ANIMAL CLONING AND GENETIC MODIFICATION: A PROSPECTIVE STUDY
Report 3 to
Institute for Prospective Technological Studies (IPTS)
Seville
October 2005
GM animals
Socio-economic issues
Anette Braun[5]
Ann Bruce[1]
Renate Gertz[2]
Cecilia Oram[3]
Jonathan Suk1
Joyce Tait1
Chris Warkup3
Bruce Whitelaw[4]
Acknowledgements
We would like to thank the participants of the one day hearing held at Innogen as part of this project and also Eileen Mothersole for contributing her secretarial expertise.
List of Contents
Executive Summary
SECTION 1 INTRODUCTION
1.1 Introduction
SECTION 2 OVERVIEW OF THE LEGAL FRAMEWORK
2.1 Overview of the legal frameworks
2.2 EU legislation
2.2.1 GMOs for deliberate release in the environment
2.2.2 Traceability
2.2.3 GM foods
2.2.4 Food Safety Legislation
2.2.5 Pharmaceutical products
2.2.6 Xenotransplantation
2.3 The regulation of GM animals worldwide
2.3.1 USA
2.3.2 Canada
2.3.3 Australia
2.3.4 New Zealand
2.3.5 Singapore
2.3.6 China
2.3.7 Japan
2.3.8 Korea
2.3.9 Conclusions
2.4 International regulation
2.4.1 The Cartagena Protocol on Biosafety
2.5 Nutraceuticals and Functional Foods
2.5.1 EU
2.5.2 USA
2.5.3 Japan
2.5.4 Conclusions
2.6 Patenting GM animals
2.6.1 The regulation of patenting on an international level
2.6.2 Patenting legislation in the EU
2.6.3 Patenting legislation worldwide
SECTION 3 RISKS AND RISK ASSESSMENT
3.1 Risks from GM animals
3.1.1 Food safety issues
3.1.2 Pharmaceutical safety issues
3.1.3 Xenotransplantation safety issues
3.1.4 Environmental risks from releases to the environment
3.1.5 Disease risk to current animals
3.2 Risk assessment
3.2.1 Risk and regulation of transgenic animals in the EU
3.2.2 Risk and regulation of transgenic animals in the USA
3.2.3 Risk and regulation of transgenic animals in New Zealand
3.2.4 Japan
3.2.5 Conclusions
3.2.6 International risk assessment approaches
SECTION 4 INTERNATIONAL TRADE AND LABELLING ISSUES
4.1 International regulation of trade in GM animals and related products
4.1.1 WTO – Sanitary and Phytosanitary Measures (SPS)
4.1.2 WTO – Technical Barriers to Trade (TBT)
4.1.3 GATT 1994 and the product/process distinction
4.1.4 Cartagena Biosafety Protocol and WTO – potential areas of dispute
4.2 Additional potential trade issues
4.2.1 Implications of international agreements for Developing Countries
4.2.2 Unanticipated and illegal trade
4.3 Labelling
4.3.1 The Codex Alimentarius
4.3.2 The WTO
4.3.3 Labelling in individual jurisdictions
4.4 Traceability
SECTION 5 ANIMAL WELFARE
5.1 Welfare of GM animals
5.1.1 Introduction
5.1.2 Physiological issues
5.1.3 Health issues
5.1.4 Behavioural issues
5.1.5 Conclusions on comparison of GM and non-GM animals
5.2 Regulation on animal welfare
SECTION 6 PUBLIC ATTITUDES
6.1 Introduction
6.2 Attitudes to GM animals
6.2.1 Europe
6.2.2 USA
6.2.3 Japan
6.2.4 Developing countries
6.3 Ethical discussions around GM animals
6.4 Dilemma of human – animal relationships
SECTION 7 POLICY CONTEXT
7.1 Ethical Policy
7.2 EC Biotechnology Strategy
7.3 Industry context: pharmaceutical and agricultural
7.4 Developing countries’ context
SECTION 8 META-ANALYSIS OF GOVERNMENTAL TECHNOLOGY FORESIGHTS AND ASSESSMENTS
8.1 Introduction
8.2 Aim and objective
8.3 Findings: (inter)national technology assessments
8.4 Findings: (inter)national technology foresight
8.5 Outlook
SECTION 9 CASE STUDIES
9.1 GM animals as bioreactors
9.1.1 Aim
9.1.2 Markets
9.1.3 Technical aspects
9.1.4 Drivers
9.1.5 Regulation
9.1.6 Special issues
9.1.7 Public attitudes
9.1.8 EU Competitiveness
9.1.9 Alternative approaches
9.2 Faster growth rate from GM animals
9.2.1 Aim
9.2.2 Markets
9.2.3 Technical aspects
9.2.4 Drivers
9.2.5 Regulation
9.2.6 Special Issues
9.2.7 Public attitudes
9.2.8 EU Competitiveness
9.2.9 Alternative approaches
9.3 GM animals for food
9.3.1 Aim
9.3.2 Markets
9.3.3 Technical aspects
9.3.4 Drivers
9.3.5 Regulation
9.3.6 Special issues
9.3.7 Public attitudes
9.3.8 EU Competitiveness
9.3.9 Alternative approaches
9.4 GM Pets
9.4.1 Aim
9.4.2 Markets
9.4.3 Technical aspects
9.4.4 Drivers
9.4.5 Regulation
9.4.6 Special issues
9.4.7 Public attitudes
9.4.8 EU Competitiveness
9.4.9 Alternative approaches
9.5 Xenotransplantation
9.5.1 Aim
9.5.2 Markets
9.5.3 Technical aspects
9.5.4 Drivers
9.5.5 Regulation
9.5.6 Special issues
9.5.7 Public attitudes
9.5.8 EU Competitiveness
9.5.9 Alternative approaches
SECTION 10 REFLECTIONS
SECTION 11 REFERENCES
SECTION 12 APPENDICES
Appendix 1 - Acronyms
Appendix 2 - Selected Web sites
Appendix 3 - ANNEX II of EU Directive 2001/18/EC: Environmental Risk Assessment
Appendix 4 - Annex III of the Cartagena Biosafety Protocol: Risk Assessment (Available from:
List of Tables
Table 1 Summary Table of US Regulatory System
Table 2 Specific issues related to foods derived from animal biotechnology
List of Figures
Figure 1 Roadmap demonstrating the drivers for GM animals as bioreactors
Figure 2 Roadmap demonstrating drivers for products from faster growing GM fish becoming available in the EU
Figure 3 Roadmap demonstrating the drivers for GM animal food products in the EU
Figure 4 Roadmap demonstrating the drivers encouraging availability of pet GM fish in the EU
Figure 5 Roadmap demonstrating the drivers to the availability of xenotransplants in the EU
Executive Summary
There are a large number of possible applications of GM animals, including:
- Agricultural use for food production (including fish)
- Production of pharmaceuticals in the milk, eggs and blood of animals
- Production of organs for transplant into humans (xenotransplantation); and
- Production of specific types of pets.
However, we identified relatively little activity within each area of application. Genetically modified animals were first created at the research level in 1985;but have not progressed to commercialisation in the way that has happened with GM crops. We have not identified any approved use of GM livestock in the food sector anywhere in the world. GM ornamental fish are on sale in the USA and pharmaceuticals produced in GM animals may be commercially available in the EU in the next few years.
Food Production
The lead product is probably genetically modified fish, including faster growing GM salmon developed in North America which are waiting regulatory approval for use in the food chain. Other applications are being considered at the experimental stage, but is seems unlikely that any will be in general use before 2010.
We have not identified any companies in the EU developing GM animals for food. GM foods are extensively regulated throughout the EU and elsewhere in the world but most of these regulatory systems have been developed for crops rather than livestock. It is not clear to what extent these regulatory requirements are compatible. Unlike crops, environmental risk is not perceived to be a major concern with food-producing animals, with the exception of fish. Risk issues are therefore more concentrated on risks to human health. Animal welfare is however an additionalconcern with GM animals.
The EU has clear regulatory requirements with respect to releases to the environment, labelling and traceability of GM and GM-derived foodstuffs, as well as safety assessment of GM foods. At the international level, the Cartagena Protocol on Biosafety to the Convention on Biodiversity applies to GM animals but compatibility of different international regulatory regimes is less clear, as is evident from the current dispute in the World Trade Organisation between USA and EU concerning GM crops. The outcome of this dispute may be influential in subsequent developments with regard to GM animals.
Although there is a legal requirement to label GM products in the EU (and many other jurisdictions), as there is currently no reliable method for detecting all GM animals,it may be difficult to prevent accidental mixing or deliberate illegal trade. The situation is likely to be even more difficult with respect to products derived from GM animals, such as milk.
The USA does, however, have different regulatory regimes for GM plants and GM animals. Following their practice of regulating according to the product rather than process, there are a number of different ways in which GM animals may be regulated depending on the intended use of the product. The Food and Drug Administration’s approach to GM plants and crops is based upon ‘substantial equivalence.’ GM crops are not normally subject to pre-market review since they are generally considered to be ‘substantially equivalent’ to conventional counterparts. With respect to animals, it seems likely that the most common approach will be to consider genetic constructs and their expression products as ‘animal drugs’. This will require a case-by-case pre-market assessment of products, with the onus on the producers to demonstrate safety. It is noteworthy, however, that an application of GM animals to improve the quality of the food product would be more likely to be evaluated under the ‘Generally Recognized as Safe’ procedures.
Production of pharmaceuticals
As stated in Report 1, one of the most likely applications to be available commercially within the next 5 years is pharmaceuticals produced by GM animals (so called ‘bioreactors’ or ‘pharming’). We identified a small number of companies in the EU active in this area. The major barrier to development appears to be meeting regulatory requirements. Whilst the regulatory system for pharmaceuticals generally is well co-ordinated in Europe under the auspices of the European Medicines Agency (EMEA), it is not clear that there is a specific regulatory route for biologics derived from ‘bioreactors’. Furthermore, EMEA’s focus is on safety and efficacy of the product and regulation of other factors such as releases to the environment and accidental (or deliberate) releases into the food chain are regulated by other bodies, as for GM crops.
Production of organs for transplant
The production of GM pigs to supply organs for human transplants has been the subject of considerable research effort. We have not identified any examples of xenotransplantation products from GM livestock that are currently on the market or available for treatments. Various degrees of optimism are expressed about the prospects for xenotransplantation but most proponents suggest that it will be 10 years or more before GM pig organ transplants become available. Several European countries have considered regulation of xenotransplantation and deemed it allowable only if certain ethical and safety considerations are met. There is currently no unifiedregulatory system for xenotransplantation in the EU.
Pets
GM ornamental fish have been available commercially in the USA since late 2003, and these are essentially unregulated. Research is reportedly also being conducted to produce GM cats with reduced allergenicity for humans. Import of such animals into the EU would be covered under existing GM regulation.
Welfare and ethical issues
One of the most contentious issues with regard to use of GM animals is the welfare and ethical issues which these raise. GM animal welfare may need a case-by-case assessment, both predictive and through monitoring of test GM populations for several generations.Relatively little information appears to be available on attitudes to particular applications for specific purposes, rather than GM animals in general. However, extensive ethical reflection has been carried out, particularly with respect to xenotransplants, although this does not necessarily mean that there is universal agreement on the ethical considerations.
Genetically modified and cloned animals
Somatic Cell Nuclear Transfer (cloning) is being used in conjunction with genetic modification, as a technique which enables genetic modification. Since there is little regulation specific to cloning, the main regulatory issues will be around genetic modification. Within Europe, there are a few exceptions. Denmark has recently enacted regulation which restricts the use of GM and cloning only to research purposes for health and environmental benefits. In Norway, legislation prohibits cloning and this is also likely to apply to animals which are GM and cloned.
Technology assessment and foresight
Animal biotechnology presents many challenges and opportunities for government regulators and the public in all nations. The technology is often controversial even within one country. The complexities multiply when considering the regulation of animal biotechnology in several nations. This is reflected in the way in which different counties are assessing, validating and judging this technology in order to ensure that regulationis efficient and safety maintained.
SECTION 1 INTRODUCTION
1.1 Introduction
The purpose of this report is to identify potential socio-economic impacts (benefits and risks) and new policy implications arising from the development of Genetically Modified (GM) animals to the EU and of the commercialisation of products from genetically modified animals. Furthermore the aim is to compare regulatory frameworks and visions world-wide.
GM animals are being developed for a number of different applications such as production of pharmaceuticals, organs for transplantation and meat and milk for human consumption. A full description of applications of GM animals is given in Report 1. GM animals may also be used as experimental tools to understand fundamental biology and model human diseases, but these applications were excluded from our remit. In some cases somatic cell nuclear transfer (SCNT) cloning is used in conjunction with genetic modification as the processes of SCNT enables GM to be carried out, as described in more detail in Report 1. Ethical questions and public concerns are only briefly considered in this report as they are the subject of a larger EC Specific Support Action on ‘Farm Animal Cloning and the Public’. Within this report the term ‘cloning’ should be understood to mean SCNT cloning unless otherwise stated and the term ‘animal’ should be understood to refer to non-human animals only. Genetic markers are also being applied to livestock by breeders (Marker Assisted Selection) and are the subject of considerable research effort to better understand genetics and gene function in farm livestock. These applications (broadly defined as farm animal genomics) were excluded from our remit. Issues raised by the development of cloned animals are covered separately in Report 2.
This report is in 12 sections.
- Section 1 is an introduction.
- Section 2 gives an overview of the regulatory frameworks.
- Section 3 considers the risks from GM animals and the risk assessment methods adopted by regulatory bodies.
- Section 4 considers issues around international trade in GM animals and the products from GM animals, including labelling issues
- Section 5 considers the issues around physiological animal welfare
- Section 6 considers public attitudes
- Section 7 considers the policy contexts and visions around GM animals
- Section 8 gives a meta-analysis of governmental technology foresights and assessments
- Section 9 considers Case Studies of applications of GM animals.
- Section 10 Reflections
- Section 11 References
- Section 12 Appendices
This study was conducted March-September 2005. The scientific aspects were investigated by staff at Roslin Institute, the commercialisation activities by staff at Genesis Faraday Partnership, legal aspects by staff at the Centre for Studies in Intellectual Property and Technology Law, technology foresights and assessments by VDI and the risk assessment, trade and socio-economic aspects by staff at the Innogen Centre. The methodology consisted primarily of literature and web surveys. A one-day ‘hearing’ was held at Innogen on Sept. 5th to bring a number of different types of expertise to bear on the subject, including experts in innovation processes. Additionally, useful interchange of information took place with the Specific Support Action “Farm animal cloning and the public” and in a 2-day workshop held in Seville in June 2005, co-organised by the IPTS and the above mentioned SSA.
SECTION 2 OVERVIEW OF THE LEGAL FRAMEWORK
2.1 Overview of the legal frameworks
There are a large number of possible areas where GM animals may be developed, including:
- Agricultural use for food production
- Production of organs for transplant into humans (xenotransplantation)
- Production of pharmaceuticals in the milk, eggs and blood of animals; and
- Production of specific types of companion animals (pets)
As stated in Report 1, the most likely applications to be available commercially within the next 5 years are pharmaceuticals produced by animals (so called ‘bioreactors’) where some products are in late clinical trials and companion animals (such as ornamental fish), which are already available commercially in the USA. Applications for xenotransplantation and food production appear to be further away from commercial reality.
Because of this extensive range of applications, the range of different regulations that must be considered is also extensive.
If cloned animals are also genetically modified, then, as there is a lack of legislation specific to animal cloning in Europe, the legislation regulating the genetic modification of animals will apply. Exceptions are Norway and Denmark as these countries have specific legislation regarding animal cloning, the details of which are given in Report 2.
2.2 EU legislation
In contrast to animal cloning, genetic modification of animals has been extensively regulated in the EU, largely due to the commercialisation of GM crops. Community legislation on GMOs designed to protect its citizens’ health and the environment while simultaneously creating a unified market for biotechnology has been in place since the early 1990s and throughout the decade, the regulatory framework has been further extended and refined.
2.2.1 GMOs for deliberate release in the environment
While the contained use of genetically modified micro-organisms, e.g. laboratory research (in a confined environment), is regulated by Directive 90/219/EC on the contained use of genetically modified micro-organisms, Directive 2001/18/EC provides the legislation governing the release of GMOs into the environment e.g. for cultivation, import or processing into industrial products, by putting in place a step-by-step approval process, based on a case-by-case assessment of the risks to human health and the environment before any GMO or product consisting of or containing GMOs can be released into the environment or placed on the market.
In order to market a GMO, the company must first submit an application to the competent national authority of the MemberState where the product is to be first placed on the market. A full environmental risk assessment must accompany the application. If the national authority gives a favourable opinion, the MemberState notifies the Commission, which then in turn informs the other Member States. If neither Commission nor Member States object, the competent authority that carried out the evaluation then consents to the product being placed on the market throughout the European Union subject to any conditions required in that consent.
In the case of objections, a decision will be taken at Community level. The Commission first obtains the opinion of its Scientific Committees and, if this opinion is favourable, proposes a draft Decision to the Regulatory Committee composed of representatives of Member States for opinion. If this opinion is also favourable, the Commission adopts the Decision. If any of the opinions is unfavourable, the draft Decision is submitted to the Council of Ministers for adoption by qualified majority or rejection. If the Council does not act within 3 months, the Commission can adopt the decision.
2.2.2 Traceability
Products consisting of or containing GMOs and food products obtained from GMOs which have been authorised on the basis of the procedure under Directive 2001/18/EC (Part C) or Regulation (EC) No 1829/2003 are also subject to traceability requirements according to Regulation (EC) No 1830/2003.
Traceability in this connection is the ability to track GMOs and food products obtained from GMOs at all stages, throughout the production and distribution chain. The traceability rules requires anyone who places a product on the market or receives a product placed on the market in the Community to be able to identify their supplier and the companies to which the products have been supplied. If products consist of or contain mixtures of GMOs to be used only and directly as food or feed or for processing, replacing this information by a declaration of use by the operator is permissible, if the declaration is accompanied by a list of the unique identifiers for all those GMOs that have been used to constitute the mixture.