The idea that humans might someday be cloned created from a single somatic cell without sexual reproduction moved a step away from science fiction and closer to a genuine scientific possibility on February 23, 1997. On that date, the news broke that Ian Wilmut, a Scottish scientist, and his colleagues at the Roslin Institute were about to announce the successful cloning of a sheep by a new technique which had never before been fully successful in mammals. This technique involved transplanting the genetic material of an adult sheep, apparently obtained from a differentiated somatic cell, into an egg from which the nucleus had been removed. The resulting birth of the sheep, named Dolly, on July 5, 1996, was different from prior attempts to create identical offspring since Dolly contained the genetic material of only one parent, and was, therefore, a "delayed" genetic twin of a single adult sheep.Reproductive cloning is defined as the deliberate production of genetically identical individuals. Each newly produced individual is a clone of the original. Clones contain identical sets of genetic material in the nucleus—the compartment that contains the chromosomes—of every cell in their bodies. Therefore, cells from two clones have the same DNA and the same genes in their nuclei.
All cells, including eggs, also contain some DNA in the energy-generating “factories” called mitochondria. These structures are in the cytoplasm, the region of a cell outside the nucleus and this mitochondria contain their own DNA and reproduce independently.
HOW IS REPRODUCTIVE CLONING DONE?Two methods are used to make live-born mammalian clones. Both require implantation of an embryo in a uterus and then a normal period of gestation and birth.
The two methods used are as follows:
• Cloning using somatic cell nuclear transfer (SCNT) - This procedure starts with the removal of the chromosomes from an egg to create an enucleated egg. The chromosomes are replaced with a nucleus taken from a somatic (body) cell of the individual or embryo to be cloned. This cell could be obtained directly from the individual, from cells grown in culture, or from frozen tissue. The egg is then stimulated, and in some cases it starts to divide. If that happens, a series of sequential cell divisions leads to the formation of a blastocyst, or preimplantation embryo. This blastocyst is then transferred to the uterus of an animal. The successful implantation of the blastocyst in a uterus can result in its further development, culminating sometimes in the birth of an animal. This animal will be a clone of the individual that was the donor of the nucleus. Its nuclear DNA has been inherited from only one genetic parent.The number of times that a given individual can be cloned is limited theoretically only by the number of eggs that can be obtained to accept the somatic cell nuclei and the number of females available to receive developing embryos. If the egg used in this procedure is derived from the same individual that donates the transferred somatic nucleus, the result will be an embryo that receives all its genetic material—nuclear and mitochondrial—from a single individual. That will also be true if the egg comes from the nucleus donor’s mother, because mitochondria are inherited maternally. Multiple clones might also be produced by transferring identical nuclei to eggs from a single donor. If the somatic cell nucleus and the egg come from different individuals, they will not be identical to the nuclear donor because the clones will have somewhat different mitochondrial genes.
• Cloning by embryo splitting. This procedure begins with In Vitro Fertilization (IVF): the union outside the woman’s body of a sperm and an egg to generate a zygote. The zygote ( also called an embryo) divides into two and then four identical cells. At this stage, the cells can be separated and allowed to develop into separate but identical blastocysts, which can then be implanted in a uterus. The limited developmental potential of the cells means that the procedure cannot be repeated, so embryo splitting can yield only two identical mice and probably no more than four identical humans.The DNA in embryo splitting is contributed by germ cells from two individuals—the mother who contributed the egg and the father who contributed the sperm. Thus, the embryos, like those formed naturally or by standard IVF, have two parents. Their mitochondrial DNA is identical.
WILL CLONES LOOK AND BEHAVE EXACTLY THE SAME?Even if clones are genetically identical with one another, chances are they will not be identical in physical or behavioral characteristics, because DNA is not the only determinant of these characteristics. A pair of clones will experience different environments and nutritional inputs while in the uterus, and they would be expected to be subject to different inputs from their parents, society, and life experience as they grow up. If clones derived from identical nuclear donors and identical mitochondrial donors are born at different times, as is the case when an adult is the donor of the somatic cell nucleus, the environmental and nutritional differences would be expected to be more pronounced than for monozygotic (identical) twins. And even monozygotic twins are not fully identical genetically or epigenetically because mutations, stochastic developmental variations, and varied imprinting effects (parent-specific chemical marks on the DNA) make different contributions to each twin.
Additional differences may occur in clones that do not have identical mitochondria. Such clones arise if one individual contributes the nucleus and another the egg—or if nuclei from a single individual are transferred to eggs from multiple donors. The differences might be expected to show up in parts of the body that have high demands for energy—such as muscle, heart, eye, and brain—or in body systems that use mitochondrial control over cell death to determine cell numbers.
Cloning is done for various reasons some of which include:
- Infertile couples who wish to have a child that is genetically identical with one of them, or with another nucleus donor
- Other individuals who wish to have a child that is genetically identical with them, or with another nucleus donor
- Parents who have lost a child and wish to have another, genetically identical child
- People who need a transplant (for example, of cord blood) to treat their own or their child’s disease and who therefore wish to collect genetically identical tissue from a cloned fetus or newborn.
Defects of cloningA wide array of abnormalities and defects (including the differences stated above) have been observed in reproductively cloned animals, both before and after birth. However, these abnormalities have not always been studied in detail, possibly because most reproductive animal cloning has been done for commercial purposes and there is less interest in the failures than in the successes.
The most notable defects are increased birth size, placental defects, lung, kidney, cardiovascular problems, liver, joint, and brain defects, immune dysfunction, and postnatal weight gain. Thus, a wide variety of tissues and organs can fail to develop properly in cloned animals, and some of the reported defects (such as aberrant growth and development of lung tissue and the immune system) cannot be diagnosed or prevented with current technology, such as prenatal screening with ultrasonography.
Many of the defects seen in cloned cattle and sheep (for example, high birth weight, abnormal placentation, fluid accumulation associated with maternal and fetal distress, and cardiovascular abnormalities) are the same as those described for “large offspring syndrome” (LOS). This is frequently seen in uncloned offspring produced after in vitro fertilization and embryo manipulation in these species (but not in others, including humans) and is attributed to, among other things, the exposure of eggs and embryos to suboptimal culture conditions in the laboratory.
Animal cloning can also result in danger to the mother of any cloned offspring. Increased maternal morbidity and mortality can result from late gestational fetal loss, increased size of the fetus, abnormal placentation, pregnancy toxemia, and, most notably, hydrallantois and/or hydramnios (excessive fluid accumulation in the uterus often associated with fetal abnormality and maternal distress). These effects have been seen most prominently in studies with cattle and sheep, example, in the cattle cloning study, four of the 13 pregnant cows and their fetuses died because of complications late in pregnancy.
In conclusion, if results from animal reproductive cloning studies are compared to humans, they suggest that reproductive cloning of humans could carry a very high risk to the health of both fetus or infant and mother and lead to associated psychological risks for the parents as a consequence of late spontaneous abortions or the birth of a stillborn child. Moreover, if the cloned human fetus or placenta grew abnormally large, this could cause problems before a cesarean section would be an option, particularly if multiple embryos are placed in the uterus, which is the procedure in most IVF clinics in the United States.Since the effects of cloning actually outweigh the benefits, do you think human or even animal cloning is worth taking the risk for? More research and tests are ongoing to curb its defects and we expect probably good results in a few decades or less.
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