Stem cell controversy

The stem cell controversy is the consideration of the ethics of research involving the development, use, and destruction of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves the human embryos. For example, adult stem cells, amniotic stem cells, and induced pluripotent stem cells do not involve creating, using, or destroying human embryos, thus are minimally, if at all, controversial. Many less controversial sources of acquiring stem cells include using cells from the umbilical cord, breast milk, and bone marrow, which are not pluripotent.

Background

For many decades, stem cells have played an important role in medical research, beginning in 1868 when Ernst Haeckel first used the phrase to describe the fertilized egg which eventually gestates into an organism. The term was later used in 1886 by William Sedgwick to describe the parts of a plant that grow and regenerate. Further work by Alexander Maximow and Leroy Stevens introduced the concept that stem cells are pluripotent, i.e. able to become many types of different cell. This significant discovery led to the first human bone marrow transplant by E. Donnal Thomas in 1968, which although successful in saving lives, has generated much controversy since. This has included the many complications inherent in stem cell transplantation (almost 200 allogeneic marrow transplants were performed in humans, with no long-term successes before the first successful treatment was made), through to more modern problems, such as how many cells are sufficient for engraftment of various types of hematopoietic stem cell transplants, whether older patients should undergo transplant therapy, and the role of irradiation-based therapies in preparation for transplantation.

The discovery of adult stem cells led scientists to develop an interest in the role of embroynic stem cells, and in separate studies in 1981 Gail Martin and Martin Evans derived pluripotent stem cells from the embryos of mice for the first time. This paved the way for Mario Capecchi, Martin Evans, and Oliver Smithies to create the first knockout mouse, ushering in a whole new era of research on human disease.

In 1998, James Thomson and Jeffrey Jones derived the first human embryonic stem cells, with even greater potential for drug discovery and therapeutic transplantation. However, the use of the technique on human embryos led to more widespread controversy as criticism of the technique now began from the wider non-scientific public who debated the moral ethics of questions concerning research involving human embryonic cells.

Potential use in therapy

Since pluripotent stem cells have the ability to differentiate into any type of cell, they are used in the development of medical treatments for a wide range of conditions. Treatments that have been proposed include treatment for physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). Yet further treatments using stem cells could potentially be developed due to their ability to repair extensive tissue damage.^[1]

Great levels of success and potential have been realized from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. These can become any cell type of the body, excluding placental cells. This ability is called pluripotency. Only cells from an embryo at the morula stage or earlier are truly totipotent, meaning that they are able to form all cell types including placental cells. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become.

Points of controversy

Many of the debates surrounding human embryonic stem cells concern issues such as what restrictions should be made on studies using these types of cells. At what point does one consider life to begin? Is it just to destroy an embryo cell if it has the potential to cure countless numbers of patients? Political leaders are debating how to regulate and fund research studies that involve the techniques used to remove the embryo cells. No clear consensus has emerged. Other recent discoveries may extinguish the need for embryonic stem cells.^[2]

Much of the criticism has been a result of religious beliefs, and in the most high-profile case, Christian US President George W Bush signed an executive order banning the use of federal funding for any cell lines other than those already in existence, stating at the time, "My position on these issues is shaped by deeply held beliefs," and "I also believe human life is a sacred gift from our creator."^[3] This ban was in part revoked by his successor Barack Obama, who stated "As a person of faith, I believe we are called to care for each other and work to ease human suffering. I believe we have been given the capacity and will to pursue this research and the humanity and conscience to do so responsibly." ^[4]

Potential solutions

Some stem cell researchers are working to develop techniques of isolating stem cells that are as potent as embryonic stem cells, but do not require a human embryo.

Foremost among these was the discovery in August 2006 that adult cells can be reprogrammed into a pluripotent state by the introduction of four specific transcription factors, resulting in induced pluripotent stem cells.^[5] This major breakthrough won a Nobel Prize for the discoverers, Shinya Yamanaka and John Gurdon.^[6]

In an alternative technique, researchers at Harvard University, led by Kevin Eggan and Savitri Marajh, have transferred the nucleus of a somatic cell into an existing embryonic stem cell, thus creating a new stem cell line.^[7]

Researchers at Advanced Cell Technology, led by Robert Lanza and Travis Wahl, reported the successful derivation of a stem cell line using a process similar to preimplantation genetic diagnosis, in which a single blastomere is extracted from a blastocyst.^[8] At the 2007 meeting of the International Society for Stem Cell Research (ISSCR),^[9] Lanza announced that his team had succeeded in producing three new stem cell lines without destroying the parent embryos. "These are the first human embryonic cell lines in existence that didn't result from the destruction of an embryo." Lanza is currently in discussions with the National Institutes of Health to determine whether the new technique sidesteps U.S. restrictions on federal funding for ES cell research.^[10]

Anthony Atala of Wake Forest University says that the fluid surrounding the fetus has been found to contain stem cells that, when used correctly, "can be differentiated towards cell types such as fat, bone, muscle, blood vessel, nerve and liver cells". The extraction of this fluid is not thought to harm the fetus in any way. He hopes "that these cells will provide a valuable resource for tissue repair and for engineered organs, as well".^[11]

Viewpoints

The status of the human embryo and human embryonic stem cell research is a controversial issue, as with the present state of technology, the creation of a human embryonic stem cell line requires the destruction of a human embryo. Most of these embryos are discarded. Stem cell debates have motivated and reinvigorated the pro-life movement, whose members are concerned with the rights and status of the embryo as an early-aged human life. They believe that embryonic stem cell research instrumentalizes and violates the sanctity of life and is tantamount to murder.^[12] The fundamental assertion of those who oppose embryonic stem cell research is the belief that human life is inviolable, combined with the belief that human life begins when a sperm cell fertilizes an egg cell to form a single cell. The view of those in favor is that these embryos would otherwise be discarded, and if used as stem cells, they can survive as a part of a living human being.

A portion of stem cell researchers use embryos that were created but not used in in vitro fertility treatments to derive new stem cell lines. Most of these embryos are to be destroyed, or stored for long periods of time, long past their viable storage life. In the United States alone, an estimated at least 400,000 such embryos exist.^[13] This has led some opponents of abortion, such as Senator Orrin Hatch, to support human embryonic stem cell research.^[14] See also embryo donation.

Medical researchers widely report that stem cell research has the potential to dramatically alter approaches to understanding and treating diseases, and to alleviate suffering. In the future, most medical researchers anticipate being able to use technologies derived from stem cell research to treat a variety of diseases and impairments. Spinal cord injuries and Parkinson's disease are two examples that have been championed by high-profile media personalities (for instance, Christopher Reeve and Michael J. Fox, who have lived with these conditions, respectively). The anticipated medical benefits of stem cell research add urgency to the debates, which has been appealed to by proponents of embryonic stem cell research.

In August 2000, The U.S. National Institutes of Health's Guidelines stated:

...research involving human pluripotent stem cells...promises new treatments and possible cures for many debilitating diseases and injuries, including Parkinson's disease, diabetes, heart disease, multiple sclerosis, burns and spinal cord injuries. The NIH believes the potential medical benefits of human pluripotent stem cell technology are compelling and worthy of pursuit in accordance with appropriate ethical standards.^[15]

In 2006, researchers at Advanced Cell Technology of Worcester, Massachusetts, succeeded in obtaining stem cells from mouse embryos without destroying the embryos.^[16] If this technique and its reliability are improved, it would alleviate some of the ethical concerns related to embryonic stem cell research.

Another technique announced in 2007 may also defuse the longstanding debate and controversy. Research teams in the United States and Japan have developed a simple and cost-effective method of reprogramming human skin cells to function much like embryonic stem cells by introducing artificial viruses. While extracting and cloning stem cells is complex and extremely expensive, the newly discovered method of reprogramming cells is much cheaper. However, the technique may disrupt the DNA in the new stem cells, resulting in damaged and cancerous tissue. More research will be required before noncancerous stem cells can be created.^{[17][18][19][20]}

Update article to include 2009/2010 current stem cell usages in clinical trials.^[21][22] The planned treatment trials will focus on the effects of oral lithium on neurological function in people with chronic spinal cord injury and those who have received umbilical cord blood mononuclear cell transplants to the spinal cord. The interest in these two treatments derives from recent reports indicating that umbilical cord blood stem cells may be beneficial for spinal cord injury and that lithium may promote regeneration and recovery of function after spinal cord injury. Both lithium and umbilical cord blood are widely available therapies that have long been used to treat diseases in humans.

Endorsement

• Embryonic stem cells have the potential to grow indefinitely in a laboratory environment and can differentiate into almost all types of bodily tissue. This makes embryonic stem cells a prospect for cellular therapies to treat a wide range of diseases.^[23]

Human potential and humanity

This argument often goes hand-in-hand with the utilitarian argument, and can be presented in several forms:

• Embryos are not equivalent to human life while they are still incapable of surviving outside the womb (i.e. they only have the potential for life).
• More than a third of zygotes do not implant after conception.^[24][25] Thus, far more embryos are lost due to chance than are proposed to be used for embryonic stem cell research or treatments.
• Blastocysts are a cluster of human cells that have not differentiated into distinct organ tissue, making cells of the inner cell mass no more "human" than a skin cell.^[23]
• Some parties contend that embryos are not humans, believing that the life of Homo sapiens only begins when the heartbeat develops, which is during the fifth week of pregnancy,^[26] or when the brain begins developing activity, which has been detected at 54 days after conception.^[27]

Efficiency

• In vitro fertilization (IVF) generates large numbers of unused embryos (e.g. 70,000 in Australia alone).^[23] Many of these thousands of IVF embryos are slated for destruction. Using them for scientific research uses a resource that would otherwise be wasted.^[23]
• While the destruction of human embryos is required to establish a stem cell line, no new embryos have to be destroyed to work with existing stem cell lines. It would be wasteful not to continue to make use of these cell lines as a resource.^[23]

Superiority

This is usually presented as a counter-argument to using adult stem cells as an alternative that does not involve embryonic destruction.

• Embryonic stem cells make up a significant proportion of a developing embryo, while adult stem cells exist as minor populations within a mature individual (e.g. in every 1,000 cells of the bone marrow, only one will be a usable stem cell). Thus, embryonic stem cells are likely to be easier to isolate and grow ex vivo than adult stem cells.^[23]
• Embryonic stem cells divide more rapidly than adult stem cells, potentially making it easier to generate large numbers of cells for therapeutic means. In contrast, adult stem cell might not divide fast enough to offer immediate treatment.^[23]
• Embryonic stem cells have greater plasticity, potentially allowing them to treat a wider range of diseases.^[23]
• Adult stem cells from the patient's own body might not be effective in treatment of genetic disorders. Allogeneic embryonic stem cell transplantation (i.e. from a healthy donor) may be more practical in these cases than gene therapy of a patient's own cell.^[23]
• DNA abnormalities found in adult stem cells that are caused by toxins and sunlight may make them poorly suited for treatment.^[23]
• Embryonic stem cells have been shown to be effective in treating heart damage in mice.^[23]
• Embryonic stem cells have the potential to cure chronic and degenerative diseases which current medicine has been unable to effectively treat.

Individuality

• Before the primitive streak is formed when the embryo attaches to the uterus around 14 days after fertilization, two fertilized eggs can combine by fusing together and develop into one person (a tetragametic chimera). Since a fertilized egg has the potential to be two individuals or half of one, some believe it can only be considered a 'potential' person, not an actual one. Those who subscribe to this belief then hold that destroying a blastocyst for embryonic stem cells is ethical.^[28]

Viability

• Viability is another standard under which embryos and fetuses have been regarded as human lives. In the United States, the 1973 Supreme Court case of Roe v. Wade concluded that viability determined the permissibility of abortions performed for reasons other than the protection of the woman's health, defining viability as the point at which a fetus is "potentially able to live outside the mother's womb, albeit with artificial aid."^[29] The point of viability was 24 to 28 weeks when the case was decided and has since moved to about 22 weeks due to advancement in medical technology. Embryos used in medical research for stem cells are well below development that would enable viability.

Objection

Alternatives

This argument is used by opponents of embryonic destruction, as well as researchers specializing in adult stem cell research.

Pro-life supporters often claim that the use of adult stem cells from sources such as umbilical cord blood has consistently produced more promising results than the use of embryonic stem cells.^[30] Furthermore, adult stem cell research may be able to make greater advances if less money and resources were channeled into embryonic stem cell research.^[31]

In the past, it has been a necessity to research embryonic stem cells and in doing so destroy them for research to progress.^[32] As a result of the research done with both embryonic and adult stem cells, new techniques may make the necessity for embryonic cell research obsolete. Because many of the restrictions placed on stem cell research have been based on moral dilemmas surrounding the use of embryonic cells, there will likely be rapid advancement in the field as the techniques that created those issues are becoming less of a necessity.^[33] Many funding and research restrictions on embryonic cell research will not impact research on IPSCs (induced pluripotent stem cells) allowing for a promising portion of the field of research to continue relatively unhindered by the ethical issues of embryonic research.^[34]

Adult stem cells have provided many different therapies for illnesses such as Parkinson's disease, leukemia, multiple sclerosis, lupus, sickle-cell anemia, and heart damage^[35] (to date, embryonic stem cells have also been used in treatment),^[36] Moreover, there have been many advances in adult stem cell research, including a recent study where pluripotent adult stem cells were manufactured from differentiated fibroblast by the addition of specific transcription factors.^[37] Newly created stem cells were developed into an embryo and were integrated into newborn mouse tissues, analogous to the properties of embryonic stem cells.

Stated views of groups

Government policy stances

Europe

Austria, Denmark, France, Germany, and Ireland do not allow the production of embryonic stem cell lines,^[38] but the creation of embryonic stem cell lines is permitted in Finland, Greece, the Netherlands, Sweden, and the United Kingdom.^[38]

United States

Origins

In 1973, Roe v. Wade legalized abortion in the United States. Five years later, the first successful human in vitro fertilization resulted in the birth of Louise Brown in England. These developments prompted the federal government to create regulations barring the use of federal funds for research that experimented on human embryos. In 1995, the NIH Human Embryo Research Panel advised the administration of President Bill Clinton to permit federal funding for research on embryos left over from in vitro fertility treatments and also recommended federal funding of research on embryos specifically created for experimentation. In response to the panel's recommendations, the Clinton administration, citing moral and ethical concerns, declined to fund research on embryos created solely for research purposes,^[39] but did agree to fund research on leftover embryos created by in vitro fertility treatments. At this point, the Congress intervened and passed the Dickey Amendment in 1995 (the final bill, which included the Dickey Amendment, was signed into law by Bill Clinton) which prohibited any federal funding for the Department of Health and Human Services be used for research that resulted in the destruction of an embryo regardless of the source of that embryo.

In 1998, privately funded research led to the breakthrough discovery of human embryonic stem cells (hESC). This prompted the Clinton administration to re-examine guidelines for federal funding of embryonic research. In 1999, the president's National Bioethics Advisory Commission recommended that hESC harvested from embryos discarded after in vitro fertility treatments, but not from embryos created expressly for experimentation, be eligible for federal funding. Though embryo destruction had been inevitable in the process of harvesting hESC in the past (this is no longer the case^{[40][41][42][43]}), the Clinton administration had decided that it would be permissible under the Dickey Amendment to fund hESC research as long as such research did not itself directly cause the destruction of an embryo. Therefore, HHS issued its proposed regulation concerning hESC funding in 2001. Enactment of the new guidelines was delayed by the incoming George W. Bush administration which decided to reconsider the issue.

President Bush announced, on August 9, 2001, that federal funds, for the first time, would be made available for hESC research on currently existing embryonic stem cell lines. President Bush authorized research on existing human embryonic stem cell lines, not on human embryos under a specific, unrealistic timeline in which the stem cell lines must have been developed. However, the Bush Administration chose not to permit taxpayer funding for research on hESC cell lines not currently in existence, thus limiting federal funding to research in which "the life-and-death decision has already been made".^[44] The Bush Administration's guidelines differ from the Clinton Administration guidelines which did not distinguish between currently existing and not-yet-existing hESC. Both the Bush and Clinton guidelines agree that the federal government should not fund hESC research that directly destroys embryos.

Neither Congress nor any administration has ever prohibited private funding of embryonic research. Public and private funding of research on adult and cord blood stem cells is unrestricted.