Dolly the sheep

Dolly (5 July 1996 – 14 February 2003), a ewe, was the first mammal to have been successfully cloned from an adult cell. She was cloned at the Roslin Institute in Scotland and lived there until her death when she was 6. Her birth was announced on 22 February 1997.

The sheep was originally code-named "6LL3". The name "Dolly" came from a suggestion by the stockmen who helped with her birth, in honour of Dolly Parton, because it was a mammary cell that was cloned. The technique that was made famous by her birth is somatic cell nuclear transfer, in which a cell is placed in a de-nucleated ovum, the two cells fuse and then develop into an embryo. When Dolly was cloned in 1996 from a cell taken from a six-year-old ewe, she became the centre of much controversy that still exists today.

On 9 April 2003 her stuffed remains were placed at Edinburgh's Royal Museum, part of the National Museums of Scotland.


Creating Dolly

Dolly was created by a research team lead by Ian Wilmut at the Roslin Institute in Scotland. The goal of the research was the reliable reproduction of animals genetically modified to produce therapeutic proteins in their milk. Wilmut's team had already created two sheep clones from embryonic cells grown in culture called Megan and Morag, the work was published in Nature in 1996. Dolly was a Finn Dorset lamb, created from fully differentiated adult mammary cells using a technique called somatic cell nuclear transfer, her creation was described in a Nature publication in 1997. Dolly was the first mammalian clone produced from an adult cell. She was produced by the process of somatic cell nuclear transfer.


Controversy

In 1999 research was published in the journal Nature suggesting that Dolly may have been susceptible to premature aging, due to shortened telomeres in her cells. It was speculated that these were passed on from her parent, who was six years old when the genetic material was taken from her, so that Dolly may have been genetically six years old at birth. This is because telomere length is reduced after each cell division, which requires DNA replication before mitosis occurs. The polymerase, part of the replication machinery, cannot reach the end of the chromosome being replicated and clips a little of the telomere at the end off every time replication occurs. However, Dr. John Thomas indicated that most cloned animals actually have telomeres of normal length and in serial clones the telomeres are actually getting longer in each successive generation. This is because the enzyme telomerase is active in those clones, which keeps the telomeres from shortening. However, telomerase, which is present in many bacteria, can be responsible for causing mutation through its enzymatic activity, which leads to cancer. In fact, many human cancer cells produce telomerase in the course of carcinogenesis, which is not normally present in most adult human cells.

Possible signs of this were reported in January 2002, when Dolly was five years old. She had developed a potentially debilitating form of arthritis at an unusually early age. This supported the theory of premature senescence, although Dr. Dai Grove-White of the Faculty of Veterinary Science at Liverpool University was reported as saying, "Conceivably arthritis could be due to the cloning but equally it could not be. For all we know, she may have damaged her leg jumping over a gate and developed arthritis."

The arthritis further fueled worry among some that this form of cloning may not be appropriate for mammals, and there is now a consensus both within and outside the scientific community that at this point the risk of unforeseen effects of cloning on the clone makes experiments in human reproductive cloning premature and unethical.

Supporters of this method of cloning counter that the technique used to clone Dolly simply needs to be refined. However, others contend that with very limited understanding of the nascent field of applied genetics, scientists cannot, and should not, attempt to control the action of so many genes at once. Many outside the scientific community have stated that this is vindication for their initial assertions that any form of cloning is ethically wrong and should be banned.


Death

On February 14, 2003 it was announced that Dolly had a progressive lung disease. A necropsy confirmed she had sheep pulmonary adenomatosis, a fairly common disease of sheep. Roslin scientists stated that they did not think there was a connection with Dolly being a clone, and that other sheep on the farm had similar ailments. Such lung diseases are especially a danger for sheep kept indoors, as Dolly had to be for security reasons.


Legacy

After the cloning was successfully demonstrated by Dolly's creators, many other large mammals have been cloned, including horses and bulls. Cloning is sometimes considered a promising tool for preserving endangered species, usually by those who do not work in species conservation. Most animal conservation professionals point out that cloning does not alleviate the problems of loss of genetic diversity (see inbreeding) and habitat, must be considered an experimental technology for the time being, and all in all would only rarely be worth the cost, which on a per-individual basis far exceeds conventional techniques such as captive breeding or embryo transfer. The 2000-2001 attempt to clone a gaur failed, with the animal, "Noah", dying 2 days after birth, and the attempt to clone argali sheep did not produce viable embryos. The attempt to clone a banteng bull was more successful, as were the attempts to clone mouflon, both resulting in viable offspring. The banteng example is a case illustrating the circumstances under which the uncertainties of cloning attempts are outweighed by the benefits: the cell donator was an adult of a rare genotype combination which had been killed in a fight; the single surviving cloned individual now is integrated into the herd at San Diego Zoo and healthy (it had to undergo orchiopexy, but this was probably due to an inbreeding and not a cloning problem).

There have been some attempts and many suggestions to clone extinct animals, but those that have seen any research (thylacine, huia, Pyrenean Ibex and mammut) have so far resulted in failures. Altogether, the only real benefit of cloning for animal conservation exists in some cases of large mammals where embryo transfer techniques are already established and the issue at hand is preservation of a rare genetic lineage, as in the case of the San Diego banteng.