem cell regulations must be
maintained even in subsequent administrations, scientific eduction of the public must continue
(including with this IQP project), and researchers and industry need to collaborate to fund expensive
stem cell clinical trials.
Chapter-4 Bibliography
Abbott A, Dennis C, Ledford H, and Smith K (2006) The lure of stem cell lines. Nature 442: 336-337. Barnes C (2006) China the land of opportunity for stem cell research. DrugResearcher.com. 1 Jun 2006. http://www.drugresearcher.com/Research-management/China-the-land-of-opportunity-for-stem-cell-research Borenstein S, Feller B (2009) Obama science memo goes beyond stem cells. The Huffington Post. 9 Mar 2009. http://www.huffingtonpost.com/2009/03/09/obama-science-memo-goes-b_n_172987.html Boyd C, Magistad MK, Schachter A (2009) The global race for stem cell therapies. Public Radio International. http://www.pri.org/theworld/?q=node/3607.
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Childs D, Stark L (2009) Obama reverses course, lifts stem cell ban. ABC News. 9 Mar. 2009. http://abcnews.go.com/Health/Politics/story?id=7023990&page=1 Clinton B (2004) My life, by Bill Clinton: on abortion. On the Issues. http://www.ontheissues.org/archive/my_life_abortion.htm Clinton WJ (1994) Statement by the President. http://www.pub.whitehouse.gov Dunn K (2005) The politics of stem cells. NOVA Science Now. April 14, 2005. http://www.pbs.org/wgbh/nova/sciencenow/dispatches/050413.html Good C (2009) Stem cell polling: support has steadily grown. Politics: The Atlantic. March 9, 2009. http://politics.theatlantic.com/2009/03/stem_cell_polling_support_has_steadily_grown.php Green RM (1995) The ban on embryo research hurts U.S. health. Newsday A34. Hayden EC (2008) The 3-Billion Dollar Question. Nature 453: 18-21. Hayden EC (2009) Obama Overturns Stem Cell Ban. Nature 458: 130-131. Hoffman W (2007) World stem cell policy map. MBBNet. http://www.mbbnet.umn.edu/scmap.html Johnson JA, Williams ED (2006) Stem Cell Research. CRS Report for Congress. http://www.usembassy.it/pdf/other/RL31015.pdf Kleiner K (1994) US to sanction embryo research. New Scientist 144: 5. Massachusetts Stem-Cell Bill Becomes Law Despite Veto (2005) Public Health. Daily News Central. 1 June 2005. http://health.dailynewscentral.com/content/view/000929/44 Pizzi RA (2002) The science and politics of stem cells. Modern Drug Discovery 5: 32-34, 36-37. Report of the Human Embryo Research Panel (September 27, 1994) Rockville, MD, National Institutes of Health. Schmickle S (2008) Stem cell stalemate: Minnesota authors say U.S. falling behind other nations. Minn Post. 25 Mar 2008. http://www.minnpost.com/stories/2008/03/25/1258/stem_cell_stalemate_minnesota_authors_say_us_falling_behind_other_nations Smith ET (1989) Will Washington resume funding embryo research? Business Week 127. Stem Cell Research in Australia (2009) Australian Stem Cell Centre Ltd. http://www.stemcellcentre.edu.au/file_downloads/fact_sheets/ascc_fact4_research.pdf Trounson A (2009) New perspectives in human stem cell therapeutic research. BMC Medicine 7: 29.
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Vestal C (2008) Stem cell research at the crossroads of religion and politics. The Pew Forum on Religion and Public life. http://pewforum.org/docs/?DocID=316
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PROJECT CONCLUSIONS
After researching the information for this IQP, I have developed several opinions
regarding the use of stem cells. With regards to embryonic stem (ES) cells, I firmly believe that
it is acceptable to work them because of the near limitless potential and applications they have
for disease treatment and regenerative medicine. As long as ES cells continue to be an extremely
controversial topic in society, I do agree with other researchers that adult stem cells (ASCs)
should be used wherever possible, as long as they provide similar medical results to ES cells.
One foreseeable problem with ASCs is that they are currently very hard to produce in mass
quantities. If the limitations of ASC production hamper the treatment of a particular disease, I
believe that ES cells should be used instead. When ES cells are used, I believe they should be
obtained from excess IVF embryos originally created for reproductive purposes, not from paid
donors created solely for research purposes. Because the excess IVF embryos have donor
consent, and are going to be destroyed anyways, the rest of society should benefit from them,
instead of letting a valuable potential go to waste. With respect to stem cell legislation,
worldwide Sweden currently has the best policies supporting stem cells, and that country is
considered a leader in the field. In the U.S., hopefully with the recent favorable stem cell
legislation under the Obama administration, and a continuation of these policies from this
president to the next, the United States can remain one of the world leaders in the medicine of
the 21st century.
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