Somatic cell nuclear transfer
Somatic cell nuclear transfer (SCNT) is a reproductive technology that involves transferring the nucleus from a somatic cell—any non-reproductive cell in the body—into an egg cell whose nucleus has been removed. This technique is notable for its potential applications, including animal cloning, therapeutic cloning for medical purposes, and the generation of human embryonic stem cells for research. The SCNT process begins with enucleation of the egg cell, followed by the insertion of the somatic cell nucleus, which contains the necessary genetic material. The resulting fertilized egg behaves like a typical embryo, dividing and developing into cells that carry the DNA of the donor organism.
The historical development of SCNT began with early experiments in the 20th century and culminated in the successful cloning of Dolly the sheep in 1997. This breakthrough demonstrated the viability of using adult somatic cells for cloning, raising both scientific excitement and ethical concerns regarding the implications of such technology, particularly in relation to human cloning. While SCNT has potential benefits in treating various medical conditions and creating personalized tissues for transplants, it also faces scrutiny over the ethical considerations involving embryo use and the ramifications of cloning. Overall, SCNT continues to be a field of active research, balancing scientific innovation with moral and ethical questions.
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Subject Terms
Somatic cell nuclear transfer
Somatic cell nuclear transfer (SCNT), or just simply nuclear transfer, is a method of creating an embryo by inserting a nucleus from a donor cell into an egg cell. This process has a variety of potential uses, including cloning animals, therapeutic cloning for medicinal purposes, and to acquire human embryonic stem cells for research. SCNT involves removing the nucleus of an egg cell (a process called enucleation) and replacing it with a somatic cell's nucleus. A somatic cell is any cell in the body that is not reproductive in origin. Reproductive cells include sperm and egg cells. Examples of somatic cells include those found in the skin, organs, or nerves of human beings. All somatic cells have two sets of chromosomes, making them viable donor cells.
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The nucleus is the part of the cell that contains all of the genetic codes necessary to create new cells. Once fertilized in this manner, the egg cell acts as any other fertilized egg cell would by forming cells through mitosis that are copies of the original cell. The resulting cells contain DNA (deoxyribonucleic acid) that is virtually the same as that of the original organism that provided the donor nucleus.
Brief History
The origins of SCNT date back to 1938, when German scientist Hans Spemann speculated in his book Embryonic Development and Induction that it was possible to transfer a nucleus from a differentiated cell (that is, one that has been changed from one form of cell into another) into an egg after the egg's nucleus was removed. Despite his foresight, the technology to test his ideas did not exist until over a decade later.
In 1952, American researchers Robert King and Thomas Briggs developed a method for transferring nucleic material by using a small glass needle to remove the nucleus from an embryonic frog cell. While the embryos created by King and Briggs remained viable, subsequent efforts on other species of animals failed to produce surviving embryos. Further experiments by Derek Bromhall in England suggested this lack of viability might have been due to the comparatively crude methods used to pierce cell membranes when extracting the nucleus. Experiments to perform early forms of SCNT on species larger than mice also failed to show any promising advances.
By 1984, almost fifty years after Spemann produced his hypothesis about nuclear transfer, Danish scientist Steen Willadsen created the first cloned sheep embryos using this method. Willadsen discovered that by charging the cells with an electrical current after the nuclear transfer, the cells were more likely to remain viable. Although the cells resulted in viable embryos that could be placed into the uteruses of adult sheep, they did not develop into living organisms.
In 1996, Keith Campbell, Jim McWhir, William Ritchie, and Ian Wilmut of the Roslin Institute in Scotland were able to use nuclear transfer techniques to clone sheep embryos. The difference in their technique came during a stage of embryonic development called quiescence. During this period, it is believed that the cell moves into a state of suspended development similar to hibernation. By forcing the donor cell's nucleus into this state before transferring it into the host egg, these scientists were able to create viable embryos that sometimes became viable fetuses. This was achieved by depriving cells of a set of proteins known as growth factors. In 1997, they found that adult somatic cells worked as well as the pre-embryonic cells called blastocysts that had been used in previous experiments with nuclear transfer. Using these cells and the newly developed SCNT process, they were able to successfully create a cloned sheep they named Dolly.
Roslin Institute researchers realized that this process had other potential applications. As the somatic cells being used were not exposed to growth factors, the DNA remained unaltered. This enabled them to make their own deliberate modifications to the DNA during the quiescence stage. Using this methodology, they cloned a second sheep named Polly, who had human proteins in her DNA.
While these discoveries were hailed for their potential value in a number of medical and scientific arenas, some bioethicists worried that these advances could be used for potentially ambiguous purposes that had possible moral, legal, and ethical implications. Chief among their concerns was the possibility of cloning human beings; however, the later utilization of SCNT practices in stem cell research courted similar levels of controversy due to the destruction of a human embryo required by the process.
In 2011, scientists at the New York Stem Cell Foundation developed a transfer method in which the donor nucleus is inserted into an egg that is allowed to retain its own nucleus. This causes the cell to enter into the blastocyst stage, at which point stem cells are extracted. This new cell contains sixty-nine chromosomes rather than the forty-six found in a genetically healthy human. This is because the new cell contains both twenty-three chromosomes from the host egg and forty-six from the donor cell nucleus. As a result of these excess chromosomes, the cell is incapable of ever developing into a viable fetus.
Further experiments have developed processes that they believe may allow scientists to create embryonic stem cells that do not have an excess number of chromosomes. This could result in the creation of stem cell lines that can be used in therapeutic cloning. Scientists have found that using fetal cells as the source of the donor cells raises the likelihood that resulting SCNT processes will be successful.
Overview
While SCNT technology is recognized as having valuable applications, the ethical and moral considerations regarding its potential implications remain a scientific minefield. The primary concerns are related to the possible misuse of SCNT for human cloning and the use of fetal cells for stem cell research. For instance, SCNT could have possible applications in infertility treatments. However, the Ethics Committee of the American Society for Reproductive Medicine maintains that such use would be unethical due to lingering worries about safety and the emotional and health effects of such treatments, particularly when other methods of fertility treatments remain viable.
Similarly, stem cell research has lingering opposition from some quarters of the public due to the involvement of potentially viable human embryos. Stem cell research using SCNT could be used in therapeutic cloning, in which healthy tissues are created and replanted into people suffering from diseases or debilitating genetic conditions. Ideally, SCNT could be used someday to create organs or tissues created from the patient's own somatic cells that could be used in organ transplants or to help replace damaged tissues. SCNT treatments could also theoretically help patients with diabetes or Parkinson's disease.
Bibliography
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