September 2000
The mule Idaho Gem (born May 4, 2003) was the first clone born in the horse family. Source: University of Idaho.
Ever since the announcement of the birth of Dolly three years ago, additional sheep, cows, goats, pigs and mice have been cloned. The desire to produce farm animals with outstanding and useful characteristics is ancient. One of the reasons that cloning is attractive is that it reduces the effort and time needed for farmers to do what they have been doing for years: selecting and propagating the best of the herd. Success with the technique, however, has not been easy in these animals (less than 2% efficiency) and barely achievable in other species such as chickens, monkeys and dogs.
The science behind the cloning
The significance of the first cloned mammal, Dolly, was that for the first time cloning was achieved from an adult (differentiated) cell. To fully appreciate this point consider that normally, one cell, the fertilized egg, contains all of the information needed to multiply and give rise to all of the specialized cells in the body. It is important to remember that every cell in your body contains an identical set of genes. Cells turn on and off different genes as they become specialized (differentiated). For example, blood cells need the haemoglobin gene on while skins cells do not. In cloning, we are requiring that a differentiated cell (e.g. udder cell) reprograms or resets its genetic information so that it acts as a fertilized egg. Indeed, DNA-testing confirmed that Dolly originated from a differentiated udder cell. The technique used, nuclear transfer, involves removing the nucleus from an egg cell and replacing it with the nucleus from a differentiated cell. Although this procedure had been attempted for decades, Dr. Ian Wilmut and colleagues at the Roslin Institute in Scotland were able to create conditions that allowed the adult cell nucleus to reprogram its DNA, enabling their success with Dolly.
Dolly was the first mammal to have been successfully cloned from an adult cell in 1996. Source: Wikimedia Commons.
Therefore Dolly answered a major biological question “Does the DNA of a cell become irreversibly modified as the cell becomes specialized and differentiates?” with a clear NO. The DNA of a cell that has developed to fulfill a specific function clearly can be reprogrammed to direct the development of a new individual. New questions of basic science are being posed: “How does the reprogramming occur?”, “What genes are involved in the control of this event?”, and “Can all adult cells be cloned?” (some evidence suggests not).
There are still obvious problems as evidenced from the numerous deaths of cloned animals that occur just before or after birth. The problems may be due to the experimental conditions under which the eggs are handled or may be an inherent problem that arises because these animals only have one parent. Normally, half the chromosomes of the new individual come from a sperm cell and half from an unfertilized egg but in a clone all of the genetic material (except mitochondrial DNA) comes from the donor nucleus.
What lies ahead
Cloning is a big first step. Genetic manipulation of cloned animals is the future direction of the cloning frontier. It is here that concerns are loudly voiced and take up headlines in the media. The public and the media’s views on the future of cloning often ignore some of its potential benefits:
Agriculture and Drug Production: Not only can the best traits be perpetuated but farm animals could also be used as “machines” for large-scale production of medically important proteins. Polly, a transgenic cloned lamb, is an example. She is able to produce milk containing factor IX — the protein that is deficient in haemophiliacs.
Maintaining Biodiversity: Cloning may be an important tool for preserving endangered species if currently practiced methods fail.
Biomedical Research: Cloning can produce genetically identical laboratory animals which can be used as models for human disease. The most commonly used laboratory animal, the mouse, reproduces rapidly and its genetics have been well studied. Mice have been successfully cloned and will likely facilitate the discovery of new treatments for disease. Jean-Paul Renard, of the National Institute of Agricultural Research in France, is attempting to produce cloned transgenic rabbits to study cardiovascular disease in the hope of finding new treatments. In addition, it provides a model for studying the interaction of nuclear verses mitochondrial genes and for nuclear verses cytoplasmic factors.
Commercial Endeavours: Noting that no live dog clones have yet been reported, the company PerPETuate, Inc. (Connecticut) is freezing tissue from family pets for the future. Researchers have had little success in the steps required to make a dog clone, such as development after nuclear transfer and embryo implantation into the womb.
Treatment for Human Disease: Cells could be harvested from early embryos to provide cell and tissue replacement without the hazards of transplantation rejection. The U.K. government has recently accepted recommendations from its chief medical to permit research using embryos subject to controls, which include a 14-day limit (see the Department of Health website listed below in “learn more”).
To clone or not to clone humans
The cloning of human embryos for reproductive purposes is illegal at this time. Yet it is still important to examine the consequences and the likelihood of this scenario. The media may dream up and forecast robotic cloned armies of Hitler; however, identical twins illustrate that being genetically identical does not remove their humanness. Identical twins exhibit different personalities and behaviour because environment also plays a major role on who we become.
At any rate, there have been significant difficulties with cloning primates, including an extremely low success rate and a high number of abnormalities. These results make it unacceptable to attempt human cloning at this moment in time. The ethical and social issues that will arise in the future when more efficient methods are developed leave some time for a resolution. Some of the same issues that arose from in vitro fertilization will be revisited (e.g., infertile couples, “replacing” the death of an infant).
Conclusion
Cloning has opened many doors that could lead to remarkable medical advancements but, as with all new technologies, it will be accompanied by ethical and social dilemmas. Today’s successes will pave the road to improving efficiencies and help add to the basic understanding of our cells. Even Dolly’s creator, Ian Wilmut, is focusing less on sheep and more on understanding the mechanism of reprogramming our genetic material!
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