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Food Standards Agency FSA 10/12/04

Open Board – 7 December 2010

ANIMAL CLONING FOR FOOD PRODUCTION

Report by Alison Gleadle, Director of Food Safety

1 SUMMARY

1.1 This paper provides the Board with an update on recent developments in relation
to the cloning of animals for food production.

1.2 The Board is asked if it wishes to update its advice to Ministers, on foods
obtained from the use of cloning technology, in the light of the updated evidence
base.

2 INTRODUCTION

2.1 The Board considered animal cloning at its open meeting in September 2010
(paper FSA 10/09/05). At that meeting, the Board agreed the following points:

• The FSA’s primary objective in responding to this challenge is to ensure that food
safety is not compromised by any novel food or process. The available evidence
is that food (milk and meat) derived from the progeny of cloned cattle and pigs
represents no different risk to food safety to that which is from traditionally-bred
animals.
• As always, if that evidence changes, the FSA’s advice to consumers and
government would change as necessary. The Board is keen to maintain a high
level of scrutiny of the science and evidence as it emerges.
• The FSA should not attempt to regulate any process or practice which cannot be
traced or measured to an acceptable level of confidence. In this case it would be
disproportionate to try to establish a monitoring process (whose purpose would
be to ensure the safest possible food), where there is no discernible risk and with
the knowledge that it would only be feasible for a very small proportion of the
market. In the absence of traceability, the only other option would be a ban which
would be entirely inappropriate given the current evidence of risk to human
health.
• The Board will advise agriculture ministers that they should commission the
appropriate bodies to investigate further the ethical and welfare concerns that
have been an important feature of consumer concerns. The FSA would be keen
to be involved in any consumer dialogue.
• Legislation should be consistent and harmonised across the EU and any
uncertainties in interpretation should be rapidly resolved.
• In the absence of an actual application for authorisation of meat or milk derived
from the progeny of cloned cattle, the Board requested that the Executive should

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Open Board – 7 December 2010

commission the Advisory Committee on Novel Foods and Processes (ACNFP) to


conduct a hypothetical assessment.

2.2 The Chair and Chief Executive have met Defra Ministers (England) and have
presented the Board’s conclusions. Devolved Ministers have been informed of
the Board’s conclusions in writing, and made no comments.

3 STRATEGIC AIMS

3.1 Work related to the use of animal cloning for food production meets strategic
aims 1 and 2, namely any food produced in, or imported into, the UK is safe to
eat.

4 DISCUSSION

4.1 The following information has become available since the Board’s discussion in
September:
• The European Food Safety Authority (EFSA) has published a statement that
updates its earlier opinion on cloned animals and their offspring.
• The European Commission has published its report on animal cloning for food
production, including recommendations for future EU legislation in this area.
• Government Ministers have considered cloning, the Board’s advice and the
Commission’s report and have agreed a UK position on the Commission’s
recommendations.
• The ACNFP has considered the available data on milk and meat from cloned
animals and their descendants.

EFSA statement
4.2 Following its 2008 review of the implications of the technology, which was
updated in 2009, EFSA received a request from the European Commission in
May 2010 for a further update on scientific developments into the use of animal
cloning for food production purposes (FSA10/09/05 para 4.3). The Commission
also asked whether there were any new data available regarding the health and
welfare of cloned animals.
4.3 On 17 September 2010 EFSA published a further statement (Annex A) reporting
that, in terms of food safety, the composition of meat and milk from cloned
animals is no different to that produced by conventionally reared animals,
consistent with the conclusions in its original 2008 opinion. EFSA noted that
there were limited data for species other than cattle and pigs. There were no new
data on the health and welfare of cloned animals for food production that would
alter its previous conclusions in relation to food safety or animal health and
welfare aspects of animal cloning.

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European Commission report


4.4 In 2008 the European Parliament issued a resolution calling on the European
Commission to submit a proposal to prohibit the use of animal cloning in the food
chain, citing concerns relating to animal health and welfare, loss of genetic
diversity and risk to the image of European agriculture. In response, Ministers
from EU Member States requested that the Commission prepare a report on food
production from cloned animals (FSA10/09/05 paragraph 4.22).
4.5 The Commission’s report (Annex B) was published on 19 October and reviews
the current position in relation to:
• animal welfare and ethical considerations
• the use of cloning in the EU and other countries
• public perception and stakeholder views
• trade issues and legal aspects.

4.6 The Commission proposes a temporary (5 year) suspension of animal cloning for
food production, the use of clones and the marketing of food from clones in the
EU. The report does not recommend any restrictions on the use of the immediate
offspring or later descendants of clones or on the marketing of food obtained from
such animals, although it proposes that imports of semen and embryos derived
from clones and imported from outside the EU should be identified as such on
import certificates so that farmers and industry can set up traceability systems
that would enable animals descending from clones to be tracked, should they
wish to do so.

4.7 This report is currently being considered by the European Parliament and by
Member States

UK Government Position
4.8 In September, the Board was informed that the UK Government would, in the
near future, need to establish its position on cloning, in advance of further
negotiations and discussions in Brussels, taking account of food safety and
consumer choice, as well as animal welfare, implications for international trade
and ethical considerations.
4.9 The Government’s general view is that all regulation should be proportionate and
enforceable, safeguarding the principles of food safety and consumer choice and
guided by the principles of better regulation and evidence-based decision-
making. It recognises that cloning is not a traditional breeding technique and, as
such, accepts that, under the EU Novel Foods Regulation 258/97, approval
should be sought before food from clones themselves can be marketed.
4.10 The Government recognises that cloning is a relatively new technique and that
the welfare of clones and of their surrogate dams must be protected. However,
existing EU legislation is considered sufficient to deal with welfare issues.

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4.11 For the future, the Government considers that a ban or a temporary suspension
on cloning, the use of cloned animals and the marketing of food from cloned
animals would be disproportionate in terms of food safety and animal welfare.
The UK therefore does not support the Commission’s recommendations for the
temporary suspension of animal cloning for food production because insufficient
evidence has been provided to justify a ban. The Government would need to see
an impact assessment that demonstrated the need for and benefit of new
regulation. However, the Government considers that controls should not apply to
immediate offspring of cloned animals or to later generations, where these are
conceived by traditional breeding techniques.
4.12 The Government also questions the value of the proposed traceability system for
imported semen and embryos from cloned animals, as this would not deal either
with offspring of clones already present within the EU or with imported food
derived from animals with clones in their ancestry.

ACNFP discussion
4.13 At the 15 September meeting Board Members noted that no applications for the
approval of food from cloned animals (or their descendants) have been made
under the EU regulation on novel foods, and asked that the ACNFP be
approached to conduct a hypothetical assessment.
4.14 At their meeting on 25 November, held in open session, the ACNFP reviewed the
available data, presented in the style of a novel food application. The discussion
paper is published on the ACNFP’s website and the meeting was attended by
observers from the general public and by the Agency’s Chief Scientist. The
Committee concluded that:

• the evidence showed no differences in composition between the meat and milk
of conventional animals, clones or their progeny, which is therefore unlikely to
present any food safety risk.

• the current evidence on the composition of meat and milk is relatively limited,
and further evidence is required on how the rearing of animals in different
environments may affect the meat and milk.

• any potential differences between conventional cattle and the progeny of a clone
were unlikely to exist from the second generation onwards.

• consumers may want to see effective labelling of products from clones and their
offspring.
4.15 The draft minutes of the Committee’s discussion are attached at Annex C.

5 LEGAL IMPLICATIONS

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5.1 The previous paper noted that the wording of the Novel Foods Regulation
(Regulation EC 258/97) is not explicit in respect of descendants of non-
traditionally bred animals. The Agency’s interpretation has been that food
obtained from offspring and later descendants of cloned animals falls within the
scope of “novel foods”. Others including the European Commission take a
narrower view and consider that the regulation applies only to cloned animals
themselves, so that food from descendants of clones can be freely marketed
without the need for assessment and authorisation.

5.2 The Agency is continuing to review the legal issues associated with this point of
interpretation of the current regulation, in consultation with other Government
Departments. In the meantime the Agency’s interpretation is unchanged.

6 CONCLUSION AND RECOMMENDATION

6.1 The Board is invited to consider the new information that has become available
since its earlier discussion and to consider the following questions:

In respect of food safety:


• Does the Board agree that the marketing of products obtained from cloned
animals should be subject to authorisation as novel foods; but that there
are no food safety grounds for regulating foods from the descendants of
clones?
• Subject to legal opinion, should the FSA now adopt the stance taken by
the European Commission and others, that food obtained from the
descendants of clones does not require authorisation under the novel
foods regulation?
• Does the Board wish to press the European Commission for formal
clarification on the relative status of food from clones and their
descendants under existing legislation?

In respect of other consumer interests:


• Does the Board agree that, for food safety purposes, mandatory labelling
of meat and milk obtained from the descendants of cloned animals would
be unnecessary and disproportionate, providing no significant consumer
benefit?
• Does the Board wish to ask Defra and its devolved equivalents to consider
what information about animal cloning should be provided to the public
about ethics and welfare?

For further information contact Sandy Lawrie on 020 7276 8565, email
sandy.lawrie@foodstandards.gsi.gov.uk

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Food Standards Agency FSA 10/12/04
Open Board – 7 December 2010

ANNEX C

Draft minutes of ACNFP discussion (25 November 2010)

Meat and Milk from Cloned Animals and their Progeny   ACNFP/100/7 

Members considered a hypothetical application for the authorisation of meat and milk from cloned 
cattle and their descendants. The paper had been prepared by the Secretariat following a request from 
the FSA Board that the ACNFP be asked to consider the safety of food from cloned animals and their 
descendants 

Introducing the paper, the Secretary highlighted an error in paragraph 14, as the FDA had highlighted 
individual data points lying outside the control range, rather than statistically significant differences.  At 
paragraphs 29 and 32 the reference to “cloned animals” should read “cloned animals and their 
descendants”.  

Members commented that the available data did not show any differences in the composition of meat 
and milk from cloned animals and their conventionally bred counterparts. However, Members noted 
that the compositional data were limited to a small number of breeds reared under relatively controlled 
conditions and that it would be useful if additional studies were carried out which investigated potential 
differences under a wider range of environmental conditions.  On the basis of the limited information on 
composition, Members agreed with the conclusions of both the FDA and EFSA that safety concerns 
arising as a result of epigenetic reprogramming were unlikely, but as there were reports that 
environmental factors could exert an influence on epigenetic status, additional data from the progeny of 
clones under a range of production conditions would provide reassurance on this point. 

In relation to allergenicity, Members noted that epigenetic effects on post‐translational modification 
could theoretically influence the allergenic potential of expressed proteins in meat and milk but that 
there was no evidence for such effects in the offspring of clones. 

Members agreed that epigenetic effects could potentially occur in cloned animals and their immediate 
offspring, through effects on imprinting in particular, but current understanding of epigenetic 
inheritance suggests that these effects were unlikely to persist in subsequent generations produced 
using traditional breeding practices.  

The Committee advised that, in view of the level of public concern, particularly with respect to animal 
welfare, the provision of effective labelling on products from cloned animals and their immediate 
descendants was important, but there was a need to define how many generations this should apply to. 

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EFSA Journal 2010:8(9):1784

STATEMENT OF EFSA

Update on the state of play of animal cloning1


European Food Safety Authority2, 3

European Food Safety Authority (EFSA), Parma, Italy

ABSTRACT
The European Food Safety Authority (EFSA) received in May 2010, a request from the European Commission
for an update on the state of play of the possible scientific developments on the issue of cloning of farmed
animals for food production purposes. The present statement follows the EFSA 2009 statement and EFSA 2008
scientific opinion and is based on a review of identified peer reviewed scientific literature up to 1 July 2010,
information made available to EFSA following a call for data, discussion with experts in the field of animal
cloning and a peer review by external experts. Based on the literature search and information provided, it is
concluded that there is still limited information available on species other than cattle and pigs which would
allow for assessment of food safety and animal health and welfare aspects. Cloning efficiency in cattle (currently
around 10 %) and pigs (currently around 6 %) is lower than by natural breeding (cattle calving rate 40-55 %) as
well as from assisted reproductive technologies (ART), such as artificial insemination. However, compared with
in vitro produced embryos and embryo transfer in pigs, cloning has similar efficiency (~ 6 %). No new
information has become available, since the EFSA 2009 statement and the EFSA 2008 scientific opinion that
would lead, at this point in time, to a reconsideration of the conclusions and recommendations related to the food
safety, animal health and welfare aspects of animal cloning as considered in the 2008 scientific opinion and the
EFSA 2009 statement. © European Food Safety Authority, 2010

KEY WORDS
SCNT, Somatic Cell Nuclear Transfer, Efficiency, Safety, Cattle, Pig

1 On request from the European Commission, Question No EFSA-Q-2010-00887, issued on 14-09-2010


2 Correspondence: scientic.committee@efsa.europa.eu
3 Acknowledgement: EFSA wishes to thank the Scientific Committee members and external peer reviewers for reviewing
the statement and EFSA staff David Carlander for the support provided to this scientific output.

Suggested citation: European Food Safety Authority; Update on the state of play of animal cloning. EFSA Journal
2010:8(9):1784. [21pp.] doi:10.2903/j.efsa.2010.1784. Available online:www.efsa.europa.eu/efsajournal.htm

© European Food Safety Authority, 2010 1


Update on Animal Cloning 2010

SUMMARY
The European Food Safety Authority (EFSA) received in May 2010, a request from the European
Commission for an update on the state of play of the possible scientific developments on the issue of
cloning of farmed animals for food production purposes and taking into consideration existing data
from European research centres about the health and welfare of clones during their production life and
natural life span.

The present statement follows the EFSA 2009 statement and EFSA 2008 scientific opinion and is
based on a review of identified peer reviewed scientific literature up to 1 July 2010, information made
available to EFSA following a call for data, discussion with experts in the field of animal cloning and
a peer review by external experts. The focus of the statement has been to evaluate information related
to aspects of food safety, health and welfare of animal clones and their offspring.

The EFSA 2008 scientific opinion concluded that epigenetic dysregulation is considered to be the
main source of adverse effects that may affect clones and result in developmental abnormalities. The
health and welfare of a significant proportion of clones, mainly within the juvenile period for bovines
and perinatal period for pigs, have been found to be adversely affected, often severely and with a fatal
outcome. The use of cloning by SCNT (Somatic Cell Nuclear Transfer) in cattle and pigs, has also
produced healthy clones and healthy offspring that are similar to their conventional counterparts based
on parameters such as physiological characteristics, demeanour and clinical status. In relation to food
safety, there is no indication that differences exist for meat and milk of clones and their progeny
compared with those from conventionally bred animals. The EFSA 2009 statement confirmed that the
conclusions and recommendations of the EFSA 2008 scientific opinion were still valid.

Based on the literature search and information provided in the framework of the present statement, it is
concluded that there is still limited information available on species other than cattle and pigs which
would allow for assessment of food safety and animal health and welfare aspects.

Information, published over several years, indicate that cloning efficiency in cattle (currently around
10 %) and pigs (currently around 6 %) is lower than by natural breeding (cattle calving rate 40-55 %)
as well as from assisted reproductive technologies (ART), such as artificial insemination. However,
compared with in vitro produced embryos and embryo transfer in pigs, cloning has similar efficiency
(~ 6 %).

In vitro fertilisation technologies can deliver healthy animals using similar in vitro handling steps (e.g.
maturation, culture) to those used in cloning, but at a higher rate, especially in cattle. This suggests
that the reprogramming of the somatic donor cell nucleus (epigenetic dysregulation) is a major factor
affecting cloning efficiency. If the success rate of the epigenetic reprogramming is improved it is
expected that the pathologies and mortalities observed in a proportion of clones would decrease
(EFSA 2009).

No new information has become available, since the EFSA 2009 statement and the EFSA 2008
scientific opinion that would lead, at this point in time, to a reconsideration of the conclusions and
recommendations related to the food safety, animal health and welfare aspects of animal cloning as
considered in the 2008 scientific opinion and the EFSA 2009 statement.

EFSA Journal 2010:8(9):1784 2


Update on Animal Cloning 2010

TABLE OF CONTENTS
Abstract .................................................................................................................................................... 1 
Summary .................................................................................................................................................. 2 
Table of contents ...................................................................................................................................... 3 
Request as provided by European Commission ....................................................................................... 4 
Evaluation................................................................................................................................................. 5 
1.  Preparation of the update on the state of play of animal cloning (SCNT)....................................... 5 
1.1.  EFSA scientific opinion of 2008 and EFSA statement of 2009.............................................. 5 
1.2.  Collection of relevant data and information to prepare the statement .................................... 5 
2.  General information on cloning and cloning research ..................................................................... 6 
2.1.  Applications of cloning ........................................................................................................... 6 
2.1.1.  Breeding elite animals ........................................................................................................ 7 
2.1.2.  Reproducing transgenic animals ......................................................................................... 7 
2.1.3.  Preservation of extinct animals and genetic diversity ........................................................ 7 
3.  Update on the state of play of cloning ............................................................................................. 7 
3.1.  In vitro studies, embryo development ..................................................................................... 7 
3.2.  Aberrant gene expression in placenta ..................................................................................... 8 
3.3.  Surrogate dam and uterine function ........................................................................................ 9 
3.4.  Cattle clones ............................................................................................................................ 9 
4.  Food safety of products from clones ............................................................................................. 10 
5.  Offspring of clones ........................................................................................................................ 10 
6.  Breeding and cloning efficiency .................................................................................................... 11 
6.1.  Efficiency of ART other than cloning .................................................................................. 11 
6.2.  Efficiency of cattle cloning ................................................................................................... 12 
6.3.  Efficiency of pig cloning ...................................................................................................... 12 
6.4.  Conclusion on cloning efficiency ......................................................................................... 13 
Conclusions ............................................................................................................................................ 13 
Documentation provided to EFSA ......................................................................................................... 15 
References .............................................................................................................................................. 15 
Appendix 1.   Conclusions and Recommendations from the EFSA 2008 Scientific Opinion .......... 19 
Appendix 2.   Summary of EFSA 2009 statement ............................................................................ 21 
 

EFSA Journal 2010:8(9):1784 3


Update on Animal Cloning 2010

REQUEST AS PROVIDED BY EUROPEAN COMMISSION


The European Commission letter with the request is found in the EFSA register of questions which is
available on the EFSA website:

European Commission request to the European Food Safety Authority for an update on the
state of play of animal cloning (SCNT)

During the hearings in the European Parliament, Commissioner Dalli undertook to present a report on
cloning to the European Parliament and to the Council by the end of this year. The report shall provide
details on the market situation of cloned animals, their offspring, breeding material and food products
obtained from such animals. It will review all the science based issues concerning the health and
welfare of the animals as well as food safety issues. It will elaborate on the possible benefits of the
technology for livestock breeding and go deeper into the analysis of the factors influencing societal
acceptance of new technologies.

The EFSA Statement of July 2009 confirmed the EFSA Opinion of January 2008. The Commission
would again appreciate an updated assessment of the current situation as regards the scientific
development in this area.

By this letter, I would like to formally request an update on the state of play on the possible scientific
developments from the European Food Safety Authority on the issue of cloning of farmed animals for
food production purposes.

The European Commission requests information of the European Food Safety Authority on existing
data from European research centres about the health and welfare of clones during their production life
and natural life span.

I would appreciate the update by the end of July 2010.

[Signed]

EFSA Journal 2010:8(9):1784 4


Update on Animal Cloning 2010

EVALUATION

1. Preparation of the update on the state of play of animal cloning (SCNT)


The European Food Safety Authority (EFSA) received on 11th May 2010 a request from the European
Commission for an update on the state of play of the possible scientific developments on the issue of
cloning of farmed animals for food production purposes and to consider existing data from European
research centres about the health and welfare of clones during their production life and natural life
span. The present statement follows the EFSA 2009 statement and EFSA 2008 scientific opinion and
is based on a review of identified peer-reviewed scientific literature up to 1 July 2010 and additional
information made available to EFSA following a call for data, discussion with experts in the field of
animal cloning and a peer review by the Scientific Committee and external experts.

It should be noted that this statement is not a full review of all papers published regarding cloning of
animals, as the reviewed studies were often not designed to evaluate food safety, animal health and
welfare of animal clones. The present statement does not address transgenic animals reproduced by
cloning, but use some information from scientific literature on transgenic clones, which is indicated in
the statement.

Section 2 of the statement shortly describes generally research on cloning and applications of the
technology. Section 3 is an update of the published information and deal with animal health and
welfare aspects which is followed by section 4 dealing with information related to food safety and
section 5 has information on offspring of clones. The last section of the statement addresses breeding
and cloning efficiency. This section, although not specifically required in the terms of reference, has
been included based on discussions with the European Commission services. Information related to
this section has been gathered from publications published over several years.

1.1. EFSA scientific opinion of 2008 and EFSA statement of 2009


This statement builds on the previous Scientific Opinion of the Scientific Committee on a request from
the European Commission on 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 adopted in July 2008 (EFSA, 2008), and on the Statement of
EFSA prepared by the Scientific Committee and Advisory Forum Unit on Further Advice on the
Implications of Animal Cloning (SCNT) issued in June 2009 (EFSA, 2009). The conclusions and
recommendations of the 2008 scientific opinion and the summary of the 2009 statement are found in
appendices 1 and 2.

1.2. Collection of relevant data and information to prepare the statement


To collect data and information in relation to the request from the European Commission EFSA
launched a call for data on its website from 9 June to 9 July 2010. Dedicated dissemination of the call
for data was also carried out via the EFSA Advisory Forum and the EFSA Focal Points as well as with
targeted e-mail to various research groups both within and outside the EU. At the closing of the call
contributions were received from nine sources. A list of the contributions made available to EFSA can
be found at the end of the statement. Information for this statement was also collected during a
telephone conference with members of the former EFSA working group on animal cloning who
participated in the preparatory work for the 2008 scientific opinion.

In addition to the call for data a comprehensive literature search was performed. The search strategy
was based on keywords from the EFSA 2008 scientific opinion and 2009 statement. The search was in
general aimed at finding publications since 1st May 2009 as publications up to this date were already
included in the search for the EFSA 2009 statement. The literature searches in the databases were

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Update on Animal Cloning 2010

concluded on 1st July 2010. The search aimed at identifying publications in publicly available
databases, mainly Pubmed, ScienceDirect and ISI Web of Knowledge. The literature search included
some information presented as abstracts.

The initial literature search retrieved about 400 papers which after screening and further selection were
reduced to about 100 papers that were assessed in more detail. The assessment of the retrieved
information in general excluded several types of studies; transgenic animals, inter-species cloning,
studies focusing on methodological developments and improvements and studies involving non-farm
animals such as rats and mice. Studies where no live-born animals were reported were in general not
considered as the design of many of such studies was not aimed at delivering animals, but to study e.g.
in vitro development of embryos.

2. General information on cloning and cloning research


Research on cloning performed by universities and research institutions is mainly focused on
understanding the early steps in embryo development and epigenetic reprogramming by making use of
SCNT as a useful technology to develop research models (Rosenfeld, 2009). This basic research aims
at clarifying the underlying biological mechanisms and is not necessarily focused on producing live
animal clones. Academic research aims also at improving cloning protocols to increase the cloning
efficiency as well as attempts to clone species that have not been cloned before. As cloning research is
resource intensive, samples and replications are often small and the keeping of live animals for long
periods is not always economically feasible. Private companies involved in research mainly aim at
improving efficiency of the cloning technology, but it should be noted that private research and
method development is unlikely to be published in detail in view of the proprietary nature of the data
and confidential business information.

Identifying and clarifying the underlying mechanisms involved in cloning is a complex task and the
alterations observed in many cloning experiments can arise from a diverse range of factors including
donor cell type, cell cycle stage, nuclear transfer protocol, source of the oocyte, embryo culture
system, embryo stage, surrogate dam preparation and operators’ skills. The failures observed in
cloning can be traced to epigenetic alterations, specifically failures in chromatin remodelling and DNA
and histone methylation (EFSA 2008 and 2009).

The number of born somatic cell cloned animals has increased worldwide into the thousands and the
technique has been successfully used in at least 22 different species (sheep, cattle, mouse, pig, goat,
deer, horse, mule, rat, domestic cat, African wildcat, sand cat, dog, wolf, water buffalo, rabbit,
European mouflon, ferret, gaur, ibex, camel and Indian buffalo). Most cloning laboratories are
working on farm animals such as cattle, pig, goat, sheep, buffalo and horse.

SCNT in cattle dominate publications, accounting for an annual average of about 25 % of PubMed-
listed cloning papers since 1994. Pig is the second most important cloned farm animal by this measure
(13 % publications), followed by goat, sheep, buffalo and red deer (altogether 6 %). Overall, farm
animal cloning thus accounts for 44 % of cloning publications, laboratory animals (mouse, rabbit,
monkey and rat) for 22 %, other species (including human) for 16 % and general review articles,
which are not species-specific, for the remaining 18 %. Based solely on past research investment and
output, i.e. the number of laboratories involved and their publications, cattle are the most important
cloned livestock species (Oback, 2009).

2.1. Applications of cloning


There are mainly three general applications of cloning outside fundamental research; producing elite
animals, reproducing transgenic animals and preservation of extinct animals and genetic diversity.

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Update on Animal Cloning 2010

2.1.1. Breeding elite animals


Being a genetic copy of its cell donor, the clone has similar potential productive performances. It
should be stressed that besides quantitative/qualitative traits of animal products like milk volume or
lean meat, today’s selection strategies take into account other relevant parameters, including resistance
to the common pathologies (e.g. mastitis, other infectious and parasitic diseases), fertility, mentality
and others related to the general robustness of the animal (e.g. lameness). Breeding out such complex
traits using the traditional selection schemes is time consuming and might turn out to be complicated
and the success is not certain. Cloning could contribute to address these issues in a more rapid manner.
The clones are then multiplied using conventional breeding methods.

2.1.2. Reproducing transgenic animals


SCNT represents a useful tool for reproducing transgenic animals (genetically modified animals)
(Laible, 2009). Transgenic animals are mainly used in research or for production of pharmaceutical
substances. This statement does not address transgenic animals produced by cloning.

2.1.3. Preservation of extinct animals and genetic diversity


An argument often voiced is that cloning will decrease genetic diversity. However, if used
appropriately, in connection with suitable management measures, cloning is not expected to adversely
affect the genetic diversity among domestic species (EFSA 2008). It is appropriate to recall that the
last century has seen a dramatic reduction of animal species, mostly large mammals, mainly caused by
human-related activities. The obvious consequence of such phenomenon is the progressive contraction
in biodiversity. Paradoxically, this problem does not involve wild species only, but also domestic
ones, often local breeds perfectly adapted to particular ecotypes, being substituted by a few more
productive phenotypes. According to the Food and Agriculture Organization of the United Nations,
1491 (around 20 %) of the reported 7616 livestock breeds are classified as being critically endangered,
critical-maintained, endangered, or endangered-maintained (FAO, 2007).

3. Update on the state of play of cloning


There is still limited information available on species other than cattle and pigs which would allow for
a risk assessment. There are, for example, no identified compositional analyses of meat other than
from cattle and pigs. It is currently impossible to prevent the development of all pathologies associated
with clone pregnancies, which does not mean that all clone pregnancies result in pathologies of the
newborns (IETS Manual 4th Edition 2010).

In vitro fertilisation technologies can deliver healthy animals using similar in vitro handling steps (e.g.
maturation, culture) to those used in cloning, but at a higher rate, especially in cattle. This suggests
that the reprogramming of the somatic donor cell nucleus (epigenetic dysregulation) is a major factor
affecting cloning efficiency. If the success rate of the epigenetic reprogramming is improved it is
expected that the pathologies and mortalities observed in a proportion of clones would decrease
(EFSA 2009).

3.1. In vitro studies, embryo development


Several publications, mainly from academia, are related to fundamental research and address various
aspects of the initial steps in the cloning process. They investigate biological mechanisms and
optimisation of oocyte and donor cell preparation, cellular transfer procedures and the in vitro embryo
culture and development. There are also studies investigating the epigenetic reprogramming and
comparing SCNT embryos, usually up to the blastocyst stage in cattle with other assisted reproductive
technologies (ART) and with conventional breeding. Many of these studies are designed to investigate

EFSA Journal 2010:8(9):1784 7


Update on Animal Cloning 2010

only the in vitro stage. The in vivo stage, i.e. after embryo transfer to a surrogate dam, is usually not
considered. Results support among others, the hypothesis that abnormalities in the expression of
imprinted genes are the causes of the low cloning efficiency and the epigenetic dysregulation.

The choice of donor cell type impacts on the cloning efficiency but no conclusive method how to
select the most usable cell line has been presented, also because several other factors have an effect,
e.g. the choice of cloning protocol (McLean et al., 2010; Oback, 2009). ViaGen Inc, a USA based
commercial cloning company, has submitted unpublished information indicating that there is a wide
variability between cell lines, where certain cell lines exhibit much higher cattle calving rate and day
60 healthy calf rate, compared with the average of other cell lines used by ViaGen (Figure 1). This
confirms previous data published by Panarace (Panarace et al., 2007).
% of live calves 

Gestation days ‐ days of live calves 

Figure 1: Cell line variability and calving rate


Eight percent of ViaGen cell lines (18/220) have produced 20 % to 40 % live calves at day 60. Unpublished information
from ViaGen Inc, USA.

Cloned piglets have been produced from pig bone marrow-derived mesenchymal stem cells, a more
pluripotent cell stage than a somatic cell (Lee et al., 2010b). From transfer of 523 two-cell stage
embryos into five recipients, 1 stillborn and 4 viable piglets were delivered from 2 pregnancies. This
study showed that this cell type can be used as donor cell for producing piglets that cannot be easily
cloned from differentiated cloned cells.

Although the results from these kinds of studies are most valuable for understanding the initial steps of
the cloning process and the epigenetic reprogramming as well as improving the cloning efficiency,
they are of limited value for risk assessment of animal clones themselves and of products like meat
and milk from animal clones.

3.2. Aberrant gene expression in placenta


In mouse and humans PHLDA2 is a gene expressed from the maternal allele which acts to limit
placental growth. A reduced expression of the cattle gene PHLDA2 in SCNT placentas is associated
with pathological overgrowth of the placenta after cloning (Guillomot et al., 2010). However in the
same study, reduced expression was also found in the placenta from clones which developed normally
until term, indicating that some degree of dysregulation took place. This study also confirmed other
studies showing that placentomes from apparently non-pathological clones were over the normal
weight range (see EFSA 2009, EFSA 2008).

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Update on Animal Cloning 2010

Aberrant gene expression has been reported in the bovine placenta, in a study that analysed placenta
from three clones that died immediately after birth (Kim et al., 2009a). In this study placentas from
artificial insemination were used as controls instead of placentas from live born clones.

The incidence of hydrops in the cattle surrogate dam is cell-line dependent and may range from 0 to
100 % with a mean of about 25 % (IETS Manual 4th Edition 2010). When hydrops is suspected, early
termination of the pregnancy is recommended.

A study reported that calves that died immediately after birth, or were killed for humane reasons due
to complications in the perinatal period, have significant variations in the methylation status of the
differentially methylated region (DMR) of the genome, mostly tending towards hypomethylation in
the liver and placenta (Curchoe et al., 2009). This finding is contrary to the global hypermethylation
usually observed in clone embryos. Abnormal expression patterns of imprinted genes (preferential
expression of one parental allele) have been correlated to their DNA methylation patterns.

Aberrant expression and methylation status of imprinted genes have been observed in the pig placenta
(Wei et al., 2010). This study found that the expression of four imprinted genes (IGF2, H19, PEG3
and GRB10) was significantly reduced in placentaes of dead clones compared with placentaes of live
piglets and controls. However, the transcript levels of the genes in the dead piglet clones were normal.
The transcript levels of the genes in live clones rarely differed from those of controls in both piglets
and placentas. This study found that the aberrant expression and methylation of imprinted genes exists
in the placentas rather than in the piglets. This indicates that the expression and methylation of
imprinted genes in the placenta is associated with the foetal developmental potential of pig clones and
that the placenta is especially vulnerable to abnormal gene imprinting.

A study in piglets observed an incidence of 13.9 % (9/65) of umbilical chord malformation (Park et
al., 2009). The effects of this observed malformation include placental insufficiency, foetal
abnormalities and mortality, foetal malformations, preterm birth and low birth weight. However, these
observations have not always been reported in other studies and the underlying mechanisms of these
effects are still not known. In this study an unusually high number of embryos per recipient (calculated
to be about 230 embryos per recipient) were transferred compared with other reports in which
generally about 100 embryos per recipient have been transferred.

3.3. Surrogate dam and uterine function


The expression of three important uterine secretory proteins (i.e. retinol binding protein, osteopontin
and fibroblast growth factor) involved in implantation and maintenance of pregnancy in pigs have
been investigated (Kim et al., 2009b). The maternal uterine genes in pigs were aberrantly expressed to
varying degrees depending on the normality of the developing clone embryos. A uterus with aberrant
gene expression is not fully competent to provide for the developing clone embryo, resulting in
decreased foetal size or even embryo or foetal loss (Kim et al., 2009b). In the same way, recent work
in cattle (mentioned also in the EFSA 2009 statement) demonstrated that uterine gene expression in
the endometrium is influenced by the type of embryo transferred (in vitro fertilised or clone embryo)
into the recipient uterus (Bauersachs et al., 2009; Mansouri-Attia et al., 2009).

3.4. Cattle clones


Calf clones have been reported to have a delayed maturation of skeletal muscle during their first year.
However, after 12 months of age no significant differences were observed between clones and control
animals (Jurie et al., 2009). The foetal origin of this delay has been further studied by investigating
myogenesis of eight clone foetuses. The clone foetuses had a significantly lower number of myotubes
at day 60 of pregnancy compared with controls and a retarded pattern of myosin isoforms by day 260
of pregnancy indicating that disturbances in myogenesis occur early in the foetal life (Cassar-Malek et
al., 2010b).

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Update on Animal Cloning 2010

To investigate DNA methylation, 5-methyldcytosine (5mC) levels in leukocyte DNA of 38 healthy


female bovine clones, representing in total 9 genotypes (5 Simmental and 4 Holstein breeds) have
been measured (de Montera et al., 2010). The absolute deviation in 5mC values of individual clones
from the means of their genotype showed a five fold increase in comparison with normal twins. This
study also revealed DNA methylation variability and DNA hypermethylation in most of the clones,
suggesting that healthy adult clones should be considered as epigenome variants. It is suggested that
DNA hypermethylation might be maintained from the embryonic and foetal stages into adulthood.

DNA methylation patterns have been investigated in the sperm of SCNT bulls (Couldrey et al., 2009).
The results indicate that gametes from bull clones have different epigenotypes from the donor somatic
cells and are similar to artificial insemination (AI) derived bulls. This suggests that any epigenetic
aberrations that bull clones may harbour are unlikely to be passed on to their offspring through their
gametes.

Variations in haematological profiles were analysed between 47 clones and 23 controls from birth
until 15 months of age in New Zealand (Green et al., 2009). Although most parameters were within
the normal range over time (mean values for erytroid, myeloid and lymphoid parameters), cattle clones
commonly displayed altered parameters.

Behaviour studies of adult cattle clones, mixed with conventional heifers, indicated that clones have
similar cognitive capacities of kin and non kin discrimination as control conventional cows (Coulon et
al., in press).

4. Food safety of products from clones


Meat from cattle clones has been incorporated at 5 % and 10 % into diets fed to rats (2 week duration
for females, and 4 week duration for males) and compared with diets with normal meat or without
meat (Hwang et al., 2009). The daily food consumption in both of the meat groups (clone and normal
meat) were significantly lower compared with the control. This study used reproductive physiological
measures and no obvious negative effects were seen in rats fed meat from clones compared with
feeding conventional meat.

Another study from the same group studied the effects on reproductive parameters in rabbits fed a diet
with meat from cattle clones during gestation (up to 27 days) (Lee et al., 2010a). No obvious
differences in reproductive parameters were observed in pregnant rabbits fed meat from clones
compared to control. However, it should be noted that rabbits are herbivores and may not be a suitable
model for assessing a meat diet.

5. Offspring of clones
Information on clone offspring (F1) remains limited especially in cattle with long generation interval.
A study of the characteristics of 39 cattle clone offspring compared to clones and AI controls born and
raised in the same experimental farm, confirmed that none of the F1 calves presented any of the
pathologies observed in clones. They develop similarly to AI controls and differed from the clones
themselves (Heyman et al., 2009). Oxidative and contractile characteristics of muscles have been
investigated by repeated biopsies from 10 heifers born from AI of clones collected at 8, 12 and 18
months of age and compared with 8 AI controls and 9 clones (Cassar-Malek et al., 2010a). The
proportion of slow oxidative isoforms and fast glycolytic isoforms were not significantly different
from the AI controls.

No new information has been identified in relation to the impact of cloning on offspring from pig
clones. Transgenerational studies in farm animals as well as long term behavioural studies have not
been identified.

EFSA Journal 2010:8(9):1784 10


Update on Animal Cloning 2010

6. Breeding and cloning efficiency


This section contains information outside the terms of reference and is provided based on discussion
with the Commission services. In this sense, this section is not an update since the 2009 statement or
2008 opinion and includes information published over several years.

Measurement of cloning efficiency and comparison of cloning with other breeding technologies is
complex and several possibilities exist. Cloning efficiency can be measured as:

- the proportion of embryo clones transferred into surrogate dams that survive into adulthood
(Oback, 2009)

- the ratio of the number of healthy calves born to the number of embryos transferred (Zhou et
al., 2009).

These descriptions do not consider the initial fusion between oocytes and donor cells where the
structure formed may not develop into an embryo suitable for transfer to a surrogate dam. This has
been referred to as the in vitro development rate calculated as the number of transferable blastocysts
per 100 cultured reconstructs (Zhou et al., 2009).

It should be recognised that with conventional breeding a significant proportion of oocytes fertilised
by sperm will not develop into a viable embryo and give rise to a live offspring. However, it should be
noted that the information related to efficiencies of conventional breeding is not the focus of this
statement and the information presented below is a reflection of only a few publications, mostly
focusing on cattle.

6.1. Efficiency of ART other than cloning


As cloning is an asexual technology no natural comparator exists, but several assisted reproductive
technologies (ART) are established for use in animal breeding which can be used. Breeding
technologies such as in vitro fertilisation (IVF), embryo transfer and embryo splitting have an in vitro
handling step which therefore could be used as indirect comparators. It is acknowledged that ARTs are
currently widely used in the zootechnical practice without any underlying formal risk assessment, and
some, like artificial insemination have been used commercially since the 1930’s (Foote, 2002).

In Europe artificial insemination (AI) is used in about 60 % of breedable cows (Thibier and Wagner,
2002), and in pigs ranging from 25 % to over 95 % (e.g. the Netherlands and many north western
European countries (Dominguez et al., 2009; Feitsma, 2009; Wahner and Geyer, 2007)); worldwide
the figures are 42 % and 50 % respectively (Wahner and Geyer, 2007; FAO, 2007). In some European
countries AI is used for the majority of cattle breeding (up to 90 %). The global conception rates
following AI average 50-65 % in cattle and 70-80 % in pigs.

Fertilization rates by artificial insemination in heifers and moderate yielding dairy cows have been
estimated to be 90 % and average calving rates of about 55 %, indicating an overall embryonic and
foetal mortality rate of about 40 % (Sreenan et al., 2001). Another study of AI of cattle (in the
Holstein Friesian breed) a fertilisation failure of 10 %, early embryonic mortality rate of 43 % and late
embryo mortality of 7 % have been reported leading up to a calving rate of 40 % (Diskin and Morris,
2008; Diskin et al., 2006). For pigs, the IFIP (Institut du porc) in France reports a fertility rate of 89 %
at the first heat (IFIP, 2008).

Intracytoplasmic sperm injection (ICSI) has been used as a reproduction technology for research
purposes in farm animals, but to a limited extent (See review (Garcia-Rosello et al., 2009). This
technology has a low efficiency with birth rates ranging from 5.2 % to 50 % in various species.

EFSA Journal 2010:8(9):1784 11


Update on Animal Cloning 2010

By using ART with in vitro produced (IVP) bovine embryos, approximately 30 % to 50 % of embryos
transferred develop into healthy calves at weaning (Alexopoulos and French, 2009; Smeaton et al.,
2003).

6.2. Efficiency of cattle cloning


The typical cloning efficiency in cattle is 8-10 % (Oback, 2009). However, higher efficiencies are
regularly reported, likely as a result of increased knowledge. The majority of losses in cattle clones are
observed in the first 60 days following the embryo transfer, usually without recipient loss and/or
without reported welfare implications.

In Japan 575 cattle clones have been produced as of September 30, 2009 (Watanabe, 2010). Among
the 575 clones 13.9 % (80) were reported to be stillbirths, 13.6 % (94) died within a day and 25.4 %
(146) died due to various diseases and 1.6 % (9) died due to accidents. This corresponds to a survival
rate of 43 % of the born clones. A calving rate for some donor cell lines up to 60 % and even 90 % (a
small study, foetal fibroblast cells as donors, 10 embryos transferred to 10 recipients delivering 9 live
calves, where one died after a few days) have been reported (Urakawa et al., 2004; Zhou et al., 2009).
The efficiency of chromatin transfer of two embryos per surrogate dam is up to 20 % live calves one
month after birth which is related to the donor cell line used (McLean et al., 2010).

Unpublished information from the French research group at INRA (Institut National de la Recherché
Agronomique) indicate that of 90 calves born at term, 79 (87.7 %) were live at birth, 61 (67.8 %) were
live after 3 months and 67 (63.3 %) were live adults. This survival rate (63.3 %) is higher than the one
reported from Japan (43 %).

Perinatal mortality of cattle clones is greater, and survival to weaning (varying up to 75 %) is reduced
compared with conventional breeding (survival > 90 %) (IETS Manual 4th Edition 2010). Long term
effects such as metabolic disturbances would be expected in ageing animal clones from pregnancies
involving abnormal placental development and abnormal in utero environment as this has been
reported in other species, including humans (IETS Manual 4th Edition 2010).

6.3. Efficiency of pig cloning


For a successful recognition of pregnancy in sows, including natural breeding, at least four viable
embryos need to be recognised and implanted to the uterine wall around day 14 post fertilization. To
compensate for the low in vitro developmental capacity of pig clone embryos, a large number of clone
embryos are usually transferred. The most suitable number of embryos to be transferred to recipients is
unknown. This should be considered in the interpretation of cloning efficiencies in pig.

In pigs, the efficiencies of in vitro fertilisation and cloning are similar, when comparing the number of
transferred embryos per recipient (around 100), pregnancy rates (50 % to 100 %) and the number of
piglets born per litter (around 6) (See Table 1). Fewer than 100 embryo clones are compatible with
litter sizes of five or more born piglets (Petersen et al., 2008).

Five surrogate recipients received each about 120 clone embryos, and three pregnancies went to term
resulting in 23 piglets. This corresponds to 3.8 % efficiency (Lee 2010). In a study where pre-
adipocytes where used as donor cells followed by cell cycle synchronisation the transfer of 555
embryos to four recipients, three became pregnant and delivered 13 live-born piglets, corresponding to
an efficiency of 1.9 % (Tomii et al., 2009). In a study using histone deacetylase inhibitor and ear
fibroblast as donor cells, 143 and 125 embryos respectively, were transferred into two recipients and
10 piglets were born corresponding to 3.7 % efficiency (Zhao et al., 2010).

EFSA Journal 2010:8(9):1784 12


Update on Animal Cloning 2010

Table 1: Efficiency of cloning pigs compared with in vitro fertilisation

% Efficiency
No. Pregnant to Number of
(born
Methods embryos/recipient term piglets
piglets/embryos
s (avg) (%) born/litter
transferred)
SCNT
(Walker et al.,
59-128 (102) 80 7 6.9
2002)
(Petersen et al.,
80-162 (128) 75 5.2 4.0
2008)(a)
(Estrada et al.,
ND(c) ND(c) 6.2 ND(c)
2007)
(Schmidt et al.,
40-60 36 4.4 ND(c)
2009)
IVF
(Beebe et al.,
24-35 (b) 67 5.3 11
2009)
(Kikuchi et al.,
66-100 (89) 67 4.25 4.25
1999)
(Yoshioka et al.,
20-25 (23) (b) 100 5.3 24
2003)
(Kikuchi et al.,
50(b) 100 6.3 9
2002)
(a): Transgenic study
(b): IVF embryos are usually transferred after 5-6 days of in vitro embryo culture. Blastocyst
development rate is typically ranging from 15 to 30 % (avg. 25 %); therefore 100 Day 1 embryos
would be equivalent to 25 Day 5-6 embryos. The embryos in the studies were transferred on around
day 5-6. Consequently, the numbers of embryos transferred in the SCNT and IVF studies are
similar.
(c): Not determined

6.4. Conclusion on cloning efficiency


Cloning efficiency in cattle (currently around 10 %) and pigs (currently around 6 %) is lower than by
natural breeding (cattle calving rate 40-55 %) as well as from assisted reproductive technologies
(ARTs), such as artificial insemination. However, compared with in vitro produced embryos and
embryo transfer in pigs, cloning has similar efficiency (~ 6 %).

CONCLUSIONS
Based on the literature search and information provided in the framework of the present statement, it is
concluded that there is still limited information available on species other than cattle and pigs which
would allow for assessment of food safety and animal health and welfare aspects.

Cloning efficiency in cattle (currently around 10 %) and pigs (currently around 6 %) is lower than by
natural breeding (cattle calving rate 40-55 %) as well as from assisted reproductive technologies
(ARTs), such as artificial insemination. However, compared with in vitro produced embryos and
embryo transfer in pigs, cloning has similar efficiency (~ 6 %).

In vitro fertilisation technologies can deliver healthy animals using similar in vitro handling steps (e.g.
maturation, culture) to those used in cloning, but at a higher rate, especially in cattle. This suggests
that the reprogramming of the somatic donor cell nucleus (epigenetic dysregulation) is a major factor
affecting cloning efficiency. If the success rate of the epigenetic reprogramming is improved it is

EFSA Journal 2010:8(9):1784 13


Update on Animal Cloning 2010

expected that the pathologies and mortalities observed in a proportion of clones would decrease
(EFSA 2009).

No new information has become available, since the EFSA 2009 statement and the EFSA 2008
scientific opinion that would lead, at this point in time, to a reconsideration of the conclusions and
recommendations related to the food safety, animal health and welfare aspects of animal cloning as
considered in the 2008 scientific opinion and the EFSA 2009 statement.

EFSA Journal 2010:8(9):1784 14


Update on Animal Cloning 2010

DOCUMENTATION PROVIDED TO EFSA


During the call for data, published the EFSA website from 9 June to 9 July 2010 the following
information, some unpublished, was received:

1. Compassion in World Farming. Farm Animal Cloning, A compassion in World Farming Report -
2010. 56 pages. The submission also contained 5 publications.

2. Individual scientist based in France. 6 publications.

3. Individual scientist based in Ireland. Scientific paper under preparation. 18 pages.

4. Individual scientist based in Italy. E-mail. 2 pages.

5. Individual scientist based in Japan. 4 publications. 1 presentation.

6. Individual scientist based in Turkey. Cloning of Anatolian native cows. Abstract 3 pages.

7. Individual scientist based in Turkey. 1 publication.

8. Individual scientist based in USA. 1 publication.

9. ViaGen Inc USA. 3 reports. Other assisted reproductive technologies. 10 pages. SCNT in pigs.3
pages. SCNT (in cattle). 7 pages. The submission also contained 29 publications.

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Pugliese M, Young S, Lagioia J, Garnil C, Forte Pontes JE, Ereno Junio JC, Mower S and Medina
M, 2007. How healthy are clones and their progeny: 5 years of field experience. Theriogenology,
67, 142-151.
Park JY, Kim JH, Choi YJ, Hwang KC, Cho SK, Park HH, Paik SS, Kim T, Park C, Lee HT, Seo HG,
Park SB, Hwang S and Kim JH, 2009. Comparative proteomic analysis of malformed umbilical
cords from somatic cell nuclear transfer-derived piglets: implications for early postnatal death. Bmc
Genomics, 10,
Petersen B, Lucas-Hahn A, Oropeza M, Hornen N, Lemme E, Hassel P, Queisser AL and Niemann H,
2008. Development and validation of a highly efficient protocol of porcine somatic cloning using
preovulatory embryo transfer in peripubertal gilts. Cloning Stem Cells, 10, 355-362.
Rodriguez-Osorio N, Wang ZD, Kasinathan P, Page GP, Robl JM and Memili E, 2009.
Transcriptional reprogramming of gene expression in bovine somatic cell chromatin transfer
embryos. Bmc Genomics, 10, (24 May 2009).

EFSA Journal 2010:8(9):1784 17


Update on Animal Cloning 2010

Rosenfeld CS, 2009. Animal Models to Study Environmental Epigenetics. Biology of Reproduction,
82, 473-488.
Schmidt M, Kragh PM, Li J, Lin Y, Vajta G and Callesen H, 2009. 78 Establishment of pregnancies in
large white sow recipients after transfer of cloned embryos of different pig breeds. Reproduction,
Fertility and Development, 22, 197-198.
Smeaton DC, McGowan LT, Scott ML, Tervit HR and Cameron CA, 2003. Survival of in vitro-
produced cattle embryos from embryo transfer to weaning. New Zealand Society of Animal
Production, 57-60.
Sreenan JM, Diskin MG and D.G. M, 2001. Embryo survival rate in cattle: amajor limitation to the
achievement of hight fertility. Animal Science, 1 Occasional Publication No. 26, 93-104.
Sullivan EJ, Kasinathan S, Kasinathan P, Robl JM and Collas P, 2004. Cloned calves from chromatin
remodeled in vitro. Biology of Reproduction, 70, 146-153.
Thibier M and Wagner HG, 2002. World statistics for artificial insemination in cattle. Livestock
Production Science, 74, 203-212.
Tomii R, Kurome M, Wako N, Ochiai T, Matsunari H, Kano K and Nagashima H, 2009. Production of
Cloned Pigs by Nuclear Transfer of Preadipocytes Following Cell Cycle Synchronization by
Differentiation Induction. Journal of Reproduction and Development, 55, 121-127.
Urakawa M, Ideta A, Sawada T and Aoyagi Y, 2004. Examination of a modified cell cycle
synchronization method and bovine nuclear transfer using synchronized early G1 phase fibroblast
cells. Theriogenology, 62, 714-728.
Wahner M and Geyer M, 2007. Current aspects of artificial insemination in pigs. Biotechnology in
Animal Hysbandry, 23(5-6), 55-66.
Walker SC, Shin T, Zaunbrecher GM, Romano JE, Johnson GA, Bazer FW and Piedrahita JA, 2002.
A highly efficient method for porcine cloning by nuclear transfer using in vitro-matured oocytes.
Cloning Stem Cells, 4, 105-112.
Watanabe S, 2010. Somatic cell cloned cattle and their risk assessment in Japan. Submitted to EFSA
during the call for data, 1-7.
Wei YC, Zhu J, Huan YJ, Liu ZF, Yang CR, Zhang XM, Mu YS, Xia P and Liu ZH, 2010. Aberrant
Expression and Methylation Status of Putatively Imprinted Genes in Placenta of Cloned Piglets.
Cellular Reprogramming, 12, 213-222.
Yoshioka K, Suzuki C, Itoh S, Kikuchi K, Iwamura S and Rodriguez-Martinez H, 2003. Production of
piglets derived from in vitro-produced blastocysts fertilized and cultured in chemically defined
media: effects of theophylline, adenosine, and cysteine during in vitro fertilization. Biol Reprod,
69, 2092-2099.
Zhao JG, Hao YH, Ross JW, Spate LD, Walters EM, Samuel MS, Rieke A, Murphy CN and Prather
RS, 2010. Histone Deacetylase Inhibitors Improve In Vitro and In Vivo Developmental
Competence of Somatic Cell Nuclear Transfer Porcine Embryos. Cellular Reprogramming, 12, 75-
83.
Zhou WL, Sadeghieh S, Abruzzese R, Uppada S, Meredith J, Ohlrichs C, Broek D and Polejaeva I,
2009. Transcript levels of several epigenome regulatory genes in bovine somatic donor cells are not
correlated with their cloning efficiency. Cloning and Stem Cells, 11, 397-405.

EFSA Journal 2010:8(9):1784 18


Update on Animal Cloning 2010

APPENDIX 1. CONCLUSIONS AND RECOMMENDATIONS FROM THE EFSA 2008 SCIENTIFIC


OPINION
Below are the overall conclusions and recommendations (page 32-33) from the Scientific Opinion of
the Scientific Committee on a request from the European Commission on 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

CONCLUSIONS
Somatic cell nucleus transfer (SCNT) is a relatively new technology in animal reproduction with
limited data available and is increasingly being used in some countries to produce clones. These clones
can then be used for further breeding using conventional or other methods.

While cloning has been applied to several animal species, only in the case of cattle and pigs has there
been sufficient data available to perform a risk assessment.

Uncertainties in the risk assessment arise due to the limited number of studies available, the small
sample sizes investigated and, in general, the absence of a uniform approach that would allow all the
issues relevant to this opinion to be more satisfactorily addressed.

The health and welfare of a significant proportion of clones, mainly within the juvenile period for
bovines and perinatal period for pigs, have been found to be adversely affected, often severely and
with a fatal outcome. Epigenetic dysregulation is considered to be the main source of adverse effects
that may affect clones and result in developmental abnormalities. The use of SCNT in cattle and pigs,
however, has also produced healthy clones and healthy offspring that are similar to their conventional
counterparts based on parameters such as physiological characteristics, demeanour and clinical status.
The production of clinically healthy clones provides evidence in those cases that the epigenetic
reprogramming has taken place successfully.

In relation to food safety, there is no indication that differences exist for meat and milk of clones and
their progeny compared with those from conventionally bred animals. Such a conclusion is based on
the assumption that meat from cattle and pigs is derived from healthy animals as assessed by
mandatory ante-mortem and post-mortem examinations, that milk is produced from healthy cows and
that in both cases these food products are in compliance with food safety criteria regarding
microbiological and chemical contaminants.

No environmental impact is foreseen but there are only limited data available.

RECOMMENDATIONS

General recommendations
ƒ The health and welfare of clones should be monitored during their production life and natural
life span.
ƒ As food animals other than cattle and pig have also been produced via SCNT, risk assessments
should be performed on these species when relevant data become available.
ƒ This opinion should be updated in the light of developments in cloning and/or with new
relevant data.

EFSA Journal 2010:8(9):1784 19


Update on Animal Cloning 2010

Additional recommendations
In relation to epigenetic and genetic aspects of SCNT it is recommended to determine or further
investigate:

ƒ The role of the epigenetic dysregulation as a cause of adverse effects.


ƒ Whether, and if so, to what extent epigenetic dysregulation occurring in clones is transmitted
to the progeny (F1).
ƒ Whether, and if so, to what extent SCNT may induce silent DNA mutations.
ƒ The possible consequences of mitochondrial heterogeneity in SCNT.
ƒ The effects of telomere length in clones derived from different cell sources.
In relation to animal health it is recommended to:

ƒ Conduct further research on the possible effects of SCNT on the natural life span of cattle and
swine clones.
ƒ Investigate further the causes of pathologies and mortality observed in clones during the
gestational and postnatal periods and those observed at a lower frequency in adulthood.
ƒ Further investigate the immunocompetence and the susceptibility of clones and their offspring
to diseases and transmissible agents when reared and kept under conventional husbandry
conditions.
In relation to animal welfare it is recommended to:

ƒ Perform studies on animal welfare, including behavioural studies, in healthy clones under
normal husbandry conditions.
ƒ Monitor the surrogate dams for early markers of abnormal foetal development which could
lead to adverse effects on their welfare.
In relation to food safety it is recommended that:

ƒ Should evidence become available of reduced immunocompetence of clones (see animal


health recommendations above), it should be investigated whether, and if so, to what extent,
consumption of meat and milk derived from clones or their offspring may lead to an increased
human exposure to transmissible agents.
ƒ The database on compositional and nutritional characteristics of edible animal products
derived from clones and their progeny should be extended.

EFSA Journal 2010:8(9):1784 20


Update on Animal Cloning 2010

APPENDIX 2. SUMMARY OF EFSA 2009 STATEMENT


Below is the summary from the Statement of EFSA prepared by the Scientific Committee and
Advisory Forum Unit on Further Advice on the Implications of Animal Cloning (SCNT). The EFSA
Journal (2009) RN 319, 1-15

SUMMARY
The European Food Safety Authority received in March 2009 a request from the European
Commission to expand and further deepen the underlying details related to the recommendations
included in the animal cloning opinion of July 2008 (EFSA Journal (2008) 747, 1-49). The request
was for EFSA to focus in particular on the health and welfare of animal clones and the
recommendations related to investigation of the causes of pathologies and mortality observed in clones
during the gestational and postnatal periods and those observed at a lower frequency in adulthood and
the health and welfare of clones during their productive life and natural life span. In addition the
European Commission requested to know to what extent the current knowledge applies to cloning of
sheep, goats and chicken.

A number of scientific publications have been published since the EFSA 2008 opinion indicating that
Somatic Cell Nuclear Transfer (SCNT) is an active field both regarding basic and applied research.
Most publications have studied embryonic or early development or methodological developments and
there are only a few publications and studies on postnatal or adult animals. If the success rate of the
epigenetic reprogramming is improved it is likely that the pathologies and mortalities observed in a
proportion of clones would decrease.

There is still not sufficient data on species other than cattle and pigs to perform a risk assessment.

This statement confirms that the conclusions and recommendations of the EFSA 2008 opinion are still
valid.

EFSA Journal 2010:8(9):1784 21


EN

EN EN
EUROPEAN COMMISSION

Brussels, 19.10.2010
COM(2010) 585 final

REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT AND


THE COUNCIL

on animal cloning for food production

EN EN
REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT
AND THE COUNCIL

on animal cloning for food production

TABLE OF CONTENTS

1. INTRODUCTION........................................................................................................ 3
2. ANIMAL WELFARE ISSUES.................................................................................... 4
3. ETHICS........................................................................................................................ 5
4. SITUATION IN THE MEMBER STATES................................................................. 6
5. SITUATION IN THIRD COUNTRIES....................................................................... 7
6. PUBLIC PERCEPTION AND STAKEHOLDER OPINIONS ................................... 8
7. TRADE ISSUES .......................................................................................................... 9
8. LEGAL ASPECTS TO BE TAKEN INTO ACOUNT IN THE RISK
MANAGEMENT ....................................................................................................... 10
9. OPTIONS ................................................................................................................... 12
10. CONCLUSIONS........................................................................................................ 14

EN 2 EN
1. INTRODUCTION

This report presents an assessment of cloning technology in relation to food


production. The objective is to examine the relevant aspects of cloning in light of the
current legislative framework.

Cloning1 is a relatively new breeding technique which allows the asexual


reproduction of animals that have shown good productivity, low incidence of disease
and the capacity to cope with the production environment. The scope of the report is
limited to animals when raised for food production. The animal which is obtained
(the clone) is a near exact genetic copy of the original animal. As with any other
breeding technique, it is important to undertake risk assessments on critical aspects in
order to address possible risks as regards food safety and the health and welfare of
animals. This report also examines other aspects, such as the ethical dimension, trade
implications and the consumer's right to be informed about the production process.

An opinion of the European Food Safety Authority (EFSA) adopted on 15 July


20082, cited difficulties in relation to the risk assessment of cloning due to the limited
number of available studies. It also noted that the health and welfare of a significant
proportion of clones had been found to be adversely affected, often severely and with
a fatal outcome. The opinion found no indication of any differences in food safety for
the meat and milk of clones and their progeny compared with conventionally bred
animals. Finally, the opinion did not envisage environmental impacts, but
acknowledged the limited availability of data.

On 26 June 2009, EFSA published a statement on further advice on the use of animal
cloning3. This statement confirmed the validity of the conclusions and
recommendations of the 2008 EFSA opinion, adding that the main source of the
adverse effects that may affect clones and result in developmental abnormalities was
"epigenetic dysregulation"4. Failure of the placental development following cloning
is believed to be one of the reasons why the technique has a low success rate.
Adverse affects, however, vary between species. For example, large offspring
syndrome (LOS) affects cattle but not pigs. This condition can result in difficult birth
and health problems for the surrogate dams and cases of stillbirth. Neither of these
phenomena appears to affect the offspring of clones, born through conventional
breeding techniques.

The EFSA statement of 2009 also noted that if the success rate of the epigenetic
reprogramming were to be improved it is likely that the incidence of pathologies and
mortalities would decrease.

1
For the purposes of this report (and in common with EFSA and EGE Opinions) “cloning” refers to
replication by somatic cell nuclear transfer (SCNT) to create genetic replicas (clones) from adult
animals that share the same nuclear gene set as another organism. This report does not cover embryo
splitting or any form of genetic modification.
2
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902019540.htm
3
http://www.efsa.europa.eu/cs/BlobServer/Statm_of_Efsa/sc_statementej_RN319_en.pdf?ssbinary=true
4
"Epigenetics" seeks to describe the inheritance of information on the basis of gene expression.
Epigenetic changes in reprogramming of the donor’s nucleus in SCNT have been implicated in causing
many of the observed anomalies.

EN 3 EN
Japanese research institutes have been studying animal cloning since 1998. Living
clones and their progeny provide important data allowing analysis of the health and
welfare status of those animals. Between July 1998 and September 2009, 575 cloned
cattle were born in Japan of which 55% died shortly after birth5.

In May 2010, the Commission asked EFSA for a further update of the scientific
assessment of cloning: The EFSA statement of September 2010 indicated that:

"Being a genetic copy of its cell donor, the clone has similar potential productive
performances. It should be stressed that besides quantitative/qualitative traits of
animal products, today’s selection strategies take into account other relevant
parameters, including resistance to the common pathologies (e.g. mastitis, other
infectious and parasitic diseases), fertility, mentality and others related to the
general robustness of the animal. Breeding out such complex traits using the
traditional selection schemes is time consuming and might turn out to be complicated
and the success is not certain. Cloning could contribute to address these issues in a
more rapid manner."

Concerning genetic diversity, the statement indicated that:

"An argument often voiced is that cloning will decrease genetic diversity. However, if
used appropriately, in connection with suitable management measures, cloning is not
expected to adversely affect the genetic diversity among domestic species."

2. ANIMAL WELFARE ISSUES

The available EFSA opinion associates animal welfare problems with the current
state of the application of the cloning technique. Cloning presents severe welfare
challenges for clones arising directly from its use and also through possible
exacerbation of the problems caused by selective breeding.

First of all, as highlighted by EFSA, a large majority of cloned embryos fail to


develop to term and, for those that do, a significant proportion of the animals die
during or shortly after birth, or over the following days and weeks, from
cardiovascular failure, respiratory problems, liver or kidney failure, immuno-
deficiencies or musculoskeletal abnormalities. Significantly, EFSA stresses that: “the
mortality rate of clones is considerably higher than in sexually produced animals”
and that there is “evidence of increased morbidity of clones compared with sexually
produced animals”.

Based on the available data, the overall success rate of the cloning procedure
(measured as the percentage of live clones born from the number of embryos
transferred) is less than 10% in bovine animals and between 5 and 17% in pigs.
Studies undertaken outside Europe have shown that the survival of the progeny of
clones does not differ to any significant extent from the survival of conventionally
bred animals (around 85%).

5
Dr. Shinya Watanabe, National Institute of Livestock and Grassland Science, Japan.

EN 4 EN
In its opinion, EFSA also highlighted important welfare issues for surrogate cattle
dams which suffer from late gestational losses, more difficult delivery (dystocia) and
large offspring. Additional welfare concerns are related to the fact that clones may be
born unusually large and with a range of associated health problems, termed “large
offspring syndrome” (LOS). This is a common problem in cattle and sheep clones,
but not in pigs. It should be noted that some abnormalities may not show up until
later in life. Writing in the OIE Revue Scientifique et Technique a leading cloning
scientist pointed out that the development of musculoskeletal problems, such as
chronic lameness and severely contracted flexor tendons, in these high-production
animals “emphasises the point that any underlying frailties in cloned animals may
not be fully revealed until the animals are stressed in some manner.”6

In order to correctly assess the impact of cloning on the welfare of farm animals, it is
important to consider the ways in which cloning is likely to be used within the
livestock sector. Whilst the cloning of the fastest growing and high yielding animals
may lead to higher proportion of animals suffering from such health and welfare
problems, the cloning of conventionally bred animals, which are resistant to certain
diseases or which can easily adapt to difficult environmental conditions, may have
some possible benefits from a welfare point of view.

3. ETHICS

The European Group on Ethics in Science and New Technologies (EGE) published a
report on the ethical aspects of animal cloning for food production in January 20087.

The EGE expressed doubts on the ethical justification of cloning animals for food
production purposes, "considering the current level of suffering and health problems
of surrogate dams and animal clones". The EGE also concluded that the issue of
ethical justification on the progeny of clones was open to further scientific research
and did "not see convincing arguments to justify the production of food from clones
and their offspring".

The basic ethical issue raised by EGE concerns the moral status that people attribute
to animals. The position of society on this issue has broadly evolved along two lines:
either animals were seen as mere possessions by their owners and available to them
for any purposes that they saw fit, or animals were given respect in varying degrees.
These attitudes were influenced strongly by cultural and religious traditions.

Actions causing pain to moral subjects are considered morally problematic.


Therefore, if cloning or any other breeding or farming technique affects animal
welfare and health, then this use is difficult to accept. Such theories have advocated
the possible use of animals only under specific conditions where animal pain is
minimised and authorised in well-justified circumstances based on the 3Rs
(reduction, refinement and replacement) principle and on the five freedoms as
defined by the Farm Animal Welfare Council (FAWC): freedom from (1) hunger,

6
Wells DN. 2005. Animal cloning: problems and prospects. Revue Scientifique et Technique
(International Office of Epizootics) 24(1):251-64.
7
http://ec.europa.eu/european_group_ethics/activities/docs/opinion23_en.pdf

EN 5 EN
thirst and malnutrition; (2) fear and distress; (3) physical and thermal discomfort; (4)
pain, injury and disease; and (5) freedom to express normal patterns of behaviour.

Another theory defends an even stricter line, advocating that animals have a moral
value in themselves as "subjects-of-life" (intrinsic value argument) and states that
both human and non-human beings are (analogously) moral entities because of their
sentient capacities. The corollary of this argument is not to use animals for human
purposes. Therefore, there is opposition to animal bio-engineering on the basis of
categorical arguments.

Another ethical issue concerns intellectual property rights. Patenting in animal


cloning is so far limited to nuclear transfer techniques.

4. SITUATION IN THE MEMBER STATES

Imports, trade and use of products from clones (food, semen, and embryos) are
covered by general EU legislation. There is no obligation for operators or authorities
to notify the production, trade or import of clones or their semen and embryos so it is
not possible to gain a complete picture of the overall situation. However, for meat
and milk a pre-market authorisation is mandatory, according to the Novel Foods
Regulation8.

Denmark has imposed a national ban on the use of animal cloning for commercial
purposes. Any exemptions to this ban must be approved and must demonstrate a
benefit taking into account the stress or suffering caused, including considerations of
animal integrity, instincts and welfare. At the core of this ban lies the ethical concern
that this might lead to human cloning, hence Denmark is in accordance with the 2005
United Nations Resolution calling on its Member States to "prohibit all forms of
human cloning inasmuch as they are incompatible with human dignity and the
protection of human life".

Apart from Denmark, no other Member State has any specific legislation on the use
of cloning. However, some have provisions in national animal welfare legislation on
breeding and genetic engineering relating to possible pain and suffering of animals
associated with reproduction techniques. In Denmark, the cloning of animals is
permitted only if it serves an essential purpose. Examples of what is considered an
essential purpose are basic research, applied research aimed at improving health and
the environment or creation and breeding of animals producing substances
essentially benefiting health and the environment.

The Commission has received detailed information from some Member States, which
use cloning technology for research purposes only. The United Kingdom reported
three cattle that are the progeny of clones imported as embryos. Germany reported
cloned donor bulls, the semen of which has not yet been used within the EU but has
already been exported to third countries. France reported that since 1998 a total of
90 bovines have been born by cloning at the Institut National de Recherche
Agronomique (INRA). Currently there are 32 living cloned cows. These animals are

8
Regulation (EC) No 258/97 of the European Parliament and of the Council of 27 January 1997
concerning novel foods and novel food ingredients.

EN 6 EN
used only for research purposes and are slaughtered, as are their descendents, as soon
as their research use has ended. Their products are not used as food. In addition,
30 offspring of bovine clones have been born by artificial insemination. Males were
studied until the age of three months and then killed. Females are reared in order to
undertake studies. Currently INRA keeps sixteen young females, offspring from
clones, in the framework of a research programme.

5. SITUATION IN THIRD COUNTRIES

The USA is the most advanced country as regards the cloning of animals for food
production. The situation is also evolving in other countries such as Argentina, Brazil
and Japan. China has expressed interest in the technique and has imported clones
from Australia amongst others. In addition to the Chinese focus on pets, China has
also advocated the use of cloning for the preservation of endangered species.

A voluntary moratorium for the marketing of food products (meat and milk) from
clones is in place in the USA. This moratorium does not, however, cover food from
the offspring of clones nor semen and embryos from clones. Generally there is no
specific labelling or monitoring of semen and embryos from clones and their
offspring. Therefore, it is not possible to substantiate precise figures on the possible
export of semen and embryos to the EU, as clone donors of semen are owned by
farmers, and cloning companies do not have control over their use.

In the USA three major companies sell clones to farmers. Two of the companies put
in place a voluntary tracking system, giving every clone a unique identification (ID).
The system does not however extend to tracking the offspring of clones. The
programme works through the use of a national registry, based on written statements
of truth and incentives. The ID of the clone is entered into a registry that can be
queried and verified by the livestock auction market or packer/processor. The US
companies involved in cloning have contacted the Commission services several
times in order to express their views. The relevant facts can be summarised as
follows:

• Regarding the number of clones, the companies have not provided (for
commercial or confidentiality reasons) precise figures but have often
mentioned "hundreds of pigs" and "thousands of cattle". Therefore products of
offspring of clones have entered the food chain, not only in the US but also in
other parts of the world (not least in Brazil where there are five companies
involved in cloning).

• Regarding traceability, clones are tracked through a registry, plus there is an


economic incentive for farmers not to introduce clones into the food chain.
However, this tracking is not mandatory, so it cannot be guaranteed that milk
from clones does not enter the food chain (even if it is unlikely that such milk
would be used for food purposes). Offspring from clones are not tracked.

In Japan, the National Research Institute assessed the use of cloning technology and
concluded that the government would not take any regulatory measure (such as prior
certification or labelling of imported food from clones and their offspring). However
the current voluntary moratorium on the domestic production of food products from

EN 7 EN
clones and their offspring will be retained. Therefore semen of cloned bulls is
collected and stored but not used for commercial purposes. Argentina reported that
cloning is taking place for commercial purposes. It has no registry for clones. Brazil
reported that cloning is only taking place for research and not food purposes. A draft
text is being discussed in the Brazilian Senate and the Ministry of Agriculture is
expected to present a proposal for the obligatory registration of animal clones in a
national database. Canada requires pre-market approval on a case-by-case basis for
food from clones. The current policy is being reviewed and the Canadian authorities
are awaiting a scientific opinion on food safety and animal welfare, which is
expected by the end of 2010. New Zealand has a moratorium establishing that clones
cannot enter the food chain. In June 2010 the authorities introduced a national
registry scheme for clones. An official traceability system will also apply.

Given the differences of approach with our international partners, there is scope to
further deepen our understanding of the regulatory frameworks and research
parameters that guide cloning outside the EU. To this end the Commission will
strengthen the dialogue with trading partners in order to explore the possibility of
finding common ground for an understanding on cloning.

6. PUBLIC PERCEPTION AND STAKEHOLDER OPINIONS

In 2008 the Commission launched an opinion poll9 (Eurobarometer) to assess public


attitudes towards animal cloning. The study showed that a majority of EU citizens,
whilst having an understanding of the concept of animal cloning, had a broadly
negative perception of its use for food production. Many were concerned about the
lack of information concerning the long-term consequences of cloning and many
cited ethical concerns. There was a general feeling that the cloning of animals for
food production purposes would not benefit the consumer, with few believing that
using cloning for food production would be much more efficient in the long run or
lower the cost of food products for consumers.

However, in contrast to the generally negative perception of cloning, 44% thought


that cloning can be justified under certain circumstances, such as for the
improvement of resistance of animals against diseases or to preserve rare animal
species.

Animal welfare groups have campaigned strongly against the use of cloning for food
production in the EU. These groups claim that animal welfare legislation, provides a
basis for the prohibition of the technique to prevent detrimental effect to the welfare
of the animals. The same animal welfare groups stress the need to apply restrictive
measures to products from the offspring of clones, even if such animals are produced
through conventional breeding techniques. They consider it essential for the
offspring of clones to be included in the EU’s approach to cloning for food.
According to these organisations, a prohibition of the placing on the market of meat
and milk from clones (but not their offspring) would not be enough to restrain the use
of the technique in Europe.

9
European attitudes towards animal cloning: http://ec.europa.eu/public_opinion/flash/fl_238_en.pdf

EN 8 EN
While assessing the situation, the Commission discussed with the EU agri-food
sector the use of cloning, taking into account the interests of the livestock sector with
respect to access to this innovative technology. The Commission discussed with the
Association of European farmers and of European agri-cooperatives (COPA-
COGECA) the possibility of a voluntary moratorium for a limited period of time on
the use of clones and their offspring. The purpose of such a voluntary moratorium
would be to ensure that future regulatory options would not be compromised by the
appearance on the EU market of such animals and animal products. However,
COPA/COGECA10 takes the view that such a moratorium would not be appropriate,
in particular because there are currently no means, nor controls, first to ensure full
traceability of imported products and second to legally pursue those who break the
moratorium.

The European meat processing industry CLITRAVI11 states that products from
cloned animals and/or their offspring thereof are being sold within the EU and that
setting up a traceability system will be very costly.

Both Parliament and Council expect the Commission to work on a separate proposal
on all aspects of cloning. In the Position adopted in March 2010 the Council
extended the Novel Foods pre-market approval to food from the offspring (first
generation) of clones12. The Parliament reiterated, at its July plenary, its request for a
total ban on the cloning of animals; on imports of live clones and their offspring; on
the marketing of food from clones and their offspring; and on the import of semen
and embryos of clones.

7. TRADE ISSUES

Breeding of the European bovine herd takes place mainly through artificial
insemination. This has consequences on trade. Around 2.5% of the bovine semen
used in artificial insemination in the EU is imported, of which approximately 99%
from USA and Canada. According to the data available on TRACES (EU system to
dispatch information set out in veterinary certificates accompanying animal and
animal products traded within the EU and imported from third countries), the overall
number of doses of bovine semen imported from USA and Canada into the EU in
2009 was above 1 200 000. These figures are supported by those for the first
semester of 2010, with more than 600 000 doses of semen imported from these two
countries.

Assuming that 50% of the doses of semen imported have been successfully used to
inseminate cows in the EU in 2009, this means that around 600 000 calves born in
the EU in 2010 are progeny of US or Canadian bulls. This amounts to approximately
2% of the calves born each year in the EU. There is no information about the number
of doses of imported semen coming from cloned bulls.

Imports of embryos for embryo transfer and of breeding animals also take place.
747 consignments of bovine embryos were imported into the EU in 2009.

10
http://www.copa-cogeca.be/Main.aspx?page=search&lang=en
11
http://www.clitravi.eu/
12
Reference COM (2007) 872 of 7 January 2008

EN 9 EN
Imports of live bovines are much less common. In the first semester of 2010 only
24 breeding animals were imported into the EU (from Croatia and Canada)13.

For live animals, animal products (such as semen and embryos but also wool and
leather) and food, the following multilateral agreements of the World Trade
Organisation (WTO) are relevant: the General Agreement on Tariffs and Trade
(GATT), the Agreement on the Application of Sanitary and Phytosanitary Measures
(SPS) and the Agreement on Technical Barriers to Trade (TBT). The precise
determination which of the WTO provisions are relevant would depend (a) on the
justification and (b) on the nature of the legislation to be drafted.

Any measure adopted would have to honour the principle of "National Treatment",
which prohibits less favourable treatment of like products imported (Article III:4
GATT), and the requirement to eliminate quantitative restrictions (Article XI
GATT). Exemptions from these general rules can be justified under Article XX of
GATT (General Exemptions) and/or the TBT or SPS agreement. The two latter
would allow exemptions in line with international standards or based on scientific
evidence. The potentially relevant international standard setting bodies for food
safety (Codex Alimentarius) and animal health (World Organisation for Animal
Health (OIE)) have not set relevant standards on cloning.

There is no scientific evidence which could justify restrictions on food from clones
and food from offspring of clones based on human health concerns. EFSA has
however expressed concerns which are related to the welfare of clones.

The most relevant exemptions from Article III and XI of GATT would thus be the
exception on "public morals" which could include animal welfare (paragraph a
GATT XX) or the protection of life and health. The WTO exemptions are subject to
strict requirements, amongst others, proof of the necessity of the measure to obtain
the objective in question, which implies that it has to be investigated whether there is
not a less trade restrictive way to obtain the same objective, as well as proof of
application in a non-discriminatory, non-arbitrary, non-trade restrictive manner.

8. LEGAL ASPECTS TO BE TAKEN INTO ACOUNT IN THE RISK


MANAGEMENT

Animal Health and Zootechnics

The applicable law, both veterinary and zootechnical, is based on Article 43 of the
Treaty of the Functioning of the European Union. The rules do not distinguish
between animals produced by different reproduction technologies (e.g. artificial
insemination, embryo transfer, embryo splitting, in-vitro-fertilisation or cloning) as
from a genetic perspective none of these practices affects the genome or
susceptibility to infectious diseases.

13
Switzerland is not considered here, as in accordance with an agreement in place on veterinary issue, it is
bound to apply EU legislation. Therefore trade in live animals with Switzerland takes place in
accordance with the rules applying amongst Member States.

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The basic aim of EU animal health legislation is to control infectious diseases. This
legislation harmonises animal health conditions governing EU trade and imports
from third countries. Animals and their products are traded with veterinary
certificates. The certificates do not contain information about the reproduction
technology by which the animal or (for semen, ova and embryos) the donor animal
was produced.

The basic aim of EU zootechnical legislation is to improve livestock performance by


rules to ensure free trade and harmonised conditions for imports of 'pure-bred'
breeding animals and their genetic material. Pure bred breeding animals are traded
with pedigree certificates containing the parentage of the animal. This legislation
does not however affect the trade, imports or breeding of non pure-bred animals
(representing some 95% of pigs, sheep and goats, 90% of beef cattle and 50% of
dairy cattle).

EU zootechnical legislation establishes that pedigree certificates are issued by


approved breeders’ organisations or associations to ensure the ancestry, performance
and genetic value of pure-bred breeding animals (bovine, swine, equine, sheep and
goats) and their semen, ova and embryos that are traded within the EU or imported
from third countries. These certificates do not foresee that information is given if the
animals in question are clones/offspring of clones or if they are conventionally bred.

Animal welfare

Cloning could be examined in the light of the provisions of Council Directive


98/58/EC concerning the protection of animals kept for farming purposes. Paragraph
20 of the Annex to the Directive states that: “Natural or artificial breeding or
breeding procedures which cause or are likely to cause suffering or injury to any of
the animals concerned must not be practised.” The same text is included in the
European Convention for the protection of animals kept for farming purposes, which
gives principles for the keeping, care and housing of animals, in particular in
intensive breeding systems. Member States are responsible for the implementation of
EU legislation on their territory. Furthermore, Article 13 of the Treaty of the
Functioning of the EU clearly states that animals welfare needs must be fully taken
into account when drafting and implementing EU policies on agriculture, fisheries,
transport, internal market, research and development and space.

Traceability of animals

In the EU, food producing animals are subject to traceability requirements which also
apply to clones. Individual traceability has been in place for bovine animals since
1997. For sheep and goats, individual traceability began in 2010. Pigs have been
traceable on a batch basis since 1992. The current rules do not foresee a need to
record on the documents any reference to reproduction technology.

Novel Foods issues

Food from clones is covered by Regulation (EC) 258/97 on Novel foods, since such
food is derived from animals that are obtained by non-traditional breeding
techniques. This means that these food products cannot be put on the market without
a safety assessment and a specific authorising legal act. To date, no application has
been made by any company seeking to put food from clones on the market.

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Legislation on organic farming

Since 1991, the EU has in place a legislative framework relating to the practice of
organic farming. At first the organic Regulation only regulated plant products.
Additional provisions for the production of animal products were later introduced.
These rules included animal feed, prevention of illness, veterinary treatment, animal
protection, livestock breeding in general and the use of livestock manure14.

With regard to breeding, the Regulation states that reproduction shall take place
using natural methods. However artificial insemination is allowed, but any other
form of artificial reproduction, such as cloning and embryo transfer, shall not be
used. The use of inducing treatments with hormones or similar substances is
forbidden, unless in the form of therapeutic treatment for an individual animal.

The EU framework on organic farming provides for the guarantee that food is
obtained from animals bred without the use of any "non-traditional breeding method"
such as cloning or embryo transfer.

9. OPTIONS

The assessment of the situation shows that it is scientifically accepted that there are
no food safety concerns about food produced from clones or their offspring. The
risks for animal welfare are however a solid basis for the Commission to initiate a
legislative process. To address the concern that people perceive the cloning of
animals as morally wrong could be seen as another factor to be taken into account
under EU law.

The options are therefore:

(1) Legal status quo

Cloning would continue not to be specifically regulated at EU level. Clones


and their reproductive materials (semen, ova and embryos) would continue to
be marketed in the EU under the general rules. Food from clones would still be
subject to a pre-market authorisation under the Novel foods Regulation. Food
from the offspring of clones would continue to be covered by generic rules,
which ensure the safety of those products and the functioning of the single
market15.

14
Council Regulation (EC) No 834/2007 of 28 June 2007 on organic production and labelling of organic
products and repealing Regulation (EEC) No 2092/91.
15
Treaty of the Functioning of the EU, Art. 34 – 36, General food law Regulation (EC) No 178/2002 on
the general principles and requirements of food law, Regulation (EC) No 852/2004 on the hygiene of
foodstuffs, Regulation (EC) No 853/2004 on the specific hygiene rules for food of animal origin.

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(2) Total prohibition

• Prohibition of the cloning of farm animals for food production: This


would address the key issue pertaining to cloning, namely the welfare
concerns. Cloning would not be allowed on EU territory for food
production purposes.

• A ban in the EU on the use of clones and of the placing on the market
of food from clones: This measure, which would also apply to imports
would ensure coherence with the ban of the cloning technique in the EU.

• A ban of the placing on the market of offspring of clones and food


from the offspring of clones: This measure would not be justified on
grounds of protecting animal welfare, animal health or public health in so
far as there are no welfare concerns for the offspring of clones as they are
produced by normal reproduction techniques, nor safety concerns for
food derived from offspring of clones, as indicated by EFSA. As food
from the offspring of clones cannot be distinguished from food from
other animals, a complete traceability system would be needed. This
would be extremely burdensome to put in place as it would imply
detailed tracing of all generations of offspring, for the species used for
food production. Furthermore, such prohibition would lead to a ban of
imports of any food of animal origin (meat, milk and processed
products), from third countries which may have imported reproductive
material from clones. A total ban on the import of food from the
offspring of clones would have a considerable and disproportionate
economic impact on EU agriculture production and trade. In addition,
there are no welfare or health or food safety concerns to justify such
action.

• A ban on the use of reproductive material from clones: There are no


health or food safety concerns linked to the use of conventional breeding
techniques, therefore a ban on imports of reproductive material from
clones is difficult to justify.

(3) Mix of measures

The Commission considers that a mix of measures would meet the concerns
raised on the issue of cloning. These measures could include:

• A temporary suspension of the cloning technique of farm animals for


food purposes: This option addresses the welfare issues linked to the use
of the cloning technique for food production in the EU. As the technique
may mature and alleviate partially or fully these concerns, the prohibition
should be revisited after a certain period.

• A temporary suspension of the use of cloned farm animals: This is a


limited measure since imports of live clones are rare and no commercial
cloning occurs in the EU. This would ensure coherence with the
suspension of the cloning technique.

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• A temporary suspension of placing on the market of food from
clones: This suspension which would apply also to imports would ensure
coherence with the ban of the technique in the EU.

• Traceability of reproductive material: This would allow farmers and


the food industry to develop information schemes. In order to distinguish
between (i) semen and embryos from clones and (ii) semen and embryos
originating from conventionally bred-animals it would be necessary to
amend certain certification requirements laid down in the zootechnical
and animal health legislation. As operators would be required to mention
in existing certificates whether or not the reproductive material derives
from a clone, the administrative burden is limited. Such information is
not difficult to retrieve as the genetic value is usually requested by the
purchaser. Further, some trading partners using the cloning technique for
food production purposes have already established - or envisage to do so
- a specific system of compulsory registration of clones, which facilitates
further the traceability of reproductive material.

10. CONCLUSIONS

In view of the issues outlined above, and in particular the need to address the welfare
concerns linked to the use of the cloning technique and the appropriateness to allow
market information, the Commission will propose to:

(i) Suspend temporarily the use of the technique in the EU for the reproduction of
all food producing animals; the use of clones of these animals; and the
marketing of food from clones.

(ii) Establish the traceability of imports of semen and embryos to allow farmers
and industry to set up data bank(s) of offspring in the EU.

With a review clause after 5 years, the proposed legislative measure will be based on
the appropriate legal basis taking into account its content and objective. Cloning
would however remain possible for all other purposes than food production such as
research16, production of pharmaceuticals or the conservation of endangered species
or breeds. During the five year period, the Commission will monitor the scientific
and technological development of cloning in order to asses whether, when and under
which conditions these provisional measures could be removed. No legal measures
are proposed in relation to food from the offspring of clones. However, the
establishment of the traceability system under (ii) above makes information schemes
possible.

16
The use of clones in research must be in compliance with the Directive 86/609/EEC on the protection of
animals used for experimental and other scientific purposes.

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The future scenarios can be summarised as follows:
Clones Offspring

Offspring Food
Clone itself Embryo/semen Food products Embryo/semen
itself products

Produced in Temporary No measure


the EU suspension of
the technique As long as the technique is suspended there will be no products (embryos, semen, food) of clones
for food produced in the EU and of their offspring
production

Imported in Temporary Traceability Temporary No measure


the EU suspension of requirements on suspension of
imports of exporters to EU placing on the
clones market.

The Commission invites the Parliament and the Council to consider the contents and
conclusions of this report and to express their positions in due course.

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