Advocates of therapeutic cloning point to other treatment benefits such as using stem cells to generate bone marrow for transplants. They contend that scientists could use therapeutic cloning to manufacture perfectly matched bone marrow using the patient's own skin or other cells. This would eliminate the problem of rejection of foreign tissue associated with bone marrow transplant and other organ transplantation. Stem cells also have the potential to repair and restore damaged heart and nerve tissue. Further, there is mounting evidence to suggest that stem cells from cloned embryos have greater potential as medical treatments than stem cells harvested from unused embryos at fertility clinics, which are created by in vitro fertilization and are now the major source of stem cells for research. These prospective benefits are among the most compelling arguments in favor of cloning to obtain embryonic stem cells.
Stem cells used in research are harvested from the blastocyst after it has divided for five days, during the earliest stage of embryonic development. Harvesting stem cells does, however, destroy the embryo. Many people regard human embryos as human beings or at least potential human beings and consider their destruction to be immoral or unethical.
In November 2001 ACT researchers announced that they had created a cloned human embryo, and, unlike groups that had claimed to have done this before, the ACT team published its results (Jose B. Cibelli et al., "Somatic Cell Nuclear Transfer in Humans: Pronuclear and Early Embryonic Development," e-biomed: The Journal of Regenerative Medicine, vol. 2, November 25, 2001). The biotechnology firm's press release boasted that this achievement offered "the first proof that reprogrammed human cells can supply tissue" and asserted that this accomplishment was a vital first step toward the objective of therapeutic cloning—using cloned embryos to harvest embryonic stem cells able to grow into replacement tissue perfectly matched to individual patients. To clone the human embryos, investigators collected women's eggs and painstakingly removed the genetic material from the eggs with a thin needle. A skin cell was inserted inside each of eight enucleated eggs, which were then chemically stimulated to divide. Just three of the eight eggs began dividing, and only one reached six cells before cell division ceased.
The same year investigators at the South Australian Research and Development Institute used lambs to experiment with therapeutic cloning. The goal was to replace cells stricken with Parkinson's disease with healthy ones derived from a cloned embryo. In 2003 researchers in Italy reported successfully using adult stem cells to cure mice that had a form of multiple sclerosis. The scientists injected the diseased mice with stem cells that had been extracted from the brains of adult mice reproduced in the laboratory. Postmortem examination of the mice showed that the stem cells had migrated to and then repaired damaged areas of the nerves and brain.
In August 2003 a Chinese research team led by Huizhen Sheng, an American-trained scientist working at the Shanghai Second Medical University, reported that it had made human embryonic stem cells by combining human skin cells with rabbit eggs. Their accomplishment was published in the Chinese scientific journal Cell Research, a peer-reviewed publication of the Shanghai Institute of Cell Biology and the Chinese Academy of Sciences. The researchers removed the rabbit eggs' DNA and injected human skin cells inside them. The eggs then grew to form embryos containing human genetic material. After several days the embryos were dissected to extract their stem cells.
In February 2004 scientists at Seoul National University in Korea reported in the journal Science that they had successfully cloned healthy human embryos, removed embryonic stem cells, and grown them in mice. Scientists in England sought permission from their government to perform similar research, and a team of Harvard scientists sought and obtained permission from their university's ethics board to create cloned human embryos for medical research.
In February 2005 Professor Ian Wilmut, who had cloned Dolly the sheep, was granted a license by the British government to clone human embryos to generate stem-cell lines to study motor neuron disease (MND). Wilmut and his colleagues planned to clone embryos to generate stem cells that would in turn become motor neurons with MND-causing gene defects. By observing the stem cells grow into neurons, the researchers hoped to discover what causes the cells to degenerate. They planned to compare the stem cells with healthy and diseased cells from MND patients to gain a better understanding of the illness and to test potential drug treatments.
Human reproductive cloning remains illegal in Britain but therapeutic cloning—creating embryos as a source of stem cells to cure diseases—is allowed on an approved basis. The license granted to Wilmut and his colleagues is the second one granted by Britain's Human Fertilisation and Embryology Authority.
On March 14, 2005, Dr. Wilmut was awarded Germany's most prestigious medical award—the Paul Ehrlich and Ludwig Darmstaedter Prize—despite opposition from some members of the German Finance Ministry, which partly funds the award. In response, Wilmut vowed to spend the $134,000 (U.S.) prize on projects to help patients suffering from ailments such as Parkinson's disease (Angelika Brecht-Levy, "Dolly the Sheep's Creator Gets Award," Associated Press, March 14, 2005).
In 2004 Hans S. Keirstead, an assistant professor at the University of California at Irvine, used human embryonic stem cells to enable paralyzed rats to walk. He intended to begin clinical trials of this therapy to treat people with recent spinal cord injuries in 2005. Dr. Keirstead campaigned alongside the late Christopher Reeve, the paralyzed actor who championed stem cell therapy, to encourage Californians to vote to approve Proposition 71, a ballot measure allocating $3 billion of the state's money to embryonic stem cell research over the next decade. The measure passed in November 2004, and in 2005 plans were underway to distribute the funds.
Research Promises Therapeutic Benefits without Cloning
In "Homologous Recombination in Human Embryonic Stem Cells" (Nature Biotechnology, vol. 21, no. 3, February 2003), Thomas Zwaka and James Thomson reported that they had used human embryonic stem cells to splice out individual genes and substituted different genes in their place. Zwaka and Thomson's accomplishment was heralded as a first step toward the goal of regenerating parts of the human body by transplanting either stem cells or tissues grown from stem cells into patients. The researchers used electrical charges and chemicals to make the cells' membranes permeable; the cells allowed the customized genes to enter, and they then found and replaced their counterparts in the cells' DNA.
The ability to make precise genetic changes in human stem cells could be used to boost their therapeutic potential or make them more compatible with patients' immune systems. Some researchers assert that the success of this bioengineering feat might eliminate the need to pursue the hotly debated practice of therapeutic cloning, but others caution that such research could heighten concerns among those who fear that stem cell technology will lead to the creation of "designer babies," bred for specific characteristics such as appearance, intelligence, or athletic prowess.
In May 2003 University of Pennsylvania researchers Hans Schoeler and Karin Huebner reported another historic first: They transformed ordinary mouse embryo cells into egg cells in laboratory dishes (ScienceDaily, May 2, 2003). Schoeler and Huebner selected from a population of stem cells the ones that bore certain genetic traits suggesting the potential to become eggs. They then isolated those in laboratory dishes. After a while, the cells morphed into two kinds of cells, including young egg cells. The eggs matured normally and appeared to be healthy in terms of their appearance, size, and gene expression. When cultured for a few days, the eggs also underwent spontaneous division and formed structures resembling embryos, a process called parthenogenesis. This finding implies that the eggs were fully functional and likely can be fertilized with sperm.
Once refined, this technology could be applied to produce egg cells in the laboratory that would enable scientists to engineer traits into animals and help conservationists rebuild populations of endangered species. It offers researchers the chance to observe mammalian egg cells as they mature, a process that occurs unseen within the ovary. The technology also offers an unparalleled opportunity to learn about meiosis (reduction division), the process of cell division during which an egg or sperm disgorges half of its genes so it can join with a gamete of the opposite sex. There are many potential medical benefits as well. For example, women who cannot make healthy eggs could use this technology to ensure healthy offspring.
Like many new technologies, transforming cells into eggs simultaneously resolves existing ethical issues and creates new ones. For example, since the embryonic stem cells spontaneously transformed themselves into eggs, this procedure overcomes many of the ethical objections to cloning, which involves creating offspring from a single parent. On the other hand, it paves the way for the creation of "designer eggs" from scratch and, if performed with human cells, could redefine the biological definitions of mothers and fathers.
In September 2003 efforts to transform stem cells into sperm were successful. Toshiaki Noce and his colleagues in Tokyo observed male mouse embryonic stem cells that developed spontaneously, with some cells actually becoming germ cells. When the researchers transplanted the germ cells into testicular tissue, the cells underwent meiosis and formed sperm cells. One possible medical application of this technology would be to assist couples who are infertile because the male cannot produce healthy sperm. One of the ethical issues that might arise would be the potential for two men to both be biological fathers of a child. Another is the potential to generate a human being who never had any parents using two laboratory-grown stem cells, one transformed into a sperm and the other into an egg. Many ethicists advise consideration of such issues before permitting human experimentation.
In November 2004 researchers from the University of Pennsylvania School of Veterinary Medicine used cells from mice to grow sperm progenitor cells in a laboratory culture. Known as spermatogonial stem cells, the progenitor cells are incapable of fertilizing egg cells but give rise to cells that develop into sperm. The researchers transplanted the cells into infertile mice, which were then able to produce sperm and father offspring that were genetically related to the donor mice.
This breakthrough has many potential applications, including developing new treatments for male infertility and extending the reproductive lives of endangered species. Researchers also will attempt to genetically manipulate the sperm cells grown in a culture medium and then implant the cells into animals. In this way they could introduce new traits into laboratory animals and livestock, such as disease resistance. The culture technique offers researchers additional opportunities to investigate the potential of spermatogonial stem cells as a source for adult stem cells to replace diseased or injured tissue.
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