Proposal for a Council Decision adopting a specific research, technological development and demonstration programme in the field of biotechnology (1994-1998) (94/C 228/08) (Text with EEA relevance) COM(94) 68 final - 94/0086(CNS)

(Submitted by the Commission on 30 March 1994)

THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty establishing the European Community, and in particular Article 130 I (4) thereof,

Having regard to the proposal from the Commission,

Having regard to the opinion of the European Parliament,

Having regard to the opinion of the Economic and Social Committee,

Whereas, by its Decision . . ./. . ./EC, the Council and the European Parliament adopted a Fourth Framework Programme for Community activities of research, technological development and demonstration (hereinafter RTD), for the period 1994 to 1998, specifying, in particular, the activities to be pursued in the field of biotechnology; and that the present decision is taken in the light of the reasons given in the preamble of the aforesaid Decision;

Whereas Article 130 I (3) foresees that the framework programme is to be implemented through specific programmes developed within each activity; and that each specific programme shall define the detailed rules for implementing it, fix its duration and foresee the means deemed necessary;

Whereas this programme is implemented mainly through shared cost and concerted actions and accompanying and support measures;

Whereas in accordance with Article 130 I (3), it is appropriate to make an estimate of the means deemed necessary for the realization of this specific programme; and that the funds effectively available shall be determined by the budgetary authorities according to the relative priorities given within the First Action of the Fourth Framework Programme;

Whereas the Decision . . ./. . ./EC (Fourth Framework Programme) foresees that the overall maximum amount available for the Fourth Framework Programme will be reviewed no later than 30 June 1996 in view of being increased, and that as a result of this review, the amount deemed necessary to implement the present programme could be supplemented;

Whereas research in biotechnology may lead to improvements in agricultural and industrial efficiency and viability, greater protection of the environment and health and a better quality of consumer products;

Whereas this programme is able to contribute usefully to the relaunch of the growth, to strengthening and competitivity and the development of employment in the Community, as indicated in the White Paper on 'Growth, Competitivity and Employment' (1);

Whereas the contents of the Fourth Framework Programme for Community RTD activities have been defined in conformity with the principle of subsidiarity; and that this programme sets out detailed contents of activities in conformity with this principle in the field of biotechnology;

Whereas the Decision . . ./. . ./EC (Fourth Framework Programme) foresees that a Community activity is required if, among other reasons, the research contributes to the economic and social cohesion of the Community and encourages the overall harmonious development of the quality of its science and technology and that the present programme is supposed to contribute to the realization of these objectives;

Whereas this programme and its implementation contributes to improving the synergies between the RTD activities in the field of biotechnology, by research centres, universities and industry, in particular small and medium-sized enterprises (SME), established in the Member States, and between these and the corresponding Community RTD activities;

Whereas the rules for the participation of firms, research centres (including the IRC) and universities, as well as the rules governing the dissemination of research results, are laid down in the measures foreseen by Article 130 J;Whereas for the implementation of this programme, besides associating with the European Economic Area (EEA) countries other international cooperation activities might be necessary, in accordance with Article 130 M, with other third countries and international organizations;

Whereas the implementation of this programme also implies activities for the dissemination and exploitation of RTD results, in particular towards SMEs (small and medium-sized enterprises), and notably those located in Member States or regions which have the lowest participation in the programme, as well as activities to promote mobility and training of researchers carried out within this programme and in so far as necessary for its adequate implementation;

Whereas the implementation of this programme requires the provision of measures intended to encourage participation of SMEs, in particular technology stimulation measures;

Whereas basic research in biotechnology must be encouraged throughout the Community because it provides a source of innovation offering a large range of scientific opportunities to meet the real needs of society;

Whereas an assessment should be made of the socio-economic impact and of any technological risks, of the activities undertaken in this programme;

Whereas, on the one hand, this programme's state of implementation should be reviewed in a permanent and systematic way, in order to adapt it, where necessary, to the scientific and technological developments in this field; and on the other hand, an independent evaluation should be conducted, in due time, on the results achieved by the programme, in order to provide every appropriate information as necessary to determine the goals of the Fifth RTD Framework Programme; and that, a final evaluation will be necessary at the end of the programme to assess the results obtained in terms of the objectives defined in this Decision;

Whereas, on 23 April 1990, the Council adopted Directive 90/219/EEC on the contained use of genetically modified micro-organisms (2) and Directive 90/220/EEC on the deliberate release into the environment of genetically modified organisms (3);

Whereas the JRC may participate in the indirect actions covered by this programme;

Whereas the Scientific and Technical Research Committee (Crest) has been consulted.HAS ADOPTED THIS DECISION:

Article 1

A specific programme of research, technological development and demonstration in the field of biotechnology as defined in Annex I is hereby adopted for a period beginning on (date of adoption) and ending on 31 December 1998.

Article 2

1. The funds estimated as necessary for the execution of the programme amount to 552 MECU, including 7,5 % for staff and administrative expenditure.

2. An indicative allocation of funds is set out in Annex II.

3. The funds estimated as necessary as indicated above may be increased. As a result of and in conformity with the decision mentioned in Article 1 of paragraph 3 of the Decision . . ./. . ./EC (Fourth Framework Programme).

4. The budgetary authority shall lay down the available appropriations for each financial year in agreement with the scientific and technological priorities fixed by the Fourth Framework Programme.

Article 3

Detailed rules for the implementation of the programme, besides those provided for in Article 5, are set out in Annex III.

Article 4

1. The Commission shall review in a permanent and systematic way, with appropriate assistance from independent external experts, this programme's state of implementation, considering the objectives set out in Annex I, and in particular whether the objectives, the priorities and the funds are still adequate to the changing situation. Where necessary, this review shall be accompanied by proposals to adapt or complete this programme, in accordance with the review's conclusions.

2. In order to contribute to the global assessment of the Communities activities provided for in Article 4 (2) of the Decision adopting the Fourth Framework Programme, an evaluation of the management and the results achieved by the activities undertaken in the fields covered by this programme, during the five years preceding the evaluation, shall be conducted in due time for the Commission by independent experts.

3. At the end of this programme, the Commission shall conduct a final evaluation by independent experts of the results obtained concerning the objectives defined in Annex III of the Fourth Framework Programme and in Annex I of this Decision. It shall submit the final evaluation report to the Council, the European Parliament and the Economie and Social Committee.

Article 5

1. A work programme shall be drawn up by the Commission in accordance with the aims set out in Annex I and updated where necessary. It shall set out the detailed scientific and technical objectives and define the implementation stages of the programme, as well as the financial arrangements for each type of implementation to be undertaken.

The work programme can also allow participation in some activities originating from the Eureka framework.

2. The Commission shall make calls for proposals of RTD projects, on the basis of the work programme.

Article 6

1. The Commission shall be responsible for the implementation of the programme.

2. For measures foreseen in Article 7 (1), the Commission shall be assisted by a committee composed of representatives of the Member States and chaired by the representative of the Commission.

The representative of the Commission shall submit to the committee a draft of the measures to be taken. The committee shall deliver its opinion within a time limit which the chairman may lay down according to the urgency of the matter. The opinion shall be delivered by the majority provided for in Article 148 (2) of the Treaty as regards adoption of decisions which the Council is required to adopt on a proposal from the Commission. The votes of the representatives of the Member States within the committee shall be weighted in the manner set out in that Article. The chairman shall not vote.

The Commission shall adopt the measures envisaged when they are in accordance with the opinion of the committee.

When the measures envisaged are not in accordance with the committee's opinion, or if no opinion is delivered, the Commission shall without delay submit to the Council a proposal relating to the measures to be taken. The Council shall act by qualified majority.

If, on the expiry of a period of one month from referral of the matter to the Council, the latter has not acted, the proposed measures shall be adopted by the Commission.

Article 7

1. The procedure laid down in Article 6 (2) shall apply to:

- the preparation and updating of the work programme referred to in Article 5 (1),

- the assessment of the RTD projects proposed for a Community contribution and of the estimated amount of this contribution on a project basis, where this amount exceeds ECU 0,5 million,

- the measures to be undertaken to evaluate the programme,

- any adaptation of the indicative breakdown of the amount set out in Annex II, not having been decided through the budgetary procedure.

2. The Commission shall inform the committee, for each of its meetings, of the current state of implementation of the programme as a whole.

Article 8

The Commission is authorized to negotiate, in accordance with Article 228 (1), international agreements with European third countries with a view to involving them in all or part of the programme.

Article 9

This Decision is addressed to the Member States.

(1) COM(93) 700 final of 5. 12. 1993.

(2) OJ No L 117, 8. 5. 1990, p. 1.

(3) OJ No L 117, 8. 5. 1990, p. 15.

ANNEX I

SCIENTIFIC AND TECHNICAL OBJECTIVES AND CONTENT

This specific programme fully reflects the approach embodied in the Fourth Framework Programme, applies its selection criteria and specifies its scientific and technological objectives.

Paragraph 4.A of Annex III, first activity of the abovementioned framework programme, is an integral part of this programme.

THE BACKGROUND

The Commission has presented in its White Paper on growth, competitivity and employment, an analysis of the potential of biotechnology to present certain promises based on the omnipresence of the bioprocesses and the competitiveness of sectors of application, but identifying weaknesses on which Community efforts should have priority. The economic sectors whose competitiveness significantly depends on biotechnology (pharmaceuticals, chemicals, agriculture, food) account for the employment of 16,4 million people in Europe and exports worth 132,8 billion ECU. Europe has roughly 600 companies involved in some aspect of modern biotechnology, including a number of world-class chemical and pharmaceutical companies. The sustained growth of these sectors depends on a strong and innovative science base; a highly trained and skilled workforce; the efficiency of technology transfer from the science base to industry; the rapidity with which novel and innovative techniques are incorporated into established practices; the adoption of a multidisciplinary approach to biotechnology-based processes; the validation of scientific principles to underpin a unified market of biotechnology-derived products; and the harmonious application of bioprocesses as beneficial alternatives to promote the environment, human health and welfare. Progress along these lines will ensure that the estimated sales of non-food biotechnology products of 26-41 billion ECU by the year 2000 can be realized with a prominent European participation and a high degree of social acceptance. This situation is historically unique, as it brings biotechnology into the present reality of scientists, policy makers and industry, whereas earlier research programmes had been based on future promise.

Particularly relevant to bringing the life sciences to play an increasing role in the society will be the arrival on the market, under the period covered by the Fourth Framework Programme, of the first generation of transgenic plants endowed with useful new properties, of safer and more efficient vaccines deriving from rDNA work or of natural antimicrobial substances preventing microbial spoilage of food products.

While two other programmes, on biomedical and health research and on agriculture and fisheries research, shall promote the applications of biotechnology within their respective sectoral activities linked to the provision of goods and services, the Biotechnology programme itself shall create further opportunities by deliberately penetrating the heart of living systems. The flow information between those three will be the key to success.

It will be the responsibility of Community to promote under this programme further research work where the society would expect the highest returns. This points to privileged areas for the exploitation of new knowledge, all of which do experience in common an acute need for cross-linking connected topics and/or integrating large groups of experts on an international scale. The same integrative effort will be required for putting safely living cells to work, for raising the profile of the European contribution to the international genome projects, for achieving the new deal of modern agriculture and environment via the genetic design of crops or animal health control, or overcoming academic distinctions between neurobiology, endocrinology and immunology until the principles of cell and molecular interactions are unravelled. International collaboration with the Human Frontier Science Programme will be strengthened, as will be the links with Eureka projects and national programmes within the Community. Throughout the programme, careful attention will be given to the delicate step which brings research results in the context of socio-economic needs. In specific instances, demonstration projects may be established, and competent monitoring of the ethical and social parameters of public acceptance will be pursued.

This programme is implemented, as appropriate, in coordination with the specific programmes Information technologies, Measurement and Testing, Environment, and Targeted Socio-economic research.

Measures intended to encourage participation of SMEs, in particular technology stimulation measures and links between science parks and biotechnology SMEs, as recommended by the White Paper on Growth, Competitiveness, Employment, will be implemented.

THE PROPOSED RTD ACTIVITIES

The centre of any biological process in nature or in systems domesticated by man really is the living cell, which functions as a minute factory.

Each cell consumes its raw materials, converts energy, produces high value molecules as well as wastes, and has learned through evolution how to carry out those constructive processes in equilibrium with its environment. An infinite number of cells in living organisms bred for agricultural purposes, or in fermenters conducted for the industrial supply of valuable molecules, all behave as populations of clean productive units which can be exploited in a sustainable manner. In an attempt to focus biotechnology where it genuinely differs from alternative technologies, all efforts must start with a thorough understanding of how the cell manages to be so successfully industrious.

OBJECTIVES REQUIRING CONCENTRATED MEANS

Area 1: Cell factories

Industrial and environmental exploitations of living cells would hardly be achievable without a global approach integrating contributions from biological disciplines, computer science and process engineering which they have to depend on. New interfaces between biotechnology and advanced technologies offer opportunities for the integration of biology also with other sciences and technological fields. A multidisciplinary vision of cell factories must be promoted, with the intertwined participation of academic and industrial laboratories.

The primary objective is to reach an understanding of how living cells, particularly microorganisms and animal cells, manage to be productive and how industry can learn from cellular processes in order to design and operate safe, specific and sustainable bioprocesses.

Optimal use should be made of relevant biological knowledge generated from studies on: cell biology and signalling, macromolecular interactions, protein folding and secretion, post-translational modifications, genetic stability, microbial physiology and biodiversity, the control of metabolic fluxes, extremophily, antimicrobials, etc. Support will be given where the combination of this biology with engineering approaches is most likely to realize the biotechnological potentials of cell factories, particularly in fields such as: the fundamental aspects of fermentation, biotransformation, biocatalysis, biosensors, process control with neural networks, of technologies cell culture and co-culture, downstream processing, etc.

The research tasks will be concentrated on relevant generic topics of interest to industry and other end-users of biotechnology. A typical project will require the integration of biological and bioengineering disciplines and will be aimed at solving gaps in basic knowledge as well as technological barriers which prevent the full exploitation of the cell's capability as a factory for the conversion or production of useful biomolecules.

The biosafety of vector systems, cell lines and microbial cultures will be an important consideration of any project selected for this action.

In order to optimize Community resources and exploitation of research results, bioprocess engineering activities will be synergistically and closely coordinated with the contributions invited under the programme on Industrial Technologies, or under the Agriculture and Fisheries Research Programme which covers interrelated work applying processing, end-use and scaling-up technologies adapted to industrial conditions. The emphasis of cell factories is in the development and optimization of generic technologies potentially applicable to a large number of sectors.

Area 2: Genome analysis

The participation of European networks in the worldwide genome programmes will be facilitated via the further analysis and sequencing of model genomes, such as Bacillus subtilis, Saccharomyces cerevisiae and Arabidopsis thaliana. The mapping and sequencing projects will combine efforts to unravel new genes with attempts to study genetic function; they will make a new effort to encourage the development of novel software and other bioinformatic tools and, where appropriate, to integrate the development and extension of the methodological and instrumentation basis. Also relevant transcriptional and replicative mechanisms will be investigated, as well as higher levels of organization of the genomes, such as now made possible by the new knowledge of complete chromosome composition and structure becoming gradually available.

Methodologies will be set-up and applied to render possible the association of detailed biological functions with newly unravelled genes from any appropriate model genome. A systematic approach to function search will be allowed through networks of specialized laboratories which on the basis of mutated, deleted or over-expressing strains carrying uncharacterized genes, will rely on standardized tests pointing the way towards the associated functions. Conversely, targeted approaches to biotechnologically important functions will be encouraged through the submission of proposals by consortia willing to screen, in yeast for example, the collection of disrupted mutants against pre-defined phenotypic alterations with a view to identifying sets of genes coding for industrially relevant pathways. Special attention will be given to additional innovative approaches (i.e.: based on mRNAs, gene structure or promoter similarities, etc.) exploitable for harvesting the maximum biological benefits from existing genome projects. By bridging the gap between sequencing activities and the functional characterization of sequences, another entry into the cell factory concept will be provided from the specific angle of the genetic control of metabolic pathways.

Comparative methods will be exploited across different genomes including the human genome. These approaches will include the development of new mapping procedures based on the use of homologous DNA probes from model genomes, heterologous expression through cDNAs in bacteria or fungi and development of new informatic software to improve detection of functional or structural homologies. The development and sharing of advanced technologies and a decentralized pool of exchangeable clones, probes and data will be organized.

With a view on possible medical applications, work on the human genome will be concentrated in the Biomedical and Health research programme. However, comparative approaches and related technology developments will include human DNA and, with respect to human cells, the same limitations will be applied, i.e. alteration of germ cells or any stage of embryo development with the aim of modifying human genetic characteristics in a hereditary manner is excluded from the programme objectives. The coordination with accompanying measures on the ethical, social and legal aspects, executed elsewhere in the programme, will be emphasized.

Area 3: Plant and animal biotechnology

Plant molecular and cellular biology

Plant molecular and cellular biology, including protein engineering, physiology and pathology, at the crossroads of agricultural, industrial and environmental issues, will be developed by stressing the need for an integrated research. Particular attention will be given to the molecular understanding and eventual modification of relevant plant processes as an approach leading to new tailor-made market-relevant agricultural or forestry products, and to production methods compatible with the environment, health and consumers' demand, which areas are included within the Agriculture and Fisheries Research Programme. Identifying, characterizing and exploiting useful biological traits of agricultural and industrial relevance, in terms of quality improvement and greater environmental acceptability, and their corresponding genes would be the main target for such activity.

These include: pest and disease resistance; stress tolerance; quality and quantity of starch, oils, valuable protein, pharmaceuticals in leaves, seeds, roots, etc., at the cell level; developmental pathways, reproduction and regeneration; improved enzymes and macromolecules for processing.

Underpinning science will have to be considered, such as that allowing control of heterologous expression and of stability of expression, cell structural analyses (to understand and regulate the traffic of molecules), or identification of nutritional and health properties of food and feed components (to fine tune molecular breeding objectives towards crops displaying healthy attributes), which is complementary to an important objective of the Agriculture and Fisheries Research Programme. A typical project will attempt to achieve the appropriate level of integration of plant science with end-user technology, and of target-oriented research with those areas of eukaryotic biology where key knowledge is stemming from (genome analysis, structural analysis of macromolecules and enzymes, signalling pathways, bio-informatics, etc.).

Animal physiopathology

Genetic linkage maps of the genomes of farm animals have already been completed, in particular under the earlier Bridge Programme. Gene mapping will be very useful to select animals for traits which are under the control of many genes (quantitative trait loci or QTL) such as the resistance to diseases, to eliminate genes with harmful effects or to transfer new genes of interest from various strains of animals by appropriate breeding. European networks will be established or extended to map the genomes of animals chosen for their agricultural or industrial importance. Such studies will greatly advance our knowledge on QTL analysis. Research activities on reproductive mechanisms of the farm animals will also be supported due consideration being given to animal welfare and animal genetic diversity principles.

It is essential for the understanding and control of severe human and animal diseases to develop transgenic and other animal models. Studies will be conducted to allow the development of new techniques to raise animal models with precise and predicted genetic characteristics designed to provide information of high quality and specificity in relation to pathological disorders. Research will be encouraged where it produces evidence on the physiological roles of regulated/deregulated pathways, or genetically-encoded factors during the evolution of any particular disease.

An equally important objective will be the development of new methods for somatic gene therapy, particularly vectors complementing weakened or missing gene functions potentially of medical importance. The programme will also consider other associated techniques to overcome barriers precluding the general applicability of somatic gene therapy protocols, with regard to recipient cells. Models which could be used for the evaluation of the method will also be considered.

Concerning the last two subjects which might impinge on future medical and veterinary applications, the emphasis of this programme will remain on the design and development of experimental tools giving rise to possible synergies with the Biomedical and Health or Agriculture and Fisheries Research Programmes.

Area 4: Cell communication in neurosciences

Cellular biology, molecular biology including molecular genetics and biochemistry, pharmacology will be combined with genetic engineering in order to promote multidisciplinary studies on cell physiology and cell communication of the nervous system and with a view to promoting neurosciences using the support of these disciplines. Special attention will be paid to the physiology of the development of the nervous system, the management of information (intra- and intercellular events) by the nervous cells, possible cellular dysfunctions such as those associated with human and animal degenerative diseases, the design of neurodrugs taking advantage of biotechnology, the development of in vitro tests for the pharmaco/toxicology of such substances.

Projects including definite steps towards a medical or a veterinary application would be regarded as better placed within the Biomedical and Health or the Agriculture and Fisheries Research Programme, whereas this programme tends to concentrate on approaches at molecular and cellular levels and the development of tools necessary for such detailed investigations.

The four actions above will benefit from a range of specific measures aiming at the achievement of increased harmony between scientific progress and realities of the economic world, namely: the systematic combination of advanced biotechnology with the whole spectrum of established disciplines and techniques, to increase the control which the practitioner may have over biological processes; the close interaction of scientific teams with the users of research results and with expert groups looking into new indicators of welfare; the accompanying assessment of lateral effects which arise with the recognition of economic and social constraints (provisions for safety, ethical issues, education, public information, targeted training to link research and industry).

OBJECTIVES ADDRESSED BY CONCERTATION

Four other activities will be approached by setting up research projects or concertation networks. The objective in this case will be to share work and information in fast-moving fields, and to pool data or methods which may provide useful bases upon which science policy and regulatory measures could be developed further.

Area 5: Immunology and trans-disease vaccinology

In immunology, new biotechnology-derived substances in relation with the immune system (monoclonal antibodies, cytokines, growth factors, receptors, adhesion molecules etc.) may reveal a range of effects preventing or controlling major human and animal pathologies. Special attention will be given to the possibility to initiate mechanistic studies of the interaction of these substances with the physiology of the organism, in order to develop new pharmacological concepts which should be relevant to specific interests of the Biomedical and Health Research Programme.

Research on trans-disease vaccinology will be organized across Europe (live vectors for vaccines, their ability to induce immunity to normal or pre-immunised organisms, their safety in normal, immunocompromised hosts and in other species likely to be in contact - antigen delivery systems, particularly those giving the possibility to administer a unique dose - mucosal and peroral vaccination - induction of T and/or B immune responses, etc.). Model diseases used for the demonstration of the new methods will have to be chosen for their importance in human or veterinary medicine.

Area 6: Structural biology

The systematic determination of the three-dimensional structures of biomolecules will contribute to the knowledge of the relationships between primary structures and the tertiary structures of biologically active macromolecules and, even more, the quaternary structures of the multi-subunit complexes which mediate most biological activities. The accelerating accumulation of structural information underlines the need to store, retrieve and analyze this information (see Infrastructures).

The objective is the understanding of the structural basis of biomolecules and complexes (proteins, DNA, RNA, carbohydrates and lipids) which is essential to the discovery and refinement of new biochemical entities. The improvement of the resolution of the techniques and the growing size of structures that they can assess will be crucial. Such technical developments will allow work on subcellular structures, e.g., chromosomes, splicesomes, replisomes, with further implications for biological understanding.

Biological macromolecules that catalyze chemical reactions (enzymes, abzymes, ribozymes) are particularly of interest for industry. To obtain biocatalysts with new properties, two different and complementary ways are to be considered. The first is the rational design of biomolecules which requires a detailed understanding of, and control over biomolecular conformation and reactivity (position of functional groups, folding properties). The second way is in vitro directed molecular evolution. This technology useful alternative to true design consists of a large, heterogeneous pool of biomolecules subjected to multiple rounds of selection, amplification and mutation, and leading to biomolecules with the desired properties. RNA, acting as both a genetic message and an enzyme, are ideal molecules for the type of in vitro evolution experiments which are invited.

Finally, the emerging interface of biology and electronics will be stimulated with a view to allowing the integration of competences in structural biology, molecular engineering and nanolithographic patterning towards new possibilities of designing functional units which could incorporate modifications at the scale of the nanometre.

Area 7: Pre-normative research, biodiversity and social acceptance

Community efforts will be brought into closer harmony with national efforts when this leads to methods or data that would consolidate the rational basis of regulatory approaches and would support the development of internationally accepted standards and systems of risk assessment. This activity will be encouraged in three fields: the development of toxicological/pharmacological in vitro tests, the biosafety evaluation of biotechnology-derived products, and the development of processes solving environmental problems.

As far as in vitro testing is concerned, priority interest will be in neurobiology, immunology and developmental pharmaco/toxicology as well as in the development of cultures or co-cultures of cells maintaining their normal metabolism, with a clear view to providing methods and data usable as alternatives to animal testing and eventually made available for prevalidation studies, such as the Biomedical and Health Research Programme has planned.

As far as the biosafety evaluation of transgenic organisms and derived products is concerned, special emphasis will be given to the risks possibly associated with releases of genetically modified organisms, including recombinant life vaccines, into the environment and to the scientific support to the implementation of the Community's regulatory framework ensuring safety for man and the environment.

This should be approached at two levels. First at the basic level of molecular ecology and, second, at the level of prenormative research, which gathers data of particular usefulness to regulatory authorities when carrying out risk assessments under Community legislation.

Most of these studies, and particularly prenormative research, should be complemented by field tests in order to take into consideration environmental factors.

Microbial ecology does not only serve prenormative research but it is an indispensable element for studies on environmental biotechnology and microbial biodiversity.

In order to lead environmental biotechnology to useful results, knowledge acquired from microbial ecology, microbial diversity and bioprocessing (see cell factories) should be appropriately combined, aiming at the prevention, detection of hazardous compounds and the remediation of the environment.

Microbial diversity should be better understood, with particular attention to microbial characterization in extreme habitats, isolation strategies and cultivation procedures, direct analysis of microbial communities through DNA sequencing, biosystematics using molecular techniques and markers, screening strategies and conservation.

Plant and animal diversity studies will also be part of the more general approach which consists in using molecular and cellular biology to bring about methodological improvements for the conservation of genetic resources or/and for exploring unexploited diversity.

Particular emphasis will be put on analyzing lateral issues such as public perception and the acceptance of biotechnology in general, in liaison with the horizontal activity on ethical, social and legal aspects of the life sciences and technologies, taking into account the European Bioethics Convention and environmental aspects.

Area 8: Infrastructures

Development of bio-informatics, of information infrastructures and resource centres (databases, biological collections, etc.) as a service and support to wider scale research by the Community or its Member States. The services shall aim to support and underpin the overall objectives of the Biotechnology Programme, particularly in the areas of genome sequencing, structural biology and biodiversity. Special attention shall be paid to ensure that these services match the research needs, including those of large industry and SMEs.

Necessary actions should be taken as to ensure proper publicity and wide spread distribution of collections and information contained in databases. In the case of biological collections, coupling of specimen distribution channels and related Information Systems will be fostered in order to ease access to repository catalogues and eventual ordering and delivery.

Large scientific and technical communities should be able to have simple and, as far as possible, unique access to deposit and retrieve information from diverse source of data, including bibliographic indexes. To achieve these objectives, following facilities should be provided by the information services: user-friendly interfaces; cross-reference and navigation mechanisms between data entries; interconnection of diverse national and Community-wide databases via European networks; extensive use of standards and, when necessary, definition of new exchange formats. Close cooperation with existing R& D programmes in the field of Information Technologies should be encouraged in order to benefit of their findings and achievements.

Research activities on novel bio-informatics technics will be supported whenever they could contribute to improve the service aspect of the mentioned tasks.

OBJECTIVES TREATED BY MEANS OF HORIZONTAL ACTIVITIES

Demonstration activities in biotechnology

New biotechnologies stemming from forefront European research encounter specific difficulties and socio-economic barriers which preclude their full exploitation in the market place. European biotechnology researchers continuously produce a rich flow of opportunities that can benefit society in many different ways. However, a variety of techno-economic uncertainties, inherent to the adoption of these complex interdisciplinary processes (which are not easily understood by the technology users, or even, in some way or another, feared by the public), hamper the full exploitation of research efforts and increase the time and risks involved in the marked penetration of well established, new biotechnological concepts. Community support to carefully selected biotechnology demonstration activities will encourage European concerns to deploy the costly, critical-mass, interdisciplinary resources needed for overcoming those hurdles and will, therefore, facilitate the adoption of new biotechnologies by potential users in industry and services.

Biotechnology demonstrations can be linked to any scientific and technological research area considered within this specific programme and will be developed in close cooperation and synergy with the Agriculture and Fisheries, and the Biomedical and Health Research Programmes, integrating resources from all disciplines relevant to project implementation. A high thematic flexibility is needed for the bottom-up identification of demonstration activities from which the highest impact is to be expected, both in strengthening the competitiveness of European industries, and in promoting an objective public understanding of biotechnology. Particular focus areas might include, amongst others: novel cell technology and biochemical engineering approaches with the potential to maximize benefits from the cell factories; new vaccines; use of transgenic plants and animal models; bio-remedial application of micro-organisms for the removal of toxic wastes.

Ethical, social and legal aspects (ESLA)

The participation of the Community in a dialogue embracing all relevant socio-political and bioethical positions, taking into account cultural differences and existing national policies will be encouraged and, where appropriate, deliberately organized. Whilst recognizing existing national and international points of view, scientific studies will focus on transdisciplinary approaches of selected topics, of high relevance and possible impact within the biotechnology programme, and on the applications of their results (e.g. genome research, biodiversity, intellectual property, in particular research exemption for patents, introduction of new biotechnology products for industry and environment, transgenic animals, neurosciences). Where appropriate, these activities will also contribute to identifying areas for the application of common principles - the draft European Bioethics Convention of the Council of Europe will be taken into account - and for agreeing their best possible interpretation. The continuous updating of scientific data in support to regulatory processes will be facilitated.

Public perception

Specialized working groups will be established to prepare ad hoc initiatives, like workshops, conferences, reports and surveys important for the public perception of biotechnology. Appropriate and timely information about research objectives, scientific breakthroughs, knowledge obtained, obstacles are the key elements for the public perception of biotechnology which must be reviewed in an open discussion about possible applications and implications of the results of this new technology. It is important that in addition to information dissemination, in particular through conferences and surveys, it could be demonstrated that suggestions and concern expressed from the public side are considered in strategic planning.

Socio-economic impacts

An important factor for the competitiveness of European industry and employment will be the adoption of up-to-date and sustainable production systems. Consequently the opportunities offered by biotechnology will be promoted. In large industrial areas (agro-industry, pharmacy, fine chemicals etc.) while new products and productions tend to be based on biotechnological research (for example new pharmaceuticals), the actual production will rely in general on traditional technologies. Efforts will be made to assess these indirect effects of the biotechnology research programme, by which new tools and methods get amalgamated with an existing background of established practices, to the benefit of industrial branches already in place. At the same time, questions will be asked on the rise of new industrial sectors based on opportunities offered to research SMEs, and on the specific related handicaps/chances experienced in Europe.

ANNEX II

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ANNEX III

RULES FOR IMPLEMENTING THE PROGRAMME

1. The detailed rules for the Community's financial contribution are laid down in Annex IV to the Decision on the fourth framework programme.

The detailed rules for the participation of undertakings, research centres and universities, and for the dissemination of results will be laid down in the measures provided for by Article 130 j of the Treaty.

However, for the purpose of implementing this programme, the following exceptions shall apply:

1.1. Participation in this programme is open, with financial support from the Community:

(a) to all legal entities, established and regularly carrying out RTD activities

- in the Community, or

- in a third country associated, wholly or in part, with the implementation of the relevant programme through an agreement concluded between the Community and the said third country

(b) to the Joint Research Centre.

1.2. Participation in this programme is open, without financial support from the Community, and on condition that their participation is in the interests of Community policies:

(a) to legal entities established in a country which has concluded a scientific and technical cooperation agreement with the Community relating to activites covered by the programme, provided the participation accords with the terms of the agreement,

(b) to legal entities established in a European country,

(c) to international research organizations.

1.3. The participation of European international organizations may be financed on the same basis as that for Community organizations in duly specified cases.

2. This programme will be carried out through indirect action, whereby the Community makes a financial contribution to RTD activities carried out by third parties or by JRC institutes in association with third parties:

2.1. Shared-cost activities covering the following means of action:

- RTD projects carried out by undertakings, research centres and universities, including consortia for integrated projects with a common objective;

- basic research projects within thematic networks to be established, based on generic technologies of strategic importance, involving industrial companies, research centres and universities;

- technology stimulation to encourage and facilitate participation by SMEs by granting an award covering the exploratory phase of an RTD activity, including the search of partners, and via cooperative research. The award will be granted following the selection of outline proposals which may be submitted at any time.

- support for the financing of infrastructure or facilities necessary for the performance of a coordination action (reinforced coordination activity)

- demonstration activities, as defined in Annex III of the Framework Programme, which may include feasibility awards and direct grants to technologists, intended to overcome specific hurdles preventing utilization of new technologies and to build bridges between producers and technology users.

2.2. concerted actions, which coordinate, in particular through concertation networks, RTD and demonstration projects already funded by public authorities or private organizations. The concerted actions may also perform the coordination needed for thematic networks which, through RTD shared cost actions (cf. 2.1, first indent), bring together producers, users, universities and research centres to focus on the same technological or industrial goal.

2.3. specific measures, such as those encouraging standardization, and those measures intended to set up general service tools for research centres, universities and firms. The Community contribution may be up to 100 % of the costs of these measures.

2.4. Preparatory, accompanying and support measures, including the following types:

- studies in support of this programme and in preparation of possible future actions;

- conferences, seminars, workshops or other scientific or technical meetings, including intersectorial or multidisciplinary coordination meetings;

- use of external expertise, including access to scientific data bases;

- scientific publications, including dissemination, promotion and exploitation of results (in coordination with the activities carried out in the Third Action);

- assessment studies of socio-economic implications and also of possible technological risks associated with all projects of this programme in coordination with the programme Targeted socio-economic research;

- training activities linked to the research carried out under this programme;

- independent evaluation (including studies) of management and results of programme activities;

- measures in support of the operation of networks to provide information and decentralized assistance to SMEs in coordination with the Euromanagement auditing activity of RTD.

The dissemination and exploitation of results obtained in this programme will be complementary to those carried out by the Third Action and will be implemented in close coordination with it. The networks of partners of RTD projects are the principal mechanisms for dissemination and exploitation of results. They will be reinforced with publications, conferences, promotion of results, studies of the techno-economical potential, etc. In order to ensure optimal exploitation all those factors which may facilitate the utilization of results will be considered at the start of the RTD projects and whilst they are in progress.