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Animal cloning 

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

Dolly was an ewe (July 5, 1996 – February 14, 2003) that 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. She was born on July 5, 1996 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

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 (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 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] 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. [8]

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.[9] 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.[10]

Death

On February 14, 2003, Dolly was euthanised because of a progressive lung disease.[11] 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. 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.[12] 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.[11] 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.[13] One basis for this idea was the finding that Dolly's telomeres were short, which typically is a result of the aging process.[14][15] However, the Roslin Institute have stated that intensive health screening did not reveal any abnormalities in Dolly that could have come from advanced aging.[13]

Legacy

After cloning was successfully demonstrated through the production of Dolly, many other large mammals have been cloned, including horses and bulls.[16] 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.[17] In 2005 a dog, Snuppy, was cloned by Korean stem cell researcher, Hwang Woo-Suk.

Cloning may eventually become a viable tool for preserving endangered species and could be important in the future production of transgenic livestock.[18][19] However, 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. 
  3. ^ a b "Dolly the sheep clone dies young", BBC News, Friday, 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. doi:10.1038/182064a0. PMID 13566187. 
  8. ^ Roger Highfield Dolly creator Prof Ian Wilmut shuns cloning Daily Telegraph 16/11/2007
  9. ^ Dolly's family Roslin Institute, Accessed 21 February 2008 Cached version
  10. ^ Dolly's arthritis Roslin Institute, Accessed 21 February 2008 Cached version
  11. ^ a b Dolly's final illness Roslin Institute, Accessed 21 February 2008 Cached version
  12. ^ Palmarini M (2007). "A veterinary twist on pathogen biology". PLoS Pathog. 3 (2): e12. doi:10.1371/journal.ppat.0030012. PMID 17319740. 
  13. ^ a b Was Dolly already 'old' at birth? Roslin Institute, Accessed 21 February 2008 Cached version
  14. ^ 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. 
  15. ^ 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. 
  16. ^ Lozano, Juan A. (June 27, 2005). "A&M Cloning project raises questions still". Bryan-College Station Eagle. Retrieved on 2007-04-30.
  17. ^ "Endangered sheep cloned". BBC News. Retrieved on 2007-11-12.
  18. ^ "Texas A&M scientists clone world’s first deer" (HTML), Innovations Report (2003-12-23). Retrieved on 2007-01-01. 
  19. ^ Trounson AO (2006). "Future and applications of cloning". Methods Mol. Biol. 348: 319–32. PMID 16988390. 

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