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

The sheep was originally code-named "6LL3". The name "Dolly" came from a suggestion by the stockmen who helped with her birth, in honor of Dolly Parton, because it was a mammary cell that was cloned^[1]. 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 center of much controversy that still exists today.

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

Dolly

Dolly and her first-born lamb, Bonnie

Dolly was created by a research team managed by Ian Wilmut at the Roslin Institute in Scotland. The goal of the research was the reliable reproduction of mammals genetically modified to produce therapeutic proteins in their milk. Wilmut's team had already created 2 sheep clones from embryonic cells grown in culture called Megan and Morag; the work was published in Nature in 1996^[2]. 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^[3]. Dolly was the first mammalian clone produced from an adult somatic cell.

Premature aging

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^[4]. It was speculated that these were passed on from her donor sibling, 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.

Possible signs of her condition 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."

Others speculate that Dolly's arthritis resulted from her lifestyle as a scientific curiosity and protected specimen due to a lack of normal outdoor exercise and unnatural stress on her joints.

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 in- and outside 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 can not 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

Dolly's remains as exhibited in the Royal Museum of Scotland

On February 15, 2003 it was announced that Dolly had died from a progressive lung disease. A necropsy confirmed she had Ovine Pulmonary Adenocarcinoma (Jaagsiekte), a fairly common disease of sheep caused by a retrovirus. 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 now 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, ergo 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 two 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.

Controversy

In March 2006 it was revealed that the scientists involved were in major disagreement over who deserves credit for Dolly. In 2006, while testifying at an Edinburgh court following accusations of racial harassment of his fellow Prim Singh, Ian Wilmut denied the accusations, but acknowledged that he was not the 'father' or 'creator' of Dolly, that he has minimised the role of some of his fellows, and he gave most of the credit (66 percent) to Keith Campbell, while playing a 'supervisory' or managerial role.

In January 2007, the FDA decided to permit the sale and consumption of meat and milk from cloned animals in the United States.

References

1. ^ BBC News. 2000. Listen to public, says Dolly scientist
2. ^ Campbell, K.H.S., McWhir, J., Ritchie, W.A. and Wilmut, A. (1996). "Sheep cloned by nuclear transfer from a cultured cell line". Nature 380 (6569): 64-66. PMID 8598906 DOI:10.1038/380064a0.
3. ^ Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J., Campbell, K.H.S. (1997). "Viable offspring derived from fetal and adult mammalian cells". Nature 385 (6619): 810-813. PMID 9039911 DOI:10.1038/385810a0.
4. ^ Shiels, P.G. et al. (1999). "Analysis of telomere lengths in cloned sheep". Nature 399 (6734): 316-317. PMID 10360570 DOI:10.1038/20580. BBC article

Wikipedia

http://en.wikipedia.org/w/index.php?title=Dolly_the_Sheep&action=history

http://www.gnu.org/copyleft/fdl.html