1b. Dolly the sheep – the first cloned adult animal leading to multiple cloning business enterprises
Submitting InstitutionsUniversity of Edinburgh,
Unit of AssessmentAgriculture, Veterinary and Food Science
Summary Impact TypeTechnological
Research Subject Area(s)
Biological Sciences: Biochemistry and Cell Biology, Genetics
Medical and Health Sciences: Paediatrics and Reproductive Medicine
Summary of the impact
Impact: Economics. The first cloned mammal to be created from an
adult somatic cell and subsequent production of thousands of cloned
animals and their progeny.
Significance: The first evidence that adult specialized cells are
still capable of driving the development of a complete and fertile animal
which has been translated to preserve genetic characteristics of
exceptional value (e.g. competitiveness in horses)
Beneficiaries: Agriculture, livestock and equine industry,
Attribution: Essential improvements to the Somatic Cell Nuclear
Transfer (SCNT) technique by Prof. Wilmut (Roslin Institute, now part of
UoE) were used to clone Dolly the sheep.
Reach: Worldwide: SCNT technology has been adopted around the
world, being used to clone multiple animal species.
The productivity and profitability of animal farming is directly linked
to the quality of the livestock available. This in turn depends on the
underlying genetics of farm animals. For a long time, Ian Wilmut (employed
by Roslin Institute (Group Leader) and UoE (Inaugural Director of MRC
Centre for Regeneration and Professor) 1974-2011) and colleagues worked on
new methods to create genetically improved livestock by manipulation of
stem cells using nuclear transfer.
Research published in 1994 from the Roslin Institute (now part of the
University of Edinburgh), established that development of embryos
reconstructed by nuclear transfer is related to interactions between the
donor nucleus and the recipient cytoplasm at the time of fusion and during
the first cell cycle following reconstruction [3.1]. This observation led
to two protocols the team then followed for maintenance of normal ploidy,
using enucleated oocytes at metaphase II (MII) stage of cell division as
recipient cytoplasms (cytoplasts). The first was based on the transfer of
nuclei in G1, S or G2 phase of the cell cycle into MII cytoplasts devoid
of the so-called maturation-promoting factor (MPF) activity. The second
protocol used nuclei in G1 phase of the cell cycle and MII cytoplasts
containing high activity of MPF. A study in mice showed that it was
possible to use microtubule inhibitors such as nocodazole to hold cells in
mitosis before releasing them and using them as nuclear donors as they
were expected to be passing through G1 phase [3.2, 3.3].
The practical value of the second protocol was confirmed by the set of
experiments published in 1996 in which cells from sheep late blastocysts
were either taken at any stage of the cell cycle or were synchronised in
G0/G1 by serum starvation (as alternative to nocodazole). Whereas no lambs
were obtained without synchronisation, four live lambs were obtained
following transfer from late-passage cells at G0/G1 [3.4]. This was
followed by a final key experiment the following year, in which nuclei
arrested in G0/G1 were derived from a blastocyst, a foetus and,
critically, mammary tissue of an adult ewe. Live lambs were obtained from
all three populations, with the nuclei from mammary tissue creating Dolly
— the first cloned mammal made from an adult somatic cell [3.5].
References to the research
3.1) Campbell KH, Loi P, Cappai P, Wilmut I. (1994) Improved development
to blastocyst of ovine nuclear transfer embryos reconstructed during the
presumptive S-phase of enucleated activated oocytes. Biology of
Reproduction 50: 1385-1393. http://tinyurl.com/nc5lu36
3.2) Otaegui PJ, O'Neill GT, Campbell KH, Wilmut I. (1994) Transfer of
nuclei from 8-cell stage mouse embryos following use of nocodazole to
control the cell cycle. Molecular Reproduction and Development 39:
3.3) Otaegui PJ, Waddington D, Wilmut I. (1994) Nuclear transfer of
4-cell mouse embryos: synchronisation with cytoplast partially overcomes
nuclear donor cell-cycle effect. Journal of Reproduction and Fertility
Abstract Series 13 Abstract 67. (Copy of paper available on request.)
3.4) Campbell KH, McWhir J, Ritchie WA, Wilmut I. (1996) Sheep cloned by
nuclear transfer from a cultured cell line. Nature 380: 64-66. http://dx.doi.org/10.1038/380064a0
3.5) Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. (1997) Viable
offspring derived from fetal and adult mammalian cells. Nature 385:
Details of the impact
Somatic Cell Nuclear Transfer (SCNT) cloning is the only technology
available that enables generation of 99.8% genetically identical offspring
from selected individuals of adult animals (including sterilized animals).
As such, it is being exploited as an efficient multiplication tool to
support specific breeding strategies of farm animals with exceptionally
high genetic value.
Impact on commerce and agriculture
The SCNT technology has been widely adopted and used to create clones of
other animals (e.g. cows, deer, ferrets, goats, horses, mice, mules, pigs,
wolves, rats, rabbits, monkeys and water buffalo). Multiple new companies
have been established (e.g. Korean firm RNL Bio and US firm BioArts in
2008, and Kheiron in Argentina in 2012) and cloning plays increasingly
important role in the animal-breeding industry. For example in 2010 the
world's first cloned Polo pony was born [5.1]. Over 60 clones have been
generated since then, and one of the cloned ponies fetched $800,000 at an
auction in Argentina, which was attended by more than 1000 people (2010)
[5.1]. In June 2012, the Fédération Equestre Internationale (FEI) — the
group that governs international equestrian events, has lifted its ban on
cloned horses participating in competitions [5.1]. Consequently, cloned
horses will be allowed to participate in the Olympics beginning in 2016.
The FEI estimates that more than 110 horses were cloned in 2010 only.
First orders for commercial pet dog cloning were completed by the Korean
company RNL Bio and US firm BioArts in 2008 [5.2].
In January 2008, the US Food and Drug Administration (FDA) decided that
meat produced from clones and their progeny is acceptable for human
consumption [5.3]. Similar conclusions have been drawn by European Food
Safety Authority and published on 15 July 2008 (updated in 2012) [5.4].
There is already some use of cloned livestock in Europe, for example
several hundreds of cattle that are progeny of cloned ancestors live in
Switzerland [5.5], but animal cloning for food production in Europe meets
with considerable opposition. Use of cloned animals is more widespread in
Asia and America, where people are more accepting of consuming cloned
animal products [5.6].
Preserving diversity of livestock
The use of cloning from frozen somatic tissue is a much more
cost-effective strategy for bio-banking of endangered breeds than the
storage of sperm or egg cells. Sample collection and storage is easier and
cheaper, the technique can be deployed quickly in emergency situations
such as a disease outbreak, and cloning recovers all the genetic variation
of the donor — not just half of it as when using sperm. Consequently, SCNT
cloning of farm animals is a common new service in some countries
including the USA, Argentina and Brazil [5.7], and it is covered by all
major veterinary genetics and animal biotechnology textbooks [5.8, 5.9].
Cloning has been used to conserve several animal breeds in the recent
past. For example in 2012 an increasingly rare Himalayan pashmina goat
breed was successfully cloned. This important achievement, which was
performed in the frame of the National Agricultural Innovation Project
(NAIP) of the Indian Council of Agricultural Research, offers hope to the
people of Kashmir of increasing production of pashmina; a type of cashmere
wool. In Kashmir more than 10 million people are associated with $85
million shawl industry that depends on the availability of the
exceptionally fine wool produced by the rare animal [5.10].
Sources to corroborate the impact
5.1) Cloned ponies. http://tinyurl.com/om7nor5
5.2) "Dead dog's owner creates FIVE cloned puppies of her beloved pet"
Daily Mail August 5, 2008 http://tinyurl.com/nldstku
5.3) CVM GFI#179 "Use of Animal Clones and Clone Progeny for Human
Food/Animal Feed" U.S. Department of Health and Human Services, Food and
Drug Administration, Center for Veterinary Medicine, January 15, 2008.
5.4) Barlow S, Chesson A, Collins JD, Flynn A, Hardy A, Jany K, Knaap A,
Kuiper H, Le Neindre P, Schans J, Schlatter J, Silano V, Skerfving S and
Vannier P. "Food Safety, Animal Health and Welfare and Environmental
Impact of Animals derived from Cloning by Somatic Cell Nucleus Transfer
(SCNT) and their Offspring and Products Obtained from those Animals" The
EFSA Journal (2008) 767, 1-49. http://dx.doi.org/10.2903/j.efsa.2008.767
European Food Safety Authority. "Update on the state of play of Animal
Health and Welfare and Environmental Impact of Animals derived from SCNT
Cloning and their Offspring, and Food Safety of Products Obtained from
those Animals" The EFSA Journal (2012);10(7):2794.
5.5) Schweizerische Eidgenossenschaft, Federal Office of Public Health
"Food from cloned animals" (updated August 15, 2012) http://tinyurl.com/p4nb4s5
5.6) "In Europe and the US, consumer views on cloned products breed
different results" — news release from the Kansas State University (June
21, 2011) http://tinyurl.com/nn34hka
5.7) "Welfare implications of cloning of farm animals" — letter of Prof.
Christopher Wathes, Chairmen of the Farm Animal Welfare Committee (FAWC)
to Lord Taylor (Parliamentary Under Secretary, Department for Environment
and Rural Affairs) dated 11 April 2012. http://tinyurl.com/p2u36u4
5.8) Nicholas FW "Introduction to veterinary genetics" 3rd edition
Willey-Blackwell 2010. [Available on request.]
5.9) Singh B, Gautam SK, Chauhan S "Textbook of animal biotechnology",
Unit 4, The Energy and Resources Institute (TERI) 2013. [Final publication
5.10) "Pashmina goat clone boost for Kashmir's shawl makers" by Athar
Parvaiz, Asia Times Online, Apr 26, 2012. http://tinyurl.com/oeqbqn8