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Cloning: From DNA Molecules to Dolly

 
Author: Aaron Hall
The possibility of human cloning, raised when Scottish scientists at Roslin Institute created the much-celebrated sheep "Dolly" (Nature 385, 810-13, 1997), has aroused worldwide interest and concern because of its scientific and ethical implications. The feat, cited by Science magazine as the breakthrough of 1997, also has generated uncertainty over the meaning of "cloning" --an umbrella term traditionally used by scientists to describe different processes for duplicating biological material.

Cloning DNA, Cells, and Animals
To Human Genome Project researchers, cloning refers to copying genes and other pieces of chromosomes to generate enough identical material for further study. Cloned collections of DNA molecules (called clone libraries) enable scientists to produce increasingly detailed descriptions of all human DNA--the aim of the Human Genome Project. Bacterial or yeast cells are used routinely by scientists to make these extra copies of human DNA molecules. Researchers also can exploit the natural process of cell division to make many copies of an entire cell. The genetic makeup of these cloned cells, called a cell line, is identical to the original cell.

Two other types of cloning produce complete, genetically identical animals. Blastomere separation (sometimes called "twinning" after the naturally occurring process that creates identical twins_ involves splitting a developing embryo soon after fertilization of the egg by a sperm (sexual reproduction) to give rise to two or more embryos. The resulting organisms are identical twins (clones) containing DNA from both the mother and the father.

Dolly, on the other hand, is the result of another type of cloning that produces an animal carrying the DNA of only one parent. Using somatic cell nuclear transfer, scientists transferred genetic material from the nucleus of an adult sheep's udder cell to an egg whose nucleus, and thus its genetic material, had been removed. (All cells that are not egg or sperm cells are somatic cells.)

Why Clone?
One goal of this and similar research is to develop efficient ways to alter animals genetically and reproduce them reliably. Alterations have included adding genes (such as those for human proteins) to create drug-producing animals as well as inactivating genes to study the effects and possibly create animal models of human diseases. Cloning technology also may someday be used in humans to produce whole organs from single cells or to raise animals having genetically altered organs suitable for transplanting to humans.

The technique used to produce Dolly and other cloned animals is an extension of 40 years of research using DNA from nonhuman embryonic and fetal cells. Before this demonstration, scientists believed that once a cell became specialized'a liver, heart, udder, bone, or any other type of cell'the change was permanent and other unneeded genes in the cell became inactive. Dolly's creators demonstrated that nuclei of an adult animal's specialized cells can be made to revert to a nonspecialized, embryonic state, thus restoring the ability to give rise to any kind of cell. Explorations into how cells revert to an undifferentiated state may provide insights into the process by which cells become cancerous.

NBAC Recommendations
Following the birth of Dolly in 1997, public reaction prompted U.S. President Bill Clinton to ask the National Bioethics Advisory Commission (NBAC) for recommendations on the science of human cloning and its ethical, religious, legal, and regulatory implications. Released in June 1997, the NBAC report concluded that attempts to clone humans are 'morally unacceptable' for safety and ethical reasons. NBAC advised continuing the current moratorium on using federal funds for human cloning but recommended that any legislation should be temporary and that the situation should be reviewed again in 3 to 5 years. The NBAC report is available on the Web (http://www.bioethics.gov). In January 1998, the U.S. Food and Drug Administration (FDA) announced its authority to regulate human cloning, thus making it a violation of federal law for anyone to try the procedure without FDA approval. Acting FDA Commissioner Michael Friedman stated that the agency considers the manipulations involved in human cloning to be serious health and societal issues for the mother and fetus.

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