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Tuesday, May 17, 2011

Human Cloning

Animal cloning has produced some remarkable results within the last few years, which has suggested to some that there should be a way to produce a human clone within the next year. Many news articles have appeared recently highlighting the potential to clone a human baby in order to replace a loved one who died as a newborn.

Many social, moral, and ethical arguments have been raised in opposition to copying a person. For more details see AMA's 1999 CEJA Report: The Ethics of Cloning (PDF, 41KB). But perhaps more important is the concern that we do not fully understand the science behind the successes from animal cloning experiments.

Animal cloning success (and failure)
Dolly, the sheep, was the first successfully cloned mammal (I. Wilmut et al., Nature 1997;385:810). Since 1997, gradual improvements in cloning technology have enabled researchers to generate mouse, cattle, goat, pig, deer, rabbit, cat, mule, and horse clones. While there have been no substantiated evidence for the cloning of humans, recent successes by South Korean researchers in generating stem cells from cloned human embryos (WS Hwang et al., Science 2005) have heightened concerns that this scenario is not beyond the realm of possibility.

In spite of recent technological advances, animal cloning remains extremely inefficient. For every 100 experiments only one, two, or if lucky, perhaps three appear to produce a viable offspring in surrogate mothers. While scientific explanations for these failures remain to be defined, many researchers feel they represent nothing more than technical hurdles that will one day be solved. Even then it's survival beyond the perinatal period is unlikely. These is no reason to believe that any different outcomes will occur if and when human cloning begins.

A quick lesson in cloning technology
Before going into the details of why these abnormalities are thought to occur, it is important to have a basic understanding of what in essence happens in order to clone an animal. First, a donor cell is found, which has its original DNA extracted and discarded. Next is the addition of a nucleus from the desired animal that is to be cloned. The third step involves implanting the combined cell into the animal that the donor cell was appropriated from.

Understanding the abnormalities
This part of the puzzle is as yet unsolved, but theories do point us in some tangible directions. Scientists believe that the resultant cloning abnormalities are not traceable to the donor nuclei, but more likely explanations involve failures in genomic reprogramming.

Genomic reprogramming in the natural way prior to embryogenesis (i.e., without cloning technology) involves a stage of development of the sperm and the egg known as gametogenesis, which can take months to years to develop a mature gamete. This process is sped up during cloning, and takes only minutes to hours. The process of configuring the exact state of the inner workings of the cell including such complex processes as methylation of the DNA may not be correct for the development of the embryo.

Methylation of DNA and other complex functions are now known to be essential to the correct functioning of each human cell, since they ultimately control gene expression. And thus successful cloning may be dependent upon the donated DNA being correctly altered to the state of an early embryo. It is thought by some cloning experts that failure of the nuclear clones to produce viable offspring is due to inappropriate reprogramming of cells, which leads to unregulated gene expression.

Screening tools, do they exist?
Because of experience with animal clones, it is reasonable to conclude that future human cloning experiments will have the same high failure rates. The public has heard reassurance that the possibility of performing prenatal genetic screening exists as a way to control quality. If these groups plan on using current routine prenatal diagnosis for the detection of chromosomal and/or other genetic abnormalities, they will not detect the types of epigenetic disturbances that may occur with cloning. There are no extra tools in the developmental pipeline to help improve detection.

Possible reaction to human cloning failures
Besides the public outrage that would accompany human cloning failures would in turn hinder science and genetics, research in areas such as embryonic stem cells for the repair of organs and tissues could be negatively impacted. Research is ongoing to develop reprogramming of certain cells to turn into specific tissues types, which could regenerate nerve, muscle, and other cell types, alleviating Parkinson's, Alzheimer's, and heart disease among other chronic illnesses. The potential benefits of therapeutic cell cloning are enormous, and this research should not be jeopardized with human cloning activities.

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