The stem cell controversy concerns the ethics of research involving the development and use of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves human embryos. For example, adult stem cells, amniotic stem cells, and induced pluripotent stem cells do not involve creating, using, or destroying human embryos, and 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. This significant discovery led to the first human bone marrow transplant by E. Donnall Thomas in 1956, 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 embryonic 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, allowing for a revival of research on human disease. In 1995 adult stem cell research with human use was patented (US PTO with effect from 1995). In fact, human use was published in World J Surg 1991 & 1999 (B G Matapurkar). Salhan, Sudha (August 2011).Textbook of Gynecology. JP Medical Ltd. pp. 625–. . Bharadwaj, Aditya; Glasner, Peter E. (2009). Local Cells, Global Science: The Rise of Embryonic Stem Cell Research in India. Taylor & Francis. "Dr.B.G.Matapurkar gets US patent for surgical procedure for organ regeneration - Patents". www.pharmabiz.com. ^ "Method of organogenesis and tissue regeneration/repair using surgical techniques – US Patent 6227202 Claims". patentstorm.us.
In 1998, James Thomson and Jeffrey Jones derived the first human embryonic stem cells, which had 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 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."Stem Cells for Tissue Regeneration and Joint Repair", Science Daily, 29 March 2006.
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. 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
Destruction of a human embryo is required in order to research new embryonic cell lines. Much of the debate surrounding human embryonic stem cells, therefore, concern ethical and legal quandaries around the destruction of an embryo. Ethical and legal questions such as "At what point does one consider life to begin?" and "Is it just to destroy a human embryo if it has the potential to cure countless numbers of patients and further our understanding of disease?" are central to the controversy. Political leaders debate how to regulate and fund research studies that involve the techniques used to remove the embryo cells. No clear consensus has emerged.
Much of the criticism stems from religious moral code, and, in the most high-profile case, US President George W Bush signed an executive order banning the use of federal funding for any stem 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." 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."
Alternatives to embryonic stem cells
Some stem cell researchers are working to develop techniques of isolating stem cells with similar potency as embryonic stem cells, but do not require the destruction of a human embryo.
Induced pluripotent stem cells (iPSCs) Foremost among these was the discovery in August 2006 that human adult somatic cells can be cultured in vitro with the four “Yamanaka factors” (Oct-4, SOX2, c-Myc, KLF4) which effectively returns a cell to the pluripotent state similar to that observed in embryonic stem cells. This major breakthrough won a Nobel Prize for the discoverers, Shinya Yamanaka and John Gurdon. Induced pluripotent stem cells are those derived from adult somatic cells and have the potential to provide an alternative for stem cell research that does not require the destruction of human embryos. Some debate remains about the similarities of these cells to embryonic stem cells as research has shown that the induced pluripotent cells may have a different epigenetic memory or modifications to the genome than embryonic stem cells depending on the tissue of origin and donor the iPSCs come from. While this may be the case, epigenetic manipulation of the cells is possible using small molecules and more importantly, iPSCs from multiple tissues of origin have been shown to give rise to a viable organism similar to the way ESCs can. This allows iPSCs to serve as a powerful tool for tissue generation, drug screening, disease modeling, and personalized medicine that has far fewer ethical considerations than embryonic stem cells that would otherwise serve the same purpose.
Somatic cell nuclear transfer (SCNT) 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. This technique known as somatic cell nuclear transfer (SCNT) creates pluripotent cells that are genetically identical to the donor. While the creation of stem cells via SCNT does not destroy an embryo, it requires an oocyte from a donor which opens the door to a whole new set of ethical considerations such as the debate as to whether or not it is appropriate to offer financial incentives to female donors.
Single-Cell blastomere biopsy 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. At the 2007 meeting of the International Society for Stem Cell Research (ISSCR), 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.ScienceNOW – Reuters: U.S. Company Says Grows Embryo-Safe Stem Cells
Amniotic fluid stem cells (AFSCs) 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." AFSCs have been found to express both embryonic and adult stem cell markers as well as having the ability to be maintained over 250 population doublings.
Umbilical cord blood (UCB) Similarly, pro-life supporters claim that the use of adult stem cells from sources such as the cord blood has consistently produced more promising results than the use of embryonic stem cells.Prentice, David. (October 17, 2005) "Live Patients & Dead Mice". Christianity Today. Retrieved on August 24, 2006. Research has shown that umbilical cord blood (UCB) is in fact a viable source for stem cells and their progenitors which occur in high frequencies within the fluid. Furthermore, these cells may hold an advantage over induced PSC as they can create large quantities of homogenous cells.
IPSCs and other embryonic stem cell alternatives must still be collected and maintained with the informed consent of the donor as a donor's genetic information is still within the cells and by the definition of pluripotency, each alternative cell type has the potential to give rise to viable organisms. Generation of viable offspring using iPSCs has been shown in mouse models through tetraploid complementation. This potential for the generation of viable organisms and the fact that iPSC cells contain the DNA of donors require that they be handled along the ethical guidelines laid out by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and International Society for Stem Cell Research (ISSCR).
Viewpoints Stem cell debates have motivated and reinvigorated the anti-abortion movement, whose members are concerned with the rights and status of the human embryo as an early-aged human life. They believe that embryonic stem cell research profits from and violates the sanctity of life and is tantamount to murder."The stated reason for President Bush's objection to embryonic stem cell research is that 'murder is wrong'" (BBC) 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 person.