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Dolly (sheep)

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

Dolly (July 5, 1996 – February 14, 2003), was a female domestic sheep remarkable in being the first mammal 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. She was born on July 5, 1996 and she lived until the age of six,[3] and was dubbed "the world's most famous sheep" by Scientific American.[4]

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. As Dolly was cloned from part of a mammary gland, she was named after the famously busty country western singer Dolly Parton.[5]

Birth

The cloning process that produced Dolly.

This used the technique of Somatic cell nuclear transfer, where the cell nucleus from an adult cell is transferred into an unfertilised oocyte (developing egg cell) that has had its 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.

In the previous year, the same team had produced cloned sheep from the 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 mammal (the first animal cloned was an Asian carp in China in 1963 by Tong Dizhou).[8] The production of Dolly showed that genes in the nucleus of such a mature differentiated somatic cell are still capable of reverting back to an undifferentiated totipotent state, creating a cell that can then go on to develop into any part of an animal.[9] However, this reprogramming process is not perfect and embryos produced by nuclear transfer often show abnormal development.[10][11]

As a consequence of these difficulties in development, cloning mammals by nuclear transfer is still highly inefficient, with Dolly the only lamb that survived to adulthood from 277 attempts. However, her birth is still recognised as one of the major stepping stones in the development of modern biology.[2] 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.[12]


X RAY GOGLES ]==Life== Dolly lived for her entire life at the Roslin Institute. There she was bred with a Welsh Mountain ram and produced six lambs in total. Her first lamb called Bonnie, was born in April 1998.[3] 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.[13] 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.[14]

Death

On February 14, 2003, Dolly was euthanised because of a progressive lung disease and severe arthritis.[15] A Finn Dorset such as Dolly has a life expectancy of around 11 to 12 years, but Dolly lived to be only six years of age. A post-mortem examination 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.[16] 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.[15] Such lung diseases are a particular danger for sheep kept indoors, and Dolly had to sleep inside for security reasons.

However, some have 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 typically is a result of the aging process.[18][19] However, the Roslin Institute have 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 have been cloned, including horses and bulls.[20] 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 (a form of wild sheep), both resulting in viable offspring.[21] In 2005 a dog, Snuppy, was cloned by Korean stem cell researcher, Hwang Woo-Suk.

Cloning may become a viable tool for preserving endangered species. In January 2009, scientists from the Centre of Food Technology and Research of Aragon, in Zaragoza, northern Spain announced the cloning of the Pyrenean ibex, a form of wild mountain goat, which was officially declared extinct in 2000. Using DNA from skin samples kept in liquid nitrogen the scientists managed to clone the Ibex from domestic goat egg-cells. The newborn ibex died shortly after birth due to physical defects in its lungs. However, 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.[22] It has also increased the possibility that in the future it will be possible to reproduce long-dead species such as woolly mammoths and even dinosaurs.

Although cloning may eventually become a viable tool for preserving endangered species and important in the future production of transgenic livestock,[23][24] 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.

References

  1. ^ McLaren A (2000). "Cloning: pathways to a pluripotent future". Science. 288 (5472): 1775–80. doi:10.1126/science.288.5472.1775. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ a b "Dolly the sheep clone dies young", BBC News, Friday, 14 February, 2003
  4. ^ Lehrman, Sally (July 2008). "No More Cloning Around". Scientific American. Retrieved 2008-09-21.
  5. ^ "Dolly was world's hello to cloning's possibilities". usatoday. July 4, 2006. Retrieved 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. doi:10.1038/182064a0. PMID 13566187.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Liao L, Li L, Zhao RC (2007). "Stem cell research in China". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 362 (1482): 1107–12. doi:10.1098/rstb.2007.2037. PMC 2435574. PMID 17341453. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Niemann H, Tian XC, King WA, Lee RS (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Jaenisch R, Hochedlinger K, Eggan K (2005). "Nuclear cloning, epigenetic reprogramming and cellular differentiation". Novartis Found. Symp. 265: 107–18, discussion 118–28. doi:10.1002/0470091452.ch9. PMID 16050253.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Rideout WM, Eggan K, Jaenisch R (2001). "Nuclear cloning and epigenetic reprogramming of the genome". Science (journal). 293 (5532): 1093–8. doi:10.1126/science.1063206. PMID 11498580. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Roger Highfield Dolly creator Prof Ian Wilmut shuns cloning Daily Telegraph 16/11/2007
  13. ^ Dolly's family Roslin Institute, Accessed 21 February 2008 Cached version
  14. ^ Dolly's arthritis Roslin Institute, Accessed 21 February 2008 Cached version
  15. ^ a b Dolly's final illness Roslin Institute, Accessed 21 February 2008 Cached version
  16. ^ Palmarini M (2007). "A veterinary twist on pathogen biology". PLoS Pathog. 3 (2): e12. doi:10.1371/journal.ppat.0030012. PMID 17319740.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  17. ^ a b Was Dolly already 'old' at birth? Roslin Institute, Accessed 21 February 2008 Cached version
  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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  19. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  20. ^ Lozano, Juan A. (June 27, 2005). "A&M Cloning project raises questions still". Bryan-College Station Eagle. Retrieved 2007-04-30. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  21. ^ "Endangered sheep cloned". BBC News. Retrieved 2007-11-12.
  22. ^ "Extinct ibex is resurrected by cloning". The Telegraph. Retrieved 2009-02-01.
  23. ^ "Texas A&M scientists clone world's first deer" (HTML). Innovations Report. 2003-12-23. Retrieved 2007-01-01. {{cite news}}: Check date values in: |date= (help)
  24. ^ Trounson AO (2006). "Future and applications of cloning". Methods Mol. Biol. 348: 319–32. doi:10.1007/978-1-59745-154-3_22. PMID 16988390.
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