Dolly (sheep)

Dolly

Dolly's taxidermied remains
Other name(s) 6LLS (code name)
Species Domestic Sheep, Finn-Dorset
Sex Female
Born 5 July 1996
Roslin Institute, Edinburgh, Scotland
Died 14 February 2003 (aged 6)
Roslin Institute, Edinburgh, Scotland
Resting place National Museum of Scotland (remains on display).
Nation from United Kingdom (Great Britain)
Known for First mammal cloned from an adult somatic cell
Offspring Six lambs (Bonnie; twins Sally and Rosie; triplets Lucy, Darcy and Cotton)
Named after Dolly Parton[1]

Dolly (5 July 1996 – 14 February 2003) was a female domestic sheep, and the first mammal cloned from an adult somatic cell, using the process of nuclear transfer.[2][3] She was cloned by Sir Ian Wilmut, Keith Campbell and colleagues at the Roslin Institute, part of the University of Edinburgh, Scotland, and the biotechnology company PPL Therapeutics, based near Edinburgh. The funding for Dolly's cloning was provided by PPL Therapeutics and the Ministry of Agriculture.[4] She was born on 5 July 1996 and died from a progressive lung disease 5 months before her seventh birthday.[5] She has been called "the world's most famous sheep" by sources including BBC News and Scientific American.[6][7]

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 part of the body could recreate a whole individual. On Dolly's name, Wilmut stated "Dolly is derived from a mammary gland cell and we couldn't think of a more impressive pair of glands than Dolly Parton's".[1]

Birth

Dolly was born on 5 July 1996 and had three mothers (one provided the egg, another the DNA and a third carried the cloned embryo to term).[8] She was created using the technique of somatic cell nuclear transfer, where the cell nucleus from an adult cell is transferred into an unfertilized oocyte (developing egg cell) that has had its cell nucleus removed. The hybrid cell is then stimulated to divide by an electric shock, and when it develops into a blastocyst it is implanted in a surrogate mother.[9] Dolly was the first clone produced from a cell taken from an adult mammal. The production of Dolly showed that genes in the nucleus of such a mature differentiated somatic cell are still capable of reverting to an embryonic totipotent state, creating a cell that can then go on to develop into any part of an animal.[10] Dolly's existence was announced to the public on 22 February 1997.[1] It gained much attention in the media. A commercial with Scottish scientists playing with sheep was aired on TV, and a special report in TIME Magazine featured Dolly the sheep.[4] Science featured Dolly as the breakthrough of the year. Even though Dolly was not the first animal cloned, she received media attention because she was the first cloned from an adult cell.[11]

Life

The cloning process that produced Dolly

Dolly lived her entire life at the Roslin Institute in Edinburgh. There she was bred with a Welsh Mountain ram and produced six lambs in total. Her first lamb, named Bonnie, was born in April 1998.[5] The next year Dolly produced twin lambs Sally and Rosie, and she gave birth to triplets Lucy, Darcy and Cotton in the year after that.[12] In late 2001, at the age of four, Dolly developed arthritis and began to walk stiffly. This was treated with anti-inflammatory drugs.[13]

Death

On 14 February 2003, Dolly was euthanised because she had a progressive lung disease and severe arthritis.[14] A Finn Dorset such as Dolly has a life expectancy of around 11 to 12 years, but Dolly lived 6.5 years. A post-mortem examination showed she had a form of lung cancer called Jaagsiekte,[15] which is a fairly common disease of sheep and is caused by the retrovirus JSRV.[16] Roslin scientists stated that they did not think there was a connection with Dolly being a clone, and that other sheep in the same flock had died of the same disease.[14] Such lung diseases are a particular danger for sheep kept indoors, and Dolly had to sleep inside for security reasons.

Some in the press speculated that 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.[17] One basis for this idea was the finding that Dolly's telomeres were short, which is typically a result of the ageing process.[18][19] The Roslin Institute stated that intensive health screening did not reveal any abnormalities in Dolly that could have come from advanced aging.[17]

Legacy

After cloning was successfully demonstrated through the production of Dolly, many other large mammals were cloned, including pigs,[20][21] deer,[22] horses[23] and bulls.[24] The attempt to clone argali (mountain sheep) did not produce viable embryos. The attempt to clone a banteng bull was more successful, as were the attempts to clone mouflon (a form of wild sheep), both resulting in viable offspring.[25] The reprogramming process cells need to go through during cloning is not perfect and embryos produced by nuclear transfer often show abnormal development.[26][27] Making cloned mammals was highly inefficient - in 1996 Dolly was the only lamb that survived to adulthood from 277 attempts. However by 2014 Chinese scientists were reported to have 70–80% success rates cloning pigs[21] and in 2016, a Korean company, Sooam Biotech was producing 500 cloned embryos a day.[28] Wilmut, who led the team that created Dolly, announced in 2007 that the nuclear transfer technique may never be sufficiently efficient for use in humans.[29]

Cloning may have uses in preserving endangered species and may become a viable tool for reviving extinct species.[30] In January 2009, scientists from the Centre of Food Technology and Research of Aragon, in northern Spain announced the cloning of the Pyrenean ibex, a form of wild mountain goat, which was officially declared extinct in 2000. Although the newborn ibex died shortly after birth due to physical defects in its lungs, it is the first time an extinct animal has been cloned, and may open doors for saving endangered and newly extinct species by resurrecting them from frozen tissue.[31][32]

References

  1. 1 2 3 "1997: Dolly the sheep is cloned". BBC News. 22 February 1997.
  2. ↑ McLaren A (2000). "Cloning: pathways to a pluripotent future". Science 288 (5472): 1775–80. doi:10.1126/science.288.5472.1775. PMID 10877698.
  3. ↑ Wilmut I; Schnieke AE; McWhir J; Kind AJ; et al. (1997). "Viable offspring derived from fetal and adult mammalian cells". Nature 385 (6619): 810–3. Bibcode:1997Natur.385..810W. doi:10.1038/385810a0. PMID 9039911.
  4. 1 2 Edwards, J. (1999). "Why dolly matters: Kinship, culture and cloning". Ethnos 64 (3–4): 301–324. doi:10.1080/00141844.1999.9981606.
  5. 1 2 "Dolly the sheep clone dies young". BBC News. 14 February 2003
  6. ↑ "Is Dolly old before her time?". BBC News (London). 27 May 1999. Retrieved 4 October 2009.
  7. ↑ Lehrman, Sally (July 2008). "No More Cloning Around". Scientific American. Retrieved 21 September 2008.
  8. ↑ Williams, N. (2003). "Death of Dolly marks cloning milestone". Current Biology 13 (6): 209–210. doi:10.1016/S0960-9822(03)00148-9. PMID 12646139.
  9. ↑ Campbell KH; McWhir J; Ritchie WA; Wilmut I (1996). "Sheep cloned by nuclear transfer from a cultured cell line". Nature 380 (6569): 64–6. Bibcode:1996Natur.380...64C. doi:10.1038/380064a0. PMID 8598906.
  10. ↑ Niemann H; Tian XC; King WA; Lee RS (February 2008). "Epigenetic reprogramming in embryonic and foetal development upon somatic cell nuclear transfer cloning". Reproduction 135 (2): 151–63. doi:10.1530/REP-07-0397. PMID 18239046.
  11. ↑ McKinnell, Robert G.; Di Berardino, Marie A. (November 1999). "The Biology of Cloning: History and Rationale". BioScience 49 (11): 875–885. doi:10.2307/1313647. JSTOR 1313647.
  12. ↑ Dolly's family. Roslin Institute
  13. ↑ Dolly's arthritis. Roslin Institute, Accessed 21 February 2008
  14. 1 2 Dolly's final illness Roslin Institute, Accessed 21 February 2008 Cached version Archived October 30, 2012, at the Wayback Machine.
  15. ↑ Bridget M. Kuehn Goodbye, Dolly; first cloned sheep dies at six years old American Veterinary Medical Association, 15 April 2003
  16. ↑ Palmarini M (2007). "A Veterinary Twist on Pathogen Biology". PLoS Pathog. 3 (2): e12. doi:10.1371/journal.ppat.0030012. PMC 1803002. PMID 17319740.
  17. 1 2 Was Dolly already 'old' at birth? Roslin Institute, Accessed 4 April 2010
  18. ↑ 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.
  19. ↑ Shiels PG; Kind AJ; Campbell KH; et al. (1999). "Analysis of telomere lengths in cloned sheep". Nature 399 (6734): 316–7. Bibcode:1999Natur.399..316H. doi:10.1038/20580. PMID 10360570.
  20. ↑ Grisham, Julie (April 2000). "Pigs cloned for first time". Nature Biotechnology 18 (4): 365. doi:10.1038/74335.
  21. 1 2 Shukman, David (14 January 2014) China cloning on an 'industrial scale' BBC News Science and Environment, Retrieved 14 January 2014
  22. ↑ "Texas A&M scientists clone world’s first deer". Innovations Report. 23 December 2003. Retrieved 1 January 2007.
  23. ↑ Cohen, Haley (31 July 2015). "How Champion-Pony Clones Have Transformed the Game of Polo". VFNews. Vanity Fair. Retrieved 27 December 2015.
  24. ↑ Lozano, Juan A. (27 June 2005). "A&M Cloning project raises questions still". Bryan-College Station Eagle. Retrieved 30 April 2007.
  25. ↑ "Endangered sheep cloned". BBC News (London). 1 October 2001. Retrieved 12 November 2007.
  26. ↑ Jaenisch R; Hochedlinger K; Eggan K (2005). "Nuclear cloning, epigenetic reprogramming and cellular differentiation". Novartis Found. Symp. Novartis Foundation Symposia 265: 107–18; discussion 118–28. doi:10.1002/0470091452.ch9. ISBN 978-0-470-09145-6. PMID 16050253.
  27. ↑ Rideout WM; Eggan K; Jaenisch R (August 2001). "Nuclear cloning and epigenetic reprogramming of the genome". Science 293 (5532): 1093–8. doi:10.1126/science.1063206. PMID 11498580.
  28. ↑ Zastrow, Mark (8 February 2016). "Inside the cloning factory that creates 500 new animals a day". New Scientist. Retrieved 23 February 2016.
  29. ↑ Roger Highfield "Dolly creator Prof Ian Wilmut shuns cloning". Daily Telegraph 16 November 2007
  30. ↑ Trounson AO (2006). "Future and applications of cloning". Methods Mol. Biol. Methods in Molecular Biology 348: 319–32. doi:10.1007/978-1-59745-154-3_22. ISBN 978-1-58829-280-3. PMID 16988390.
  31. ↑ Gray, Richard; Dobson, Roger (31 January 2009). "Extinct ibex is resurrected by cloning". The Telegraph (London). Retrieved 1 February 2009.
  32. ↑ Jabr, Ferris (11 March 2013) Will Cloning Ever Save Endangered Animals? Scientific American, Retrieved 15 January 2014

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