Strictly speaking, a stem cell is derived from the inner cell mass of an egg 4 days after fertilization, is capable of indefinite reproduction, and is independently capable of generating every tissue that ultimately constitutes an adult organism. These powerful properties have launched stem cells into the forefront of a revolution that offers to change the way doctors treat degenerative diseases and scientists approach fundamental questions of development, birth, degeneration and death. ( Steinbock, 1992)
Recently, the term stem cell has also been applied
(somewhat more loosely in the eyes of purists)
to cells derived from adult animals and humans.
The presence of these so-called adult stem cells
has been known since 1998. They can be identified
and harvested from adult animal and human organs
such as heart, muscle, brain, blood or bone marrow
and can actually be cultured in the laboratory.
Not only that, these adult stem cells have the
ability to propagate for long periods of time
in the laboratory while retaining their ability
to differentiate into the tissues from which they
were initially harvested under certain conditions.
( Thomson, 1998)
The earliest investigators demonstrated convincingly that the bone marrow of mice housed specialized cells known as "satellite cells" that migrated to the skeletal muscle when it was injured (and only when it was injured) and participated in a regenerative process that restored the injured muscle almost back to complete health. This finding has unleashed the hope of tremendous potential that such cells could be harvested and expanded in culture and therefore be applied to cure the damage inflicted by degenerative human conditions such as heart attacks, stroke, diabetes, Alzheimer's disease, wasting bone diseases such as osteogenesis imperfecta, and muscle conditions such as muscular dystrophy. In doing so, clinicians would be following the same paradigm established by colleagues that had developed strategies for repopulating the bone marrow that has been destroyed by high-dose chemotherapy. ( Shamblott, 1998)
Indeed, the successes that researchers have
had in the isolation of human adult stem cells
(and with resultant clinical application) have
been astounding, with 3,600 scientific papers
written on the subject in 2003 alone. Investigators
from all over the world have claimed that adult
human stem cells can differentiate into structures
as varied as liver, pancreas, intestine, brain
tissue, heart, bone, cartilage and even fat. Not
only that, the literature is replete with claims
that these cells demonstrate remarkable plasticity,
the ability to trans-differentiate from one structure
into a completely unrelated structure. For example,
fat cells have been shown to differentiate into
blood vessels, muscle, cartilage and bone. Researchers
would caution that the reproducibility of a lot
of these claims is yet to be determined in rigorous
peer-reviewed fashion.
The claims of dramatic tissue plasticity are probably inflated to some degree, and remain concerned that the true mechanisms of action by which these cells improve function are unknown. All the early clinical data emerging in the medical literature suggest that efficacy of adult stem cell implantation in human subjects, using current techniques and available small numbers of cells, is uncertain at best. Most of the parameters in which improvement is seen are subjective (raising the issue of powerful placebo effects), and true objective measures of improvement are lacking.
As long as absolute restrictions on the use of human embryonic stem cells for research exist, scientists cannot study these questions. Unfortunately, the embryonic stem cell question has been manipulated into a surrogate for America's argument over the ethics of elective abortion, although the strategies for embryonic cell extraction and elective abortion are distinct. ( Steinbock, 1992)
There are three strategies for deriving a totipotent
stem cell. The first is to extract them from very
early human embryos, and is a strategy that was
first explored by investigators at the University
of Wisconsin in the 1990s. Human embryos created
in IVF clinics were donated to investigators by
couples that did not want to use them for purposes
of "creating a child," and a series
of human embryonic stem cell lines were successfully
created and exist to this day. ( Shamblott, 1998)
Current United States law prohibits the use of federal funds for the creation of a human embryo for research purposes or for research in which human embryos are destroyed, discarded or knowingly subjected to risk, injury or death that is greater than that allowed for fetuses in utero. Accordingly, there is no role for clinical or basic scientific research as it applies to these embryos.
The numbers involved here are staggering. Only 10 percent of transferred embryos actually produce a baby, and over 120,000 of these procedures were performed in the USA in 2001, leaving us with an excess of 100,000 embryos each year that remain frozen in IVF facilities across America with no consideration for their moral position, role in society, or future use.
One pole of this debate views the creation and manipulation of living human embryos for the sole purpose of generating therapeutic tissue as incompatible with respect for vulnerable human life with opprobrium.
Researchers believe there is a distinct moral position between creating and destroying an embryo for research purposes to obtain stem cells exclusively versus using an embryo that was created for reproduction but will never be used for any purpose. In addition, well-developed fetuses and embryos can be argued to not share equal moral status, given the limited potential that pre-implantation embryos have to become fetuses and, therefore, adults. In fact, over 99 percent of such pre-implantation embryos are thought to be lost in a miscarriage even before the first menstrual period is missed. ( Steinbock, 1992)
The second technique is to extract human embryonic
stem cells from 5-9-week-old aborted fetuses,
an approach wrought with near-insurmountable ethical
controversy in the current social and political
climate in our country. Such a strategy is unlikely
to add significant benefit over the use of in
vitro fertilization embryos.
The third technique, also known as "cloning," is to derive embryonic stem cells via somatic cell nuclear transfer. A complete set of genetic material (all 46 chromosomes that reside within the nucleus of a somatic cell) is transferred into an enucleated female egg (which normally contains half the total complement of chromosomes).
Theoretically, once this egg "sees" a full set of chromosomes (as it would after fertilization by a male gamete), it would set into motion a series of events that allow maturation of that cell into an embryo. This is the technique whereby the sheep "Dolly" was cloned by British investigators in the 1990s. This procedure needs a large supply of eggs, is time consuming, labor intensive, and expensive. Because the supply of eggs is limited, and the demand is great, coercion and financial incentives to donate eggs are commonplace in our country, even though such incentives are banned in Europe. This process has been performed in a human being in South Korea, and was approved for human use in the U.K. on August 12, 2004, under the auspices of the Human Fertilization and Embryology Authority.
The scientific concerns behind such strategies are based on experiences with animal studies, in which the animals are abnormal and have unusual DNA methylation patterns and genomic imprinting. Moreover, these animals age rapidly and die chronologically premature (but physiologically normal) deaths, and we don't know why. Sadly, even a promising technology such as this has been hijacked by fringe groups (such as Clonaid) for popular gain and has generated fear in the popular media of the cloning of genetically modified human beings, and the generation of embryos for spare parts--reducing human life to purely utilitarian values.
Arguments in Favor of Stem Cell Research
Even though no clinical studies have been performed,
from a purely scientific standpoint, embryonic
stem cells offer scientists greater opportunities
than adult stem cells do. These include the chance
to study development of organisms and the processes
that lie behind appropriate growth, maturation,
and senescence. Scientists would be able to identify
precursor cells-- cells that are no longer
stem cells but have the ability to differentiate
into certain lineages--perhaps allowing scientists
to one day circumvent having to harvest stem cells.
( Thomson, 1998)
Moreover, embryonic stem cells allow scientists to identify genes that are involved in the processes outlined above. Given the inextricable links between mistakes in development and disease, such approaches would give scientists the ability to identify genes involved in illness, identify potential therapeutic targets for gene and drug therapy, and allow scientists to test drugs for toxicity on certain cell types, thereby obviating the need for extensive animal testing that has little relevance to human application. In addition, embryonic stem cells allow scientists to develop a high-throughput functional testing strategy for drugs and gene therapy, which should accelerate delivery of more effective and less expensive medications for human use. ( Shamblott, 1998)
The idea of viability in obstetrics and in infertility
is meaningful as a measure of whether a preordained
goal, namely conception and birth, is possible
under some particular circumstance. Researchers
typically learn about the development of fetuses
and embryos, and about the potential of germ cells
and stem cells, only within the context of the
goal of controlling reproductive activity. Researchers
define success in pregnancy, and it means "delivery
with the minimum amount of complication and the
maximum amount of fetal flourishing." Viability
is really a measure of the capacity of present
technology to ensure the kind of successful ends
we hold. When scientists note that approximately
8 percent of all conceptions in the womb result
in miscarriage and thus were not viable pregnancies,
scientists mean that in those cases there was
no remedy within our grasp for whatever caused
the miscarriage.
New technologies change the idea of viability by giving more and more embryos, tissues, cells, and fetuses the potential to turn out the way scientists want them to. When whole classes of tissues or cells can be reclassified in that way, the very idea of a viable pregnancy can change. If a somatic cell can now be transplanted into an enucleated egg and the resultant renucleated egg jarred into behaving like an embryo, one might say the resultant thing has the potential for reproductive viability, even though no conception was involved. If a large number of such renucleated eggs behave like embryos and when implanted do not spontaneously abort at a rate greater than that of "ordinary" embryos, one might well elect to say that they are viable--indeed that they are embryos. In every case, the meaning of viability is subject to the evolving nature of one’s technologies and the evolving set of purposes to which they can be put.
Arguments Against Stem Cell Research
Nevertheless, it would be shortsighted to claim that adult stem cells are a panacea. These cells are notoriously elusive and difficult to find. Their characterization has been challenging at best, and remains incomplete. They are harvested in small numbers and often need to be propagated in tissue culture for long periods of time, which is impractical from a clinical standpoint, and can lead to potentially damaging changes. The cells are difficult to harvest, and often require damage to the host organ, which is awkward if they are to be used clinically for regeneration of the same organ!
Even more critically, if these cells are being used in the clinical setting for autologous regeneration, they may actually carry the same genetic flaws that predisposed the host organism to the disease process in the first place. ( Thomson, 1998)
Embryonic stem cell use comes with its own set
of unique limitations. Donor-recipient incompatibility
is a major concern, but can be potentially circumvented
by banking large numbers of human embryonic stem
cells so at least one could work for you, or by
genetically modifying them to resist immune challenges.
New discoveries in stem cell biology will soon bring revolutionary changes in the way physicians approach degenerative diseases, wound repair, autoimmune conditions, cancer, and reproductive medicine. Stem cells are self-renewing cells capable of producing many different cell types. Adult stem cells do well in repairing their organ of origin but have limited capabilities in self-renewal and distant organ repair under normal physiologic conditions. The degree plasticity potential of the adult stem cell has yet to be determined. Embryonic stem cells have tremendous therapeutic and research potential to produce any tissue of the body and to grow unperturbed in plastic culture dishes for many years. ( Thomson et al, 1998; Shamblott et al, 1998) . Stem cells currently are used in transplantation regimens to repair wounded organs. They are also used experimentally in toxicity studies to test drug safety, cancer investigations to pinpoint methods of unregulated growth, and reproductive protocols to identify critical stems in fertility and pregnancy. However, along with these remarkable abilities, use of stem cells carries many ethical challenges.
Many religious perspectives consider the human
fetus to constitute an individualized human entity.
However, there is substantial debate regarding
at which specific stage dignity is conferred in
development (conception, primitive streak development,
implantation, quickening, or birth) ( Athenagoras
, 177 AD; Humane Vitae , 1968) Recently, a less
specific developmental view of moral status surfaced,
meriting moral rights to the individual as consciousness
and relationships develop. (Steinbock, 1992; Warren,
1997)
Taking into account the many perspectives on the moral status of the human embryo and the scientific promises of a healthier tomorrow through stem cell technology, our society has attempted to define the legal status of the human embryo. In the United States, the first pillar was constructed in 1973 when the US Supreme Court ruled that a fetus is not a person in terms of constitutional protection (Roe v Wade, 410 US 113 [1973]). For a better examination of the decision’s effect on research, the National Institutes of Health (NIH) imposed a moratorium on fetal research, and Congress founded the National Commission, charged to put together policy and guidelines on fetal research. Four months later, the commission published a report encouraging fetal research because of its potential, provided that the research risks to the fetus were minimal and were only those that would be accepted for a term fetus. ( Report And Recommendations , 1975) Thus, despite Roe v Wade, the commission extended protection to a fetus (just as to adult patients) in research, including fetuses planned for elective abortion.
The NIH moratorium was lifted in 1975. However, during President Ronald W. Reagan’s second term, Congress enacted legislation that further protected the fetus by ending federal support of fetal research involving any level of risk. ( Protection of Human Subjects, 1985) In 1996, Congress extended this restriction by banning federal funding for the creation of a human embryo for research purposes. This led the NIH to distinguish between deriving and using existing human embryos to support embryonic stem cell research. Under these guidelines, researchers using already established hES cell lines derived from private sector support can receive public sector monies, provided that the fertilized embryos would otherwise have been discarded after IVF or were from already aborted fetuses, donors are aware of the research use, and no payment was made to the donors. (Athenaoras, 177 AD)
The National Bioethics Advisory Commission (NBAC) was charged by President William J. Clinton to thoroughly review moral and legal issues of stem cell research. ( National Bioethics Advisory Commission , 1999) This commission largely framed its moral position based on a utilitarianism argument- the good of many outweigh the status of one. In addition, it drew on medicine’s aims to heal and prevent disease, urging consideration of a long-term benefit-to-harm balance. In the end, the NBAC recommended allowing federal funding for hES research on excess IVF embryos.