Dolly (sheep)

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Dolly's remains are exhibited at the Royal Museum of Scotland.
Dolly's remains are exhibited at the Royal Museum of Scotland.

The ewe Dolly (July 5, 1996February 14, 2003) was the first animal to be cloned from an adult somatic cell, using the process of nuclear transfer.[1][2] She was cloned by Ian Wilmut, Keith Campbell and colleagues at the Roslin Institute in Edinburgh, Scotland. Her birth was announced on February 22, 1997 and she lived until the age of six.[3]

The cell used as the donor for the cloning of Dolly was taken from a mammary gland, and the production of a healthy clone therefore proved that a cell taken from a specific body part could recreate a whole individual. More specifically, the production of Dolly showed that mature differentiated somatic cells in an adult animal's body could under some circumstances revert back to an undifferentiated pluripotent form and then develop into any part of an animal.[4] As Dolly was cloned from part of a mammary gland, she was named after the famously busty country western singer Dolly Parton.[5]

Contents

[edit] Birth

The cloning process that produced Dolly.
The cloning process that produced Dolly.

Dolly was the end result of a long research program funded by the British government at the Roslin Institute in Scotland. This used the technique of somatic cell nuclear transfer, where the cell nucleus from an adult cell is transferred into an unfertilized oocyte that has had its nucleus removed. The hybrid cell is then stimulated to divide by an electric shock, and the blastocyst that is eventually produced is implanted in a surrogate mother. In the previous year, the same team had produced cloned sheep from embryonic cells,[6] but this was not seen as a breakthrough since adult cloned animals had been produced from embryonic tissue as long ago as 1958, using cells from the frog Xenopus laevis.[7] Dolly was the first clone produced from a cell taken from an adult animal. However, this cloning process is still highly inefficient, with Dolly the only lamb that survived to adulthood from 277 attempts. She is also recognised as one of the major stepping stones in the development of modern biology.[2]

[edit] Life

Dolly lived for her entire life at the Roslin Institute. There she was bred with a Welsh Mountain ram and produced four lambs in total. Her first lamb called Bonnie, was born in the spring of 1998. The next year Dolly produced twin lambs, and she gave birth to triplets in the year after that.[8] In the autumn of 2001, at the age of five, Dolly developed arthritis and began to walk stiffly, but this was successfully treated with anti-inflammatory drugs.[9]

[edit] Death

On February 14, 2003, Dolly was euthanised because of a progressive lung disease.[10] A Finn Dorset such as Dolly has a life expectancy of around 12 to 15 years, but Dolly lived to be only six years of age. An autopsy showed she had a form of lung cancer called Jaagsiekte that is a fairly common disease of sheep and is caused by the retrovirus JSRV.[11] Roslin scientists stated that they did not think there was a connection with Dolly's being a clone, and that other sheep in the same flock had died of the same disease.[10] Such lung diseases are a particular danger for sheep kept indoors, and Dolly had to sleep inside for security reasons.

However, some believe a contributing factor to Dolly's death was that she could have been born with a genetic age of six years, the same age as the sheep from which she was cloned. One basis for this idea was the finding that Dolly's telomeres were short, which typically is a result of the aging process.[12][13] However, the Roslin Institute have stated that intensive health screening did not reveal any abnormalities in Dolly that could have come from advanced aging.[14]

[edit] Legacy

After cloning was successfully demonstrated through the production of Dolly, many other large mammals have been cloned, including horses and bulls.[15] Cloning is now considered a promising tool for preserving endangered species and may be important in the future production of transgenic livestock.[16][17] Most animal conservation professionals point out that cloning does not alleviate the problems of loss of genetic diversity (see inbreeding) and habitat, and so 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 attempt to clone argali sheep did not produce viable embryos.[18] 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 cloned dog Snuppy was unfortunately associated with the Korean stem cell scandal involving Hwang Woo-Suk.

[edit] References

  1. ^ McLaren A (2000). "Cloning: pathways to a pluripotent future". Science 288 (5472): 1775–80. PMID 10877698. 
  2. ^ a b Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997). "Viable offspring derived from fetal and adult mammalian cells". Nature 385 (6619): 810–3. doi:10.1038/385810a0. PMID 9039911. 
  3. ^ "First cloned sheep Dolly dies at 6", CNN.com, 14 February 2003.
  4. ^ Pan GJ, Chang ZY, Schöler HR, Pei D (2002). "Stem cell pluripotency and transcription factor Oct4". Cell Res. 12 (5-6): 321–9. doi:10.1038/sj.cr.7290134. PMID 12528890. 
  5. ^ Dolly was world's hello to cloning's possibilities. usatoday (July 4, 2006). Retrieved on 2007-10-18.
  6. ^ Campbell KH, McWhir J, Ritchie WA, Wilmut I (1996). "Sheep cloned by nuclear transfer from a cultured cell line". Nature 380 (6569): 64–6. doi:10.1038/380064a0. PMID 8598906. 
  7. ^ Gurdon JB, Elsdale TR, Fischberg M (1958). "Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei". Nature 182 (4627): 64–5. PMID 13566187. 
  8. ^ Dolly's family Roslin Institute, Accessed 21 February 2008
  9. ^ Dolly's arthritis Roslin Institute, Accessed 21 February 2008
  10. ^ a b Dolly's final illness Roslin Institute, Accessed 21 February 2008
  11. ^ Palmarini M (2007). "A veterinary twist on pathogen biology". PLoS Pathog. 3 (2): e12. doi:10.1371/journal.ppat.0030012. PMID 17319740. 
  12. ^ Shiels PG, Kind AJ, Campbell KH, et al (1999). "Analysis of telomere length in Dolly, a sheep derived by nuclear transfer". Cloning 1 (2): 119–25. doi:10.1089/15204559950020003. PMID 16218837. 
  13. ^ Shiels PG, Kind AJ, Campbell KH, et al (1999). "Analysis of telomere lengths in cloned sheep". Nature 399 (6734): 316–7. doi:10.1038/20577. PMID 10360570. 
  14. ^ Was Dolly already 'old' at birth? Roslin Institute, Accessed 21 February 2008
  15. ^ Lozano, Juan A. (June 27, 2005). A&M Cloning project raises questions still. Bryan-College Station Eagle. Retrieved on 2007-04-30.
  16. ^ "Texas A&M scientists clone world’s first deer" (HTML), Innovations Report, 2003-12-23. Retrieved on 2007-01-01. 
  17. ^ Trounson AO (2006). "Future and applications of cloning". Methods Mol. Biol. 348: 319–32. PMID 16988390. 
  18. ^ Cloning Article (HTML). Retrieved on 2007-11-12.

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