- Email: [email protected]
European laboratories without walls: focused precompetitive research
TIBTECH - D E C E M B E R 1987 [Vol. 5]
structures are being determined each year. As new ones are published, one looks keenly to see how they fit into the emerging picture, and in what ways the new data allow us to test, probe, and extend our current ideas. Against this background, several projects at EMBL are aimed at the analysis of known sequences and structures to elucidate basic principles. Looking towards the future, these will, sooner or later, support serious attempts to move to the ultimate goal of predicting tertiary structures of proteins from amino acid sequence alone. Specific projects include: •
in methods of prediction of secondary structure from sequences, the analysis of newly determined gene sequences, and the search for 'fingerprints' by which structures and functions may be recognized from amino acid sequences. Analysis of known structures: the course.~and mechanism of evolution in protein families (how can very different amino acid sequences produce similar structures?), and mechanisms of conformational change. Protein design (this is the inverse of the folding problem - in protein design one starts with a target structure in mind and tries to suggest an amino acid sequence that might form it): This involves im-
Sequence-structure correlations: the conformational variation of individual oligopeptides found in native structures, improvements []
[]
[]
[]
[]
[]
[]
[]
[]
[]
European Laboratories Without Walls: focused precompetitive research Robert van der Meer, Etienne Magnien and Dreux de Nettancourt The most striking aspect of biotechnological research in Europe is its vitality, which springs from the variety and diversity of the subjects studied and the approaches adopted. Over the last few years, many countries in Europe have accorded high priority to biotechnology in their national R & D stimulation programmes, with the result that there has been a significant growth in biotechnological research. In many subject areas, however, fragmentation of research among Robert van der Meer is at the HOM business and venture development, Hollandse Ontwikkelings Maatschappij voor bedrijven by, Scheveningseweg 9, 2517 KS, The Hague, The Netherlands; Etienne Magnien and Dreux de Nettancourt are respectively a member and the head of the Biotechnology Division at The Comm&sion of The European Community, DG XII for Science, Brussels, Belgium.
member states can result in duplication of effort. Individual national projects can be condemned to isolation and relative insignificance. In order to solve this problem, the Commission of the European Communities (CEC) has set up research and training programmes to underpin existing achievements and eliminate weak points. The Commission's R & D programmes are intended to improve the international competitiveness of European industry and agriculture while increasing environmental awareness. They must also complement national initiatives. Therefore, calls for research proposals for the Community programmes BEP and BAP* stipulated transnationality of joint projects as the main criterion of acceptability. Consequently, transnational cooperation in European biotechnology is now a reality. Many of the BAP
© 1987, Elsevier Publications,Cambridge 0166-9430/87/502.00
proved methods of prediction of structure from sequence, collaboration with experimental groups in planning modifications of known proteins, and the prediction of novel proteins with new functions or structures. Protein design was the subject of a major international workshop held at EMBL in 1986. An amino acid sequence devised during that workshop - a modification of the protein ROP - is now being synthesized at the Gesellschaft ffir Biotechnologische Forschung (GBF) in Braunschweig, FRG. Compiled by
ARTHUR
EMBL, Meyerhofstrasse Heide}berg, FRG. []
[]
[]
M. LESK
1,
6900
[]
projects involve more than two laboratories (Table 1). From the outset, all the cooperative projects distributed tasks among laboratories in different Member States. Now, where the competitive advantage of integrated work under the Community programme has become particularly obvious, multidisciplinary collaborative associations have been brought into being. These are the European Laboratories Without Walls (ELWWs). An ELWW is larger than a simple cooperative project, but smaller than a research programme. It is an openended, transnational association of cooperating European groups with a common commitment to targetoriented multidisciplinary research. With their origin in the biotechnology R & D programmes of the CEC, the ELWWs are clearly European in character. But what of 'laboratories without walls'? From the outset it has been stressed that these associations are open to any researcher with either an industrial or a university background who can contribute usefully *Biomolecular Engineering Programme (1982-1986) and Biotechnology Action Programme (1985-1989), respectively; for a more detailed description, see Trends in Biotechnology (1987) 4, 277.
TIBTECH - DECEMBER 1987 [Vol. 5]
Genetic engineering of dairy starter cultures i~ Goals To devise genetic techniques for application to : ~ ..... lactic streptococc= in order to develop superior strains for dairy fermentations. To develop vector systems and transformation techniques of bacteriophage-host interactions, cloning and the characterization of proteinase activities.
Participants Ch. Daly, (Eire), M. J. Gasson, (UK), M Teuber, (FRG), W. M de Vos and G. Venema (The Netherlands)
Expertise
Strain selection, the genetic improvement of starters cultures, resistance to phase infections; the molecular biology of proteases and flavours.
Achievements The discovery of a Streptococcus cremoris ptasmid that also replicates in E. coil. The isolation of highly phage resistant strains and the cloning of phage-resistance genes from resistanceassociated plasmids. The cloning of the proteinase region, and the discovery of a demethiolase enzyme with prospects for accelerating cheese ripening.
Molecular genetics of mitochondrla in relation to crop improvement Goals
To understand the structure and expression of the mitochondrial genome and of its recombinational mechanisms to devise vectors of general applicability to the transformation of mitochondria.
Participants
M Briquet, (Belgium), A.
Cornu, F. Quetier, (France), A.P. Czernilofsky, (FRG), D. R. Davies and C. J. Leaver (UK), H. J. J. Nijkamp, (The Netherlands).
Expertise
Structure/ expression studies of the mitochondrial genome of major crop plants, methods of mitochondrial transfer (fusion, microinjection, wide-ranging sexual crosses), characterization of native plasmids and construction of synthetic plasmids for transformation purposes.
Achievements
Elucidation of the molecular basis of cytoplasmic male sterility; -" described recombinational events in mitochondria giving rise to aberrant reading 4-rames. Accumulating knowledge of the mitochondrial genome.
Molecular genetics of phytopathogenic Erwiniae Goals Understanding the utilization of plant cellulose and pectin by Erwinia m the course of the plantpathogen interaction: production of anti-tumoral enzymes; construction of secretion vectors for the production of engineered polypeptides; exploitation of Erwinia pectinase/cellulase genes to increase substrate utilization of industrial microbes; identification of mechanisms underlying plant phytopathogenicity.
Participants
J.P. Chambest, A. Kotoujansky and J.M. Robert-Baudouy, (France), G.P.C. Salmond, (UK), A. Toussaint-Pourbaix, (Belgium)
Expertise Plant pathology, biochemistry, enzymology and molecular genetics. Achievements The cloning of genes involved in cellulolysis and pectinolysis; characterization of mutations inhibiting secretion of both pectinase and cellulase with a view to studying secretion mechanisms in Gram negative bacteria; analysis of phytopathogenicity; avirulent mutants were shown to have altered lipopotysaccharide (LPS) profile and in proteins associated with iroh transport.
In-vitro cell manipulation of crop species
Goals The genetic manipulation of four economically important crop plants by means of an array of methods for the transfer of genetic elements and complexes varying from cloned DNA fragments to complete nuclei or chromosomes.
Participants M.G.K. Jones, (UK), M. J. Tempelaar and L. van Vloten-Doting, (The Netherlands), M. Jacobs/ I. Negrutiu, (Belgium), F. Sala, (Italy), M. Caboche and Y. Dattee (France), H. Lerz. (FRG)
Expertise
Characterization of selectable mutants, synchronization of the cell-cycle, cellmediated gene transfers, chromosome-, DNAand liposome-mediated gene transfers, cytological and molecular analysis of transformants and regeneration techniques.
Achievements Production of new hybrid plants from Solanum tuberasum and Solanum brevidens (potato) through electrofusion; the application of y-fusion to the production of asymmetric hybrids, e.g. combinations of Nicotiana plumbagimfoil and Atropa belladonna or Beta spp. Transformations of cereal protoplasts with transient expression of the reporter genes have also been repeatedly achieved.
TIBTECH - DECEMBER 1987 [Vol. 5]
--Table 2
Industrial affiliation of BAP projects in the different research s e c t o r s N u m b e r of
Number of companies Sector
to the collective activity. Thus ELWWs are not exclusive clubs, although the intention is to involve as many top-ranking research scientists as possible in their work. Participation by industry is usually welcomed. Figure 1 indicates how four of the ELWWs have operated. To address specific goals within an area of technology, expertise and resources from several laboratories have been harnessed. Although one can never know what might have happened without ELWWs, the list of their achievements to date indicates the effectiveness of collaborative research on this scale.
Industrial
interested
contractors*
in sector
projects
Bioinformatics Biotic materials
4:42 0:13
19 7
12 5
8 5
4:45 4 : 64 1 : 35 0 :7 3 : 40 0 : 16
35 43 31 5 19 10
17 23 13 3 16 6
14 20 12 1 14 3
16:262
169
95
77
Subprogramme II Enzyme engineering P l a n t cells
Microorganisms Risk a s s e s s m e n t Animal cells In vitro t o x i c i t y
Total *Number
o f i n d u s t r i a l c o n t r a c t o r s : total number of contractors
provide combinations of skills rarely available within the confines of an individual university, institute or company.
Information exchange and technology transfer- Participation in ELWWs of leading scientific groups has led to increased exchange of information: healthy competition between national groups has been superseded by healthier collaboration. The dissemination across state boundaries in Europe of the views of experts will now more readily influence the direction of n e w avenues of research. Open and rapid transmission of biological data and materials have been facifftated by ELWWs as has the exchange of scientific staff involved in highly innovative experiments. They also provide a platform for information
1
funded
under
the
Biotechnology
Action
Number of participating laboratories
Contextual measures Enzyme engineering
Genetic engineering of agricultural species Genetic e n g i n e e r i n g o f i n d u s t r i a l microbes Risk a s s e s s m e n t G e n e t i c engineering of animal husbandry/novel m e t h o d s a n i m a l cell cultures In vitro e v a l u a t i o n o f t o x i c i t y and pharmacological activity of molecules Total
interested
C o n t e x t u a l measures
The integration of work is more apparent in ELWWs than in the original bilateral collaborations of BAP and BEP. Three facets of this integration are particularly noteworthy: information from the forefront of research is circulated freely; there is a iramework for the continuous exchange of materials, data and staff; and there is regular joint planning and evaluation of experiments. D i v e r s i t y - Input from various European countries gives ELWWs a variety of research approaches and expertise across a wide range of disciplines. This particularly benefits biotechnology since ELWWs can Number of projects Programme (BAP)
in w h i c h i n d u s t r y is
Subprogramme I
Fruits o f integration
~Table
projects Total number of
1
2
3
4
5
1 1 -
7 8 15
-
4 4 2
4
-
6
6
-
1
2 7
1 5
-
-
4
1
-
3
49
19
4 2
11
Total
3
1 1
17 17 23
1
-
13
2
-
3 16
1
-
6
11
2
95
-
1
6andover
exchange and technology transfer between academics and with interested industrialists. Each ELWW addresses the complexity of scientific and industrial structures in different member states and attempts to overcome the physical and psychological barriers to horizontal (between disciplines) and vertical (between academia and industry) technology transfers. It is, perhaps, less likely that European biotechnological discoveries will be exploited only on some other continent. Catalysis of research - Through limited funding under BEP or BAP (approximately one researcher plus operating costs for each participating laboratory), the skills of highly qualified research groups are merged in functional, target-oriented cooperative projects. Thus the funds act catalytically, guiding and tuning the research work performed. It is research strategies and not just individuals which benefit. Moreover, the distribution of tasks among the European member states can help in harmonization of national stimulation programmes. There is a degree of overlap between ELWWs, especially where techniques are shared. This results in further cross-fertilization between disciplines and applications giving additional impetus to scientific and technological progress. Size a n d l i f e t i m e o f an ELWW The level of participation in ELWWs (3-12 participants) is easily manageable. Research can be coordinated for optimum efficiency and scientific productivity and for
TIBTECH - DECEMBER
1987 [Vol. 5]
-- Fig. 2
Precompetitive loose associations of academic laboratories
Stratiffed in volvement o f industry
the exchange of techniques, results and people. The lifetime of ELWW is the period required to attain the common scientific objective for which it was set up. It is dissolved if this objective proves to be unattainable or if the research has been brought to a successful conclusion. If new avenues for further development are opened, an ELWW will cease to exist. It becomes split into narrower associations based on direct bilateral, contractual agreements with interested firms, Industrial interest in ELWWs
Many academic research groups in biotechnology have contacts with one or more companies. The creation of an ELWW, therefore, can widen the interest and involvement of European industry, perhaps initially without much in the way of contractual commitment. How should industry's involvement be developed further? As yet there is no precedent for evolution of an ELWW into a series of bilateral contracts with European firms. At Commission level, this question is being discussed by the Management and Coordination Advisory Committee (CGC) on Biotechnology and Working Party 5 of the Industrial Research and Development Advisory Committee (IRDAC) and also at industrial round table meetings with various firms that have expressed their interest in projects implemented under the BAP. Industry has indicated considerable interest in the BAP, and provides written (and sometimes more concrete) support for the research projects in progress, frequently hiring scientific staff initially from contracting laboratories (Table 2). Many firms have attended the contractors' meetings recently organized by the Commission which marked the start of the BAP projects. It is important for interested firms to be able to monitor the progress of cooperative research in the ELWWs.
Ideally, each ELWW should have its counterpart in the industrial community; a group of firms prepared to explore commercial prospects in the relevant areas. Any research results with commercial possibilities could thus be transferred effectively to industry. In turn, the industrial partners can steer the ELWW along lines of strategic interest towards important commercial breakthroughs. For the time being, however, the strategic research in ELWWs will continue to be directed largely towards precompetitive generic technologies. In certain cases, the cooperation between firms and ELWWs could benefit from having a legal basis, addressing questions of cooperation between firms, and between firms and their academic partners. A legal framework recently devised by the Commission for 'European Economic Interest Groupings' might serve as a model for enhancing the relationship between the European biotechnological industry and the R & D infrastructure. Both the CGC on Biotechnology and the Commission will strive to establish effective links between the ELWWs and the European biotechnological industry so that the research results obtained under the BAP can more easily reach the targets for which the programme was set up. To
this end, it is recommended that a stratified form of research partnership (Fig. 2) be adopted. Two aspects of this stratified involvement are important. Firstly, ELWWs are destined to be replaced by narrower industrial agreements when firms become sufficiently interested. Hence there is a need for industry to be involved at an early stage. Secondly, ELWWs simple constitute one layer in the stratified research partnership: a motherlayer which gives birth to new ideas and developments in response to real industrial requirements and continuously feeds the layers represented by company-based industrial research. In short
• ELWWs should initially deal with precompetitive research subjects, addressing limiting factors such as methodological bottlenecks or gaps in knowledge. • ELWWs must be open-ended to facilitate joint experiments and the exchange of forefront information and researchers. • There must be mechanisms for dissociation of ELWWs into smaller units for competitive industrial development projects when the transition from basic to applied research has taken place. • Each ELWW should be backed up by its counterpart in industry. In this connection, closer attention should be paid to the organizational structure of and the legal basis for such groups.
m Haemophiliaand biotechnology
[] Recombinant virus vaccines m The future ofar~imal cell cuFture
m Secondgeneration monoclonal antibodies
n Growthhormone m C r o s s f l o w filtratTon
structures are being determined each year. As new ones are published, one looks keenly to see how they fit into the emerging picture, and in what ways the new data allow us to test, probe, and extend our current ideas. Against this background, several projects at EMBL are aimed at the analysis of known sequences and structures to elucidate basic principles. Looking towards the future, these will, sooner or later, support serious attempts to move to the ultimate goal of predicting tertiary structures of proteins from amino acid sequence alone. Specific projects include: •
in methods of prediction of secondary structure from sequences, the analysis of newly determined gene sequences, and the search for 'fingerprints' by which structures and functions may be recognized from amino acid sequences. Analysis of known structures: the course.~and mechanism of evolution in protein families (how can very different amino acid sequences produce similar structures?), and mechanisms of conformational change. Protein design (this is the inverse of the folding problem - in protein design one starts with a target structure in mind and tries to suggest an amino acid sequence that might form it): This involves im-
Sequence-structure correlations: the conformational variation of individual oligopeptides found in native structures, improvements []
[]
[]
[]
[]
[]
[]
[]
[]
[]
European Laboratories Without Walls: focused precompetitive research Robert van der Meer, Etienne Magnien and Dreux de Nettancourt The most striking aspect of biotechnological research in Europe is its vitality, which springs from the variety and diversity of the subjects studied and the approaches adopted. Over the last few years, many countries in Europe have accorded high priority to biotechnology in their national R & D stimulation programmes, with the result that there has been a significant growth in biotechnological research. In many subject areas, however, fragmentation of research among Robert van der Meer is at the HOM business and venture development, Hollandse Ontwikkelings Maatschappij voor bedrijven by, Scheveningseweg 9, 2517 KS, The Hague, The Netherlands; Etienne Magnien and Dreux de Nettancourt are respectively a member and the head of the Biotechnology Division at The Comm&sion of The European Community, DG XII for Science, Brussels, Belgium.
member states can result in duplication of effort. Individual national projects can be condemned to isolation and relative insignificance. In order to solve this problem, the Commission of the European Communities (CEC) has set up research and training programmes to underpin existing achievements and eliminate weak points. The Commission's R & D programmes are intended to improve the international competitiveness of European industry and agriculture while increasing environmental awareness. They must also complement national initiatives. Therefore, calls for research proposals for the Community programmes BEP and BAP* stipulated transnationality of joint projects as the main criterion of acceptability. Consequently, transnational cooperation in European biotechnology is now a reality. Many of the BAP
© 1987, Elsevier Publications,Cambridge 0166-9430/87/502.00
proved methods of prediction of structure from sequence, collaboration with experimental groups in planning modifications of known proteins, and the prediction of novel proteins with new functions or structures. Protein design was the subject of a major international workshop held at EMBL in 1986. An amino acid sequence devised during that workshop - a modification of the protein ROP - is now being synthesized at the Gesellschaft ffir Biotechnologische Forschung (GBF) in Braunschweig, FRG. Compiled by
ARTHUR
EMBL, Meyerhofstrasse Heide}berg, FRG. []
[]
[]
M. LESK
1,
6900
[]
projects involve more than two laboratories (Table 1). From the outset, all the cooperative projects distributed tasks among laboratories in different Member States. Now, where the competitive advantage of integrated work under the Community programme has become particularly obvious, multidisciplinary collaborative associations have been brought into being. These are the European Laboratories Without Walls (ELWWs). An ELWW is larger than a simple cooperative project, but smaller than a research programme. It is an openended, transnational association of cooperating European groups with a common commitment to targetoriented multidisciplinary research. With their origin in the biotechnology R & D programmes of the CEC, the ELWWs are clearly European in character. But what of 'laboratories without walls'? From the outset it has been stressed that these associations are open to any researcher with either an industrial or a university background who can contribute usefully *Biomolecular Engineering Programme (1982-1986) and Biotechnology Action Programme (1985-1989), respectively; for a more detailed description, see Trends in Biotechnology (1987) 4, 277.
TIBTECH - DECEMBER 1987 [Vol. 5]
Genetic engineering of dairy starter cultures i~ Goals To devise genetic techniques for application to : ~ ..... lactic streptococc= in order to develop superior strains for dairy fermentations. To develop vector systems and transformation techniques of bacteriophage-host interactions, cloning and the characterization of proteinase activities.
Participants Ch. Daly, (Eire), M. J. Gasson, (UK), M Teuber, (FRG), W. M de Vos and G. Venema (The Netherlands)
Expertise
Strain selection, the genetic improvement of starters cultures, resistance to phase infections; the molecular biology of proteases and flavours.
Achievements The discovery of a Streptococcus cremoris ptasmid that also replicates in E. coil. The isolation of highly phage resistant strains and the cloning of phage-resistance genes from resistanceassociated plasmids. The cloning of the proteinase region, and the discovery of a demethiolase enzyme with prospects for accelerating cheese ripening.
Molecular genetics of mitochondrla in relation to crop improvement Goals
To understand the structure and expression of the mitochondrial genome and of its recombinational mechanisms to devise vectors of general applicability to the transformation of mitochondria.
Participants
M Briquet, (Belgium), A.
Cornu, F. Quetier, (France), A.P. Czernilofsky, (FRG), D. R. Davies and C. J. Leaver (UK), H. J. J. Nijkamp, (The Netherlands).
Expertise
Structure/ expression studies of the mitochondrial genome of major crop plants, methods of mitochondrial transfer (fusion, microinjection, wide-ranging sexual crosses), characterization of native plasmids and construction of synthetic plasmids for transformation purposes.
Achievements
Elucidation of the molecular basis of cytoplasmic male sterility; -" described recombinational events in mitochondria giving rise to aberrant reading 4-rames. Accumulating knowledge of the mitochondrial genome.
Molecular genetics of phytopathogenic Erwiniae Goals Understanding the utilization of plant cellulose and pectin by Erwinia m the course of the plantpathogen interaction: production of anti-tumoral enzymes; construction of secretion vectors for the production of engineered polypeptides; exploitation of Erwinia pectinase/cellulase genes to increase substrate utilization of industrial microbes; identification of mechanisms underlying plant phytopathogenicity.
Participants
J.P. Chambest, A. Kotoujansky and J.M. Robert-Baudouy, (France), G.P.C. Salmond, (UK), A. Toussaint-Pourbaix, (Belgium)
Expertise Plant pathology, biochemistry, enzymology and molecular genetics. Achievements The cloning of genes involved in cellulolysis and pectinolysis; characterization of mutations inhibiting secretion of both pectinase and cellulase with a view to studying secretion mechanisms in Gram negative bacteria; analysis of phytopathogenicity; avirulent mutants were shown to have altered lipopotysaccharide (LPS) profile and in proteins associated with iroh transport.
In-vitro cell manipulation of crop species
Goals The genetic manipulation of four economically important crop plants by means of an array of methods for the transfer of genetic elements and complexes varying from cloned DNA fragments to complete nuclei or chromosomes.
Participants M.G.K. Jones, (UK), M. J. Tempelaar and L. van Vloten-Doting, (The Netherlands), M. Jacobs/ I. Negrutiu, (Belgium), F. Sala, (Italy), M. Caboche and Y. Dattee (France), H. Lerz. (FRG)
Expertise
Characterization of selectable mutants, synchronization of the cell-cycle, cellmediated gene transfers, chromosome-, DNAand liposome-mediated gene transfers, cytological and molecular analysis of transformants and regeneration techniques.
Achievements Production of new hybrid plants from Solanum tuberasum and Solanum brevidens (potato) through electrofusion; the application of y-fusion to the production of asymmetric hybrids, e.g. combinations of Nicotiana plumbagimfoil and Atropa belladonna or Beta spp. Transformations of cereal protoplasts with transient expression of the reporter genes have also been repeatedly achieved.
TIBTECH - DECEMBER 1987 [Vol. 5]
--Table 2
Industrial affiliation of BAP projects in the different research s e c t o r s N u m b e r of
Number of companies Sector
to the collective activity. Thus ELWWs are not exclusive clubs, although the intention is to involve as many top-ranking research scientists as possible in their work. Participation by industry is usually welcomed. Figure 1 indicates how four of the ELWWs have operated. To address specific goals within an area of technology, expertise and resources from several laboratories have been harnessed. Although one can never know what might have happened without ELWWs, the list of their achievements to date indicates the effectiveness of collaborative research on this scale.
Industrial
interested
contractors*
in sector
projects
Bioinformatics Biotic materials
4:42 0:13
19 7
12 5
8 5
4:45 4 : 64 1 : 35 0 :7 3 : 40 0 : 16
35 43 31 5 19 10
17 23 13 3 16 6
14 20 12 1 14 3
16:262
169
95
77
Subprogramme II Enzyme engineering P l a n t cells
Microorganisms Risk a s s e s s m e n t Animal cells In vitro t o x i c i t y
Total *Number
o f i n d u s t r i a l c o n t r a c t o r s : total number of contractors
provide combinations of skills rarely available within the confines of an individual university, institute or company.
Information exchange and technology transfer- Participation in ELWWs of leading scientific groups has led to increased exchange of information: healthy competition between national groups has been superseded by healthier collaboration. The dissemination across state boundaries in Europe of the views of experts will now more readily influence the direction of n e w avenues of research. Open and rapid transmission of biological data and materials have been facifftated by ELWWs as has the exchange of scientific staff involved in highly innovative experiments. They also provide a platform for information
1
funded
under
the
Biotechnology
Action
Number of participating laboratories
Contextual measures Enzyme engineering
Genetic engineering of agricultural species Genetic e n g i n e e r i n g o f i n d u s t r i a l microbes Risk a s s e s s m e n t G e n e t i c engineering of animal husbandry/novel m e t h o d s a n i m a l cell cultures In vitro e v a l u a t i o n o f t o x i c i t y and pharmacological activity of molecules Total
interested
C o n t e x t u a l measures
The integration of work is more apparent in ELWWs than in the original bilateral collaborations of BAP and BEP. Three facets of this integration are particularly noteworthy: information from the forefront of research is circulated freely; there is a iramework for the continuous exchange of materials, data and staff; and there is regular joint planning and evaluation of experiments. D i v e r s i t y - Input from various European countries gives ELWWs a variety of research approaches and expertise across a wide range of disciplines. This particularly benefits biotechnology since ELWWs can Number of projects Programme (BAP)
in w h i c h i n d u s t r y is
Subprogramme I
Fruits o f integration
~Table
projects Total number of
1
2
3
4
5
1 1 -
7 8 15
-
4 4 2
4
-
6
6
-
1
2 7
1 5
-
-
4
1
-
3
49
19
4 2
11
Total
3
1 1
17 17 23
1
-
13
2
-
3 16
1
-
6
11
2
95
-
1
6andover
exchange and technology transfer between academics and with interested industrialists. Each ELWW addresses the complexity of scientific and industrial structures in different member states and attempts to overcome the physical and psychological barriers to horizontal (between disciplines) and vertical (between academia and industry) technology transfers. It is, perhaps, less likely that European biotechnological discoveries will be exploited only on some other continent. Catalysis of research - Through limited funding under BEP or BAP (approximately one researcher plus operating costs for each participating laboratory), the skills of highly qualified research groups are merged in functional, target-oriented cooperative projects. Thus the funds act catalytically, guiding and tuning the research work performed. It is research strategies and not just individuals which benefit. Moreover, the distribution of tasks among the European member states can help in harmonization of national stimulation programmes. There is a degree of overlap between ELWWs, especially where techniques are shared. This results in further cross-fertilization between disciplines and applications giving additional impetus to scientific and technological progress. Size a n d l i f e t i m e o f an ELWW The level of participation in ELWWs (3-12 participants) is easily manageable. Research can be coordinated for optimum efficiency and scientific productivity and for
TIBTECH - DECEMBER
1987 [Vol. 5]
-- Fig. 2
Precompetitive loose associations of academic laboratories
Stratiffed in volvement o f industry
the exchange of techniques, results and people. The lifetime of ELWW is the period required to attain the common scientific objective for which it was set up. It is dissolved if this objective proves to be unattainable or if the research has been brought to a successful conclusion. If new avenues for further development are opened, an ELWW will cease to exist. It becomes split into narrower associations based on direct bilateral, contractual agreements with interested firms, Industrial interest in ELWWs
Many academic research groups in biotechnology have contacts with one or more companies. The creation of an ELWW, therefore, can widen the interest and involvement of European industry, perhaps initially without much in the way of contractual commitment. How should industry's involvement be developed further? As yet there is no precedent for evolution of an ELWW into a series of bilateral contracts with European firms. At Commission level, this question is being discussed by the Management and Coordination Advisory Committee (CGC) on Biotechnology and Working Party 5 of the Industrial Research and Development Advisory Committee (IRDAC) and also at industrial round table meetings with various firms that have expressed their interest in projects implemented under the BAP. Industry has indicated considerable interest in the BAP, and provides written (and sometimes more concrete) support for the research projects in progress, frequently hiring scientific staff initially from contracting laboratories (Table 2). Many firms have attended the contractors' meetings recently organized by the Commission which marked the start of the BAP projects. It is important for interested firms to be able to monitor the progress of cooperative research in the ELWWs.
Ideally, each ELWW should have its counterpart in the industrial community; a group of firms prepared to explore commercial prospects in the relevant areas. Any research results with commercial possibilities could thus be transferred effectively to industry. In turn, the industrial partners can steer the ELWW along lines of strategic interest towards important commercial breakthroughs. For the time being, however, the strategic research in ELWWs will continue to be directed largely towards precompetitive generic technologies. In certain cases, the cooperation between firms and ELWWs could benefit from having a legal basis, addressing questions of cooperation between firms, and between firms and their academic partners. A legal framework recently devised by the Commission for 'European Economic Interest Groupings' might serve as a model for enhancing the relationship between the European biotechnological industry and the R & D infrastructure. Both the CGC on Biotechnology and the Commission will strive to establish effective links between the ELWWs and the European biotechnological industry so that the research results obtained under the BAP can more easily reach the targets for which the programme was set up. To
this end, it is recommended that a stratified form of research partnership (Fig. 2) be adopted. Two aspects of this stratified involvement are important. Firstly, ELWWs are destined to be replaced by narrower industrial agreements when firms become sufficiently interested. Hence there is a need for industry to be involved at an early stage. Secondly, ELWWs simple constitute one layer in the stratified research partnership: a motherlayer which gives birth to new ideas and developments in response to real industrial requirements and continuously feeds the layers represented by company-based industrial research. In short
• ELWWs should initially deal with precompetitive research subjects, addressing limiting factors such as methodological bottlenecks or gaps in knowledge. • ELWWs must be open-ended to facilitate joint experiments and the exchange of forefront information and researchers. • There must be mechanisms for dissociation of ELWWs into smaller units for competitive industrial development projects when the transition from basic to applied research has taken place. • Each ELWW should be backed up by its counterpart in industry. In this connection, closer attention should be paid to the organizational structure of and the legal basis for such groups.
m Haemophiliaand biotechnology
[] Recombinant virus vaccines m The future ofar~imal cell cuFture
m Secondgeneration monoclonal antibodies
n Growthhormone m C r o s s f l o w filtratTon