animal cloning for food production (report by u.k. food standards agency)

8/8/2019 Animal Cloning for Food Production (Report by U.K. Food Standards Agency)

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

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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 relationto the cloning of animals for food production.

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

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 FSAs primary objective in responding to this challenge is to ensure that foodsafety is not compromised by any novel food or process. The available evidenceis that food (milk and meat) derived from the progeny of cloned cattle and pigsrepresents no different risk to food safety to that which is from traditionally-bredanimals.

As always, if that evidence changes, the FSAs advice to consumers andgovernment would change as necessary. The Board is keen to maintain a highlevel of scrutiny of the science and evidence as it emerges.

The FSA should not attempt to regulate any process or practice which cannot betraced or measured to an acceptable level of confidence. In this case it would bedisproportionate to try to establish a monitoring process (whose purpose wouldbe to ensure the safest possible food), where there is no discernible risk and withthe knowledge that it would only be feasible for a very small proportion of themarket. In the absence of traceability, the only other option would be a ban whichwould be entirely inappropriate given the current evidence of risk to humanhealth.

The Board will advise agriculture ministers that they should commission theappropriate bodies to investigate further the ethical and welfare concerns thathave been an important feature of consumer concerns. The FSA would be keento be involved in any consumer dialogue.

Legislation should be consistent and harmonised across the EU and anyuncertainties in interpretation should be rapidly resolved.

In the absence of an actual application for authorisation of meat or milk derivedfrom the progeny of cloned cattle, the Board requested that the Executive should


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commission the Advisory Committee on Novel Foods and Processes (ACNFP) toconduct a hypothetical assessment.

2.2 The Chair and Chief Executive have met Defra Ministers (England) and havepresented the Boards conclusions. Devolved Ministers have been informed ofthe Boards conclusions in writing, and made no comments.

3 STRATEGIC AIMS

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

4 DISCUSSION

4.1 The following information has become available since the Boards discussion inSeptember: 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 Boards advice and the

Commissions report and have agreed a UK position on the Commissionsrecommendations.

The ACNFP has considered the available data on milk and meat from clonedanimals and their descendants.

EFSA statement4.2 Following its 2008 review of the implications of the technology, which was

updated in 2009, EFSA received a request from the European Commission inMay 2010 for a further update on scientific developments into the use of animalcloning for food production purposes (FSA10/09/05 para 4.3). The Commissionalso asked whether there were any new data available regarding the health andwelfare of cloned animals.

4.3 On 17 September 2010 EFSA published a further statement ( Annex A ) reportingthat, in terms of food safety, the composition of meat and milk from clonedanimals is no different to that produced by conventionally reared animals,consistent with the conclusions in its original 2008 opinion. EFSA noted thatthere were limited data for species other than cattle and pigs. There were no newdata on the health and welfare of cloned animals for food production that wouldalter its previous conclusions in relation to food safety or animal health andwelfare aspects of animal cloning.


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European Commission report4.4 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 foodchain, citing concerns relating to animal health and welfare, loss of geneticdiversity and risk to the image of European agriculture. In response, Ministersfrom EU Member States requested that the Commission prepare a report on foodproduction from cloned animals (FSA10/09/05 paragraph 4.22).

4.5 The Commissions report ( Annex B ) was published on 19 October and reviewsthe 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 forfood production, the use of clones and the marketing of food from clones in theEU. The report does not recommend any restrictions on the use of the immediateoffspring or later descendants of clones or on the marketing of food obtained fromsuch animals, although it proposes that imports of semen and embryos derivedfrom clones and imported from outside the EU should be identified as such onimport certificates so that farmers and industry can set up traceability systemsthat 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 byMember States

UK Government Position4.8 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 furthernegotiations and discussions in Brussels, taking account of food safety andconsumer choice, as well as animal welfare, implications for international tradeand ethical considerations.

4.9 The Governments general view is that all regulation should be proportionate andenforceable, safeguarding the principles of food safety and consumer choice andguided by the principles of better regulation and evidence-based decision-making. It recognises that cloning is not a traditional breeding technique and, assuch, accepts that, under the EU Novel Foods Regulation 258/97, approvalshould be sought before food from clones themselves can be marketed.

4.10 The Government recognises that cloning is a relatively new technique and thatthe 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 suspensionon cloning, the use of cloned animals and the marketing of food from clonedanimals would be disproportionate in terms of food safety and animal welfare.The UK therefore does not support the Commissions recommendations for thetemporary suspension of animal cloning for food production because insufficientevidence has been provided to justify a ban. The Government would need to seean impact assessment that demonstrated the need for and benefit of newregulation. However, the Government considers that controls should not apply toimmediate offspring of cloned animals or to later generations, where these areconceived by traditional breeding techniques.

4.12 The Government also questions the value of the proposed traceability system forimported semen and embryos from cloned animals, as this would not deal either

with offspring of clones already present within the EU or with imported foodderived from animals with clones in their ancestry.

ACNFP discussion4.13 At the 15 September meeting Board Members noted that no applications for the

approval of food from cloned animals (or their descendants) have been madeunder the EU regulation on novel foods, and asked that the ACNFP beapproached to conduct a hypothetical assessment.

4.14 At their meeting on 25 November, held in open session, the ACNFP reviewed theavailable data, presented in the style of a novel food application. The discussionpaper is published on the ACNFPs website and the meeting was attended byobservers from the general public and by the Agencys Chief Scientist. TheCommittee concluded that:

the evidence showed no differences in composition between the meat and milkof conventional animals, clones or their progeny, which is therefore unlikely topresent 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 differentenvironments may affect the meat and milk.

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

consumers may want to see effective labelling of products from clones and theiroffspring.

4.15 The draft minutes of the Committees 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 Agencys interpretation has been that foodobtained from offspring and later descendants of cloned animals falls within thescope of novel foods. Others including the European Commission take anarrower view and consider that the regulation applies only to cloned animalsthemselves, so that food from descendants of clones can be freely marketedwithout the need for assessment and authorisation.

5.2 The Agency is continuing to review the legal issues associated with this point ofinterpretation of the current regulation, in consultation with other GovernmentDepartments. In the meantime the Agencys interpretation is unchanged.

6 CONCLUSION AND RECOMMENDATION

6.1 The Board is invited to consider the new information that has become availablesince 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 thereare no food safety grounds for regulating foods from the descendants ofclones?

Subject to legal opinion, should the FSA now adopt the stance taken bythe European Commission and others, that food obtained from thedescendants of clones does not require authorisation under the novelfoods regulation?

Does the Board wish to press the European Commission for formalclarification on the relative status of food from clones and theirdescendants 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 wouldbe unnecessary and disproportionate, providing no significant consumerbenefit?

Does the Board wish to ask Defra and its devolved equivalents to considerwhat information about animal cloning should be provided to the publicabout ethics and welfare?

For further information contact Sandy Lawrie on 020 7276 8565, [email protected]


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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

1 European Food Safety Authority, 2010

STATEMENT OF EFSA

Update on the state of play of animal cloning 1

European Food Safety Authority 2, 3

European Food Safety Authority (EFSA), Parma, Italy

ABSTRACT

The European Food Safety Authority (EFSA) received in May 2010, a request from the European Commissionfor 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 2008scientific 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 animalcloning and a peer review by external experts. Based on the literature search and information provided, it isconcluded that there is still limited information available on species other than cattle and pigs which wouldallow for assessment of food safety and animal health and welfare aspects. Cloning efficiency in cattle (currentlyaround 10 %) and pigs (currently around 6 %) is lower than by natural breeding (cattle calving rate 40-55 %) aswell as from assisted reproductive technologies (ART), such as artificial insemination. However, compared within vitro produced embryos and embryo transfer in pigs, cloning has similar efficiency (~ 6 %). No newinformation has become available, since the EFSA 2009 statement and the EFSA 2008 scientific opinion thatwould lead, at this point in time, to a reconsideration of the conclusions and recommendations related to the foodsafety, animal health and welfare aspects of animal cloning as considered in the 2008 scientific opinion and theEFSA 2009 statement. European Food Safety Authority, 2010

K EY 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 14-09-20102 Correspondence: [email protected] 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 Journal2010:8(9):1784. [21pp.] doi:10.2903/j.efsa.2010.1784. Available online:www.efsa.europa.eu/efsajournal.htm


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Update on Animal Cloning 2010

2EFSA Journal 2010:8(9):1784

SUMMARY

The European Food Safety Authority (EFSA) received in May 2010, a request from the EuropeanCommission 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 datafrom European research centres about the health and welfare of clones during their production life andnatural life span.

The present statement follows the EFSA 2009 statement and EFSA 2008 scientific opinion and isbased on a review of identified peer reviewed scientific literature up to 1 July 2010, information madeavailable to EFSA following a call for data, discussion with experts in the field of animal cloning anda peer review by external experts. The focus of the statement has been to evaluate information relatedto 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 themain source of adverse effects that may affect clones and result in developmental abnormalities. Thehealth and welfare of a significant proportion of clones, mainly within the juvenile period for bovinesand perinatal period for pigs, have been found to be adversely affected, often severely and with a fataloutcome. The use of cloning by SCNT (Somatic Cell Nuclear Transfer) in cattle and pigs, has alsoproduced healthy clones and healthy offspring that are similar to their conventional counterparts basedon parameters such as physiological characteristics, demeanour and clinical status. In relation to foodsafety, there is no indication that differences exist for meat and milk of clones and their progenycompared with those from conventionally bred animals. The EFSA 2009 statement confirmed that theconclusions 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 isconcluded that there is still limited information available on species other than cattle and pigs whichwould allow for assessment of food safety and animal health and welfare aspects.

Information, published over several years, indicate that cloning efficiency in cattle (currently around10 %) 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 suggeststhat the reprogramming of the somatic donor cell nucleus (epigenetic dysregulation) is a major factoraffecting cloning efficiency. If the success rate of the epigenetic reprogramming is improved it isexpected 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 2008scientific opinion that would lead, at this point in time, to a reconsideration of the conclusions andrecommendations related to the food safety, animal health and welfare aspects of animal cloning asconsidered in the 2008 scientific opinion and the EFSA 2009 statement.


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T ABLE 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


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R EQUEST AS PROVIDED BY E UROPEAN C OMMISSION

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

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

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

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

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

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

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

[Signed]


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E VALUATION

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 EuropeanCommission 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 Europeanresearch centres about the health and welfare of clones during their production life and natural lifespan. The present statement follows the EFSA 2009 statement and EFSA 2008 scientific opinion andis based on a review of identified peer-reviewed scientific literature up to 1 July 2010 and additionalinformation 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 andwelfare 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 inthe statement.

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

1.1. EFSA scientific opinion of 2008 and EFSA statement of 2009This statement builds on the previous Scientific Opinion of the Scientific Committee on a request fromthe 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 andProducts 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 theImplications of Animal Cloning (SCNT) issued in June 2009 (EFSA, 2009). The conclusions andrecommendations of the 2008 scientific opinion and the summary of the 2009 statement are found inappendices 1 and 2.

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

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


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concluded on 1 st July 2010. The search aimed at identifying publications in publicly availabledatabases, mainly Pubmed, ScienceDirect and ISI Web of Knowledge. The literature search includedsome 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 retrievedinformation in general excluded several types of studies; transgenic animals, inter-species cloning,studies focusing on methodological developments and improvements and studies involving non-farmanimals such as rats and mice. Studies where no live-born animals were reported were in general notconsidered 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 onunderstanding 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 aimsat clarifying the underlying biological mechanisms and is not necessarily focused on producing liveanimal clones. Academic research aims also at improving cloning protocols to increase the cloningefficiency as well as attempts to clone species that have not been cloned before. As cloning research isresource intensive, samples and replications are often small and the keeping of live animals for longperiods is not always economically feasible. Private companies involved in research mainly aim atimproving efficiency of the cloning technology, but it should be noted that private research andmethod development is unlikely to be published in detail in view of the proprietary nature of the dataand confidential business information.

Identifying and clarifying the underlying mechanisms involved in cloning is a complex task and thealterations 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 culturesystem, embryo stage, surrogate dam preparation and operators skills. The failures observed incloning can be traced to epigenetic alterations, specifically failures in chromatin remodelling and DNAand histone methylation (EFSA 2008 and 2009).

The number of born somatic cell cloned animals has increased worldwide into the thousands and thetechnique 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 areworking 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, farmanimal 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 andoutput, i.e. the number of laboratories involved and their publications, cattle are the most importantcloned livestock species (Oback, 2009).

2.1. Applications of cloning

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


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2.1.1. Breeding elite animals

Being a genetic copy of its cell donor, the clone has similar potential productive performances. Itshould be stressed that besides quantitative/qualitative traits of animal products like milk volume orlean meat, todays selection strategies take into account other relevant parameters, including resistanceto the common pathologies (e.g. mastitis, other infectious and parasitic diseases), fertility, mentalityand others related to the general robustness of the animal (e.g. lameness). Breeding out such complextraits using the traditional selection schemes is time consuming and might turn out to be complicatedand 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 pharmaceuticalsubstances. 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 usedappropriately, in connection with suitable management measures, cloning is not expected to adverselyaffect the genetic diversity among domestic species (EFSA 2008). It is appropriate to recall that thelast century has seen a dramatic reduction of animal species, mostly large mammals, mainly caused byhuman-related activities. The obvious consequence of such phenomenon is the progressive contractionin biodiversity. Paradoxically, this problem does not involve wild species only, but also domesticones, often local breeds perfectly adapted to particular ecotypes, being substituted by a few moreproductive 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 fora risk assessment. There are, for example, no identified compositional analyses of meat other thanfrom cattle and pigs. It is currently impossible to prevent the development of all pathologies associatedwith clone pregnancies, which does not mean that all clone pregnancies result in pathologies of thenewborns (IETS Manual 4 th 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 suggeststhat the reprogramming of the somatic donor cell nucleus (epigenetic dysregulation) is a major factoraffecting cloning efficiency. If the success rate of the epigenetic reprogramming is improved it isexpected 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 variousaspects of the initial steps in the cloning process. They investigate biological mechanisms andoptimisation of oocyte and donor cell preparation, cellular transfer procedures and the in vitro embryoculture 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 reproductivetechnologies (ART) and with conventional breeding. Many of these studies are designed to investigate


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only the in vitro stage. The in vivo stage, i.e. after embryo transfer to a surrogate dam, is usually notconsidered. 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 basedcommercial cloning company, has submitted unpublished information indicating that there is a widevariability between cell lines, where certain cell lines exhibit much higher cattle calving rate and day60 healthy calf rate, compared with the average of other cell lines used by ViaGen (Figure 1). Thisconfirms previous data published by Panarace (Panarace et al., 2007).

Figure 1: Cell line variability and calving rateEight percent of ViaGen cell lines (18/220) have produced 20 % to 40 % live calves at day 60. Unpublished informationfrom ViaGen Inc, USA.

Cloned piglets have been produced from pig bone marrow-derived mesenchymal stem cells, a morepluripotent cell stage than a somatic cell (Lee et al., 2010b). From transfer of 523 two-cell stageembryos into five recipients, 1 stillborn and 4 viable piglets were delivered from 2 pregnancies. Thisstudy showed that this cell type can be used as donor cell for producing piglets that cannot be easilycloned 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 meatand 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 limitplacental growth. A reduced expression of the cattle gene PHLDA2 in SCNT placentas is associatedwith pathological overgrowth of the placenta after cloning (Guillomot et al., 2010). However in thesame study, reduced expression was also found in the placenta from clones which developed normallyuntil term, indicating that some degree of dysregulation took place. This study also confirmed otherstudies showing that placentomes from apparently non-pathological clones were over the normalweight range (see EFSA 2009, EFSA 2008).

Gestation days days of live calves

% o

f l i v e c a

l v e s


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Aberrant gene expression has been reported in the bovine placenta, in a study that analysed placentafrom three clones that died immediately after birth (Kim et al., 2009a). In this study placentas fromartificial 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, earlytermination of the pregnancy is recommended.

A study reported that calves that died immediately after birth, or were killed for humane reasons dueto complications in the perinatal period, have significant variations in the methylation status of thedifferentially methylated region (DMR) of the genome, mostly tending towards hypomethylation inthe liver and placenta (Curchoe et al., 2009). This finding is contrary to the global hypermethylationusually observed in clone embryos. Abnormal expression patterns of imprinted genes (preferentialexpression 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 livepiglets 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 pigletsand placentas. This study found that the aberrant expression and methylation of imprinted genes existsin 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 andthat 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 etal., 2009). The effects of this observed malformation include placental insufficiency, foetalabnormalities and mortality, foetal malformations, preterm birth and low birth weight. However, theseobservations have not always been reported in other studies and the underlying mechanisms of theseeffects are still not known. In this study an unusually high number of embryos per recipient (calculatedto be about 230 embryos per recipient) were transferred compared with other reports in whichgenerally 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, osteopontinand fibroblast growth factor) involved in implantation and maintenance of pregnancy in pigs havebeen investigated (Kim et al., 2009b). The maternal uterine genes in pigs were aberrantly expressed tovarying degrees depending on the normality of the developing clone embryos. A uterus with aberrantgene 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 inthe 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 controlanimals (Jurie et al., 2009). The foetal origin of this delay has been further studied by investigatingmyogenesis of eight clone foetuses. The clone foetuses had a significantly lower number of myotubesat day 60 of pregnancy compared with controls and a retarded pattern of myosin isoforms by day 260of pregnancy indicating that disturbances in myogenesis occur early in the foetal life (Cassar-Malek etal., 2010b).


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To investigate DNA methylation, 5-methyldcytosine (5mC) levels in leukocyte DNA of 38 healthyfemale bovine clones, representing in total 9 genotypes (5 Simmental and 4 Holstein breeds) havebeen measured (de Montera et al., 2010). The absolute deviation in 5mC values of individual clonesfrom the means of their genotype showed a five fold increase in comparison with normal twins. Thisstudy 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 thatDNA 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 somaticcells and are similar to artificial insemination (AI) derived bulls. This suggests that any epigeneticaberrations that bull clones may harbour are unlikely to be passed on to their offspring through theirgametes.

Variations in haematological profiles were analysed between 47 clones and 23 controls from birthuntil 15 months of age in New Zealand (Green et al., 2009). Although most parameters were withinthe 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 havesimilar cognitive capacities of kin and non kin discrimination as control conventional cows (Coulon etal., 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 durationfor females, and 4 week duration for males) and compared with diets with normal meat or withoutmeat (Hwang et al., 2009). The daily food consumption in both of the meat groups (clone and normalmeat) were significantly lower compared with the control. This study used reproductive physiologicalmeasures and no obvious negative effects were seen in rats fed meat from clones compared withfeeding conventional meat.

Another study from the same group studied the effects on reproductive parameters in rabbits fed a dietwith meat from cattle clones during gestation (up to 27 days) (Lee et al., 2010a). No obviousdifferences in reproductive parameters were observed in pregnant rabbits fed meat from clonescompared to control. However, it should be noted that rabbits are herbivores and may not be a suitablemodel 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 andraised in the same experimental farm, confirmed that none of the F1 calves presented any of thepathologies observed in clones. They develop similarly to AI controls and differed from the clonesthemselves (Heyman et al., 2009). Oxidative and contractile characteristics of muscles have beeninvestigated by repeated biopsies from 10 heifers born from AI of clones collected at 8, 12 and 18months of age and compared with 8 AI controls and 9 clones (Cassar-Malek et al., 2010a). Theproportion of slow oxidative isoforms and fast glycolytic isoforms were not significantly differentfrom the AI controls.

No new information has been identified in relation to the impact of cloning on offspring from pigclones. Transgenerational studies in farm animals as well as long term behavioural studies have notbeen identified.


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6. Breeding and cloning efficiency

This section contains information outside the terms of reference and is provided based on discussionwith the Commission services. In this sense, this section is not an update since the 2009 statement or2008 opinion and includes information published over several years.

Measurement of cloning efficiency and comparison of cloning with other breeding technologies iscomplex 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 etal., 2009).

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

It should be recognised that with conventional breeding a significant proportion of oocytes fertilisedby sperm will not develop into a viable embryo and give rise to a live offspring. However, it should benoted that the information related to efficiencies of conventional breeding is not the focus of thisstatement and the information presented below is a reflection of only a few publications, mostlyfocusing 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. Breedingtechnologies 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 arecurrently widely used in the zootechnical practice without any underlying formal risk assessment, andsome, like artificial insemination have been used commercially since the 1930s (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 westernEuropean countries (Dominguez et al., 2009; Feitsma, 2009; Wahner and Geyer, 2007)); worldwidethe figures are 42 % and 50 % respectively (Wahner and Geyer, 2007; FAO, 2007). In some Europeancountries AI is used for the majority of cattle breeding (up to 90 %). The global conception ratesfollowing AI average 50-65 % in cattle and 70-80 % in pigs.

Fertilization rates by artificial insemination in heifers and moderate yielding dairy cows have beenestimated to be 90 % and average calving rates of about 55 %, indicating an overall embryonic andfoetal mortality rate of about 40 % (Sreenan et al., 2001). Another study of AI of cattle (in theHolstein Friesian breed) a fertilisation failure of 10 %, early embryonic mortality rate of 43 % and lateembryo 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 researchpurposes in farm animals, but to a limited extent (See review (Garcia-Rosello et al., 2009). Thistechnology has a low efficiency with birth rates ranging from 5.2 % to 50 % in various species.


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

6.2.

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

In Japan 575 cattle clones have been produced as of September 30, 2009 (Watanabe, 2010). Amongthe 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 survivalrate of 43 % of the born clones. A calving rate for some donor cell lines up to 60 % and even 90 % (asmall study, foetal fibroblast cells as donors, 10 embryos transferred to 10 recipients delivering 9 livecalves, 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 onemonth 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 RecherchAgronomique) indicate that of 90 calves born at term, 79 (87.7 %) were live at birth, 61 (67.8 %) werelive after 3 months and 67 (63.3 %) were live adults. This survival rate (63.3 %) is higher than the onereported from Japan (43 %).

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

6.3. Efficiency of pig cloning

For a successful recognition of pregnancy in sows, including natural breeding, at least four viableembryos need to be recognised and implanted to the uterine wall around day 14 post fertilization. Tocompensate for the low in vitro developmental capacity of pig clone embryos, a large number of cloneembryos are usually transferred. The most suitable number of embryos to be transferred to recipients isunknown. 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 withlitter 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 termresulting 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 555embryos to four recipients, three became pregnant and delivered 13 live-born piglets, corresponding toan efficiency of 1.9 % (Tomii et al., 2009). In a study using histone deacetylase inhibitor and earfibroblast as donor cells, 143 and 125 embryos respectively, were transferred into two recipients and10 piglets were born corresponding to 3.7 % efficiency (Zhao et al., 2010).


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

MethodsNo.

embryos/recipients (avg)

Pregnant toterm(%)

Number of piglets

born/litter

% Efficiency(born

piglets/embryostransferred)

SCNT(Walker et al.,2002)

59-128 (102) 80 7 6.9

(Petersen et al.,2008) (a)

80-162 (128) 75 5.2 4.0

(Estrada et al.,2007)

ND (c) ND (c) 6.2 ND (c)

(Schmidt et al.,2009)

40-60 36 4.4 ND (c)

IVF(Beebe et al.,

2009)24-35 (b) 67 5.3 11

(Kikuchi et al.,1999) 66-100 (89) 67 4.25 4.25

(Yoshioka et al.,2003) 20-25 (23)

(b) 100 5.3 24

(Kikuchi et al.,2002) 50

(b) 100 6.3 9

(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 embryoswould be equivalent to 25 Day 5-6 embryos. The embryos in the studies were transferred on aroundday 5-6. Consequently, the numbers of embryos transferred in the SCNT and IVF studies aresimilar.

(c): Not determined

6.4. Conclusion on cloning efficiency

Cloning efficiency in cattle (currently around 10 %) and pigs (currently around 6 %) is lower than bynatural 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 andembryo transfer in pigs, cloning has similar efficiency (~ 6 %).

C ONCLUSIONS

Based on the literature search and information provided in the framework of the present statement, it isconcluded that there is still limited information available on species other than cattle and pigs whichwould 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 bynatural 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 andembryo 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 suggeststhat 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


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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 2008scientific 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 asconsidered in the 2008 scientific opinion and the EFSA 2009 statement.


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DOCUMENTATION PROVIDED TO EFSA

During the call for data, published the EFSA website from 9 June to 9 July 2010 the followinginformation, 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.3pages. SCNT (in cattle). 7 pages. The submission also contained 29 publications.

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Jurie C, Picard B, Heyman Y, Cassar-Malek I, Chavatte-Palmer P, Richard C and Hocquette JF, 2009.Comparison of cloned and non-cloned Holstein heifers in muscle contractile and metaboliccharacteristics. Animal, 3, 244-250.

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APPENDIX 1. C ONCLUSIONS AND R ECOMMENDATIONS FROM THE EFSA 2008 SCIENTIFICO PINION

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 Healthand Welfare and Environmental Impact of Animals derived from Cloning by Somatic Cell NucleusTransfer (SCNT) and their Offspring and Products Obtained from those Animals. The EFSA Journal(2008) 767, 1-49

C ONCLUSIONS

Somatic cell nucleus transfer (SCNT) is a relatively new technology in animal reproduction withlimited data available and is increasingly being used in some countries to produce clones. These clonescan 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 smallsample sizes investigated and, in general, the absence of a uniform approach that would allow all theissues relevant to this opinion to be more satisfactorily addressed.

The health and welfare of a significant proportion of clones, mainly within the juvenile period forbovines and perinatal period for pigs, have been found to be adversely affected, often severely andwith a fatal outcome. Epigenetic dysregulation is considered to be the main source of adverse effectsthat 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 conventionalcounterparts based on parameters such as physiological characteristics, demeanour and clinical status.The production of clinically healthy clones provides evidence in those cases that the epigeneticreprogramming has taken place successfully.

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

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

R ECOMMENDATIONS

General recommendations

The health and welfare of clones should be monitored during their production life and naturallife span.

As food animals other than cattle and pig have also been produced via SCNT, risk assessmentsshould be performed on these species when relevant data become available.

This opinion should be updated in the light of developments in cloning and/or with new

relevant data.


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Additional recommendations

In relation to epigenetic and genetic aspects of SCNT it is recommended to determine or furtherinvestigate:

The role of the epigenetic dysregulation as a cause of adverse effects. Whether, and if so, to what extent epigenetic dysregulation occurring in clones is transmitted

to the progeny (F1). Whether, and if so, to what extent SCNT may induce silent DNA mutations. The possible consequences of mitochondrial heterogeneity in SCNT. The effects of telomere length in clones derived from different cell sources.

In relation to animal health it is recommended to:

Conduct further research on the possible effects of SCNT on the natural life span of cattle andswine clones.

Investigate further the causes of pathologies and mortality observed in clones during thegestational and postnatal periods and those observed at a lower frequency in adulthood.

Further investigate the immunocompetence and the susceptibility of clones and their offspringto diseases and transmissible agents when reared and kept under conventional husbandryconditions.

In relation to animal welfare it is recommended to:

Perform studies on animal welfare, including behavioural studies, in healthy clones undernormal husbandry conditions.

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:

Should evidence become available of reduced immunocompetence of clones (see animalhealth 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 increasedhuman exposure to transmissible agents.

The database on compositional and nutritional characteristics of edible animal productsderived from clones and their progeny should be extended.


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APPENDIX 2. SUMMARY OF EFSA 2009 STATEMENT

Below is the summary from the Statement of EFSA prepared by the Scientific Committee andAdvisory 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 EuropeanCommission to expand and further deepen the underlying details related to the recommendationsincluded in the animal cloning opinion of July 2008 (EFSA Journal (2008) 747, 1-49). The requestwas for EFSA to focus in particular on the health and welfare of animal clones and therecommendations related to investigation of the causes of pathologies and mortality observed in clonesduring the gestational and postnatal periods and those observed at a lower frequency in adulthood andthe health and welfare of clones during their productive life and natural life span. In addition theEuropean 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 thatSomatic 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 andthere are only a few publications and studies on postnatal or adult animals. If the success rate of theepigenetic reprogramming is improved it is likely that the pathologies and mortalities observed in aproportion 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 stillvalid.


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EUROPEAN COMMISSION

Brussels, 19.10.2010COM(2010) 585 final

REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT ANDTHE COUNCIL

on animal cloning for food production


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REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENTAND 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 RISKMANAGEMENT....................................................................................................... 1 0

9. OPTIONS................................................................................................................... 1 2

10. CONCLUSIONS........................................................................................................ 1 4


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1. INTRODUCTION

This report presents an assessment of cloning technology in relation to foodproduction. The objective is to examine the relevant aspects of cloning in light of thecurrent legislative framework.

Cloning 1 is a relatively new breeding technique which allows the asexualreproduction of animals that have shown good productivity, low incidence of diseaseand the capacity to cope with the production environment. The scope of the report islimited 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 otherbreeding technique, it is important to undertake risk assessments on critical aspects inorder 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, tradeimplications and the consumer's right to be informed about the production process.

An opinion of the European Food Safety Authority (EFSA) adopted on 15 July2008 2, cited difficulties in relation to the risk assessment of cloning due to the limitednumber of available studies. It also noted that the health and welfare of a significantproportion of clones had been found to be adversely affected, often severely and witha fatal outcome. The opinion found no indication of any differences in food safety forthe meat and milk of clones and their progeny compared with conventionally bredanimals. Finally, the opinion did not envisage environmental impacts, butacknowledged the limited availability of data.

On 26 June 2009, EFSA published a statement on further advice on the use of animalcloning 3. This statement confirmed the validity of the conclusions andrecommendations of the 2008 EFSA opinion, adding that the main source of theadverse effects that may affect clones and result in developmental abnormalities was"epigenetic dysregulation" 4. Failure of the placental development following cloningis believed to be one of the reasons why the technique has a low success rate.Adverse affects, however, vary between species. For example, large offspringsyndrome (LOS) affects cattle but not pigs. This condition can result in difficult birthand health problems for the surrogate dams and cases of stillbirth. Neither of thesephenomena appears to affect the offspring of clones, born through conventionalbreeding techniques.

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

1 For the purposes of this report (and in common with EFSA and EGE Opinions) cloning refers toreplication by somatic cell nuclear transfer (SCNT) to create genetic replicas (clones) from adultanimals that share the same

animal cloning for food production (report by u.k. food standards agency)

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