- Email: [email protected]
Science funding and infrastructures in Europe
COMMENT
Cancer classification with DNA microarrays
References 1 Wang, D.G. et al. (1998) Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 280, 1077–1082 2 Roberts-Thomson, I.C. et al. (1996) Diet, acetylator phenotype, and risk of colorectal neoplasia. Lancet 347, 1372–1374 3 Kristensen, V.N. et al. (2000) Genetic variants of CYP19
(aromatase) and breast cancer risk. Oncogene 19, 1329–1333 4 Hilgers, W. and Kern, S.E. (1999) Molecular genetic basis of pancreatic adenocarcinoma. Genes Chrom. Cancer 26, 1–12 5 Golub, T.R. et al. (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286, 531–537 6 Galili, N. et al. (1993) Fusion of a fork head domain gene to
Outlook
PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat. Genet. 5, 230–235 7 Alizadeh, A.A. et al. (2000) Distinct types of diffuse large Bcell lymphoma identified by gene expression profiling. Nature 403, 503–511 8 Ross, D.T. et al. (2000) Systematic variation in gene expression patterns in human cancer cell lines. Nat. Genet. 24, 227–235
Science funding and infrastructures in Europe European science in crisis. Scared? Then read on; you should be. I argue that we cannot sit back for much longer and watch our best scientists emigrate to the USA for the most productive part of their career, and that European scientists should not tolerate a funding system that neither rewards an investigator’s brilliance nor the innovative nature of their research. The EC Framework Programme is due for a face lift: scientists should wield the scalpel this time. he year 2000, Europe, the cradle of modern science, the dawning of a new scientific era, and a time to reflect on 400 years of excellence in fields as diverse as mathematics and biology. And what of the future? Well, for many it lies in the USA, because European science, one of our most important domestic products, is still funded and organized piecemeal and unreliably by national research councils, foundations, industry and the European Community (EC). This is particularly true in the life sciences, and is largely owing to the fact that the product of basic research is knowledge, a commodity at once intellectually invaluable and economically valueless without an application. Herein lies the dilemma for policy makers who manage public money. European policy makers have increasingly turned their back on free thought and creative brilliance, and concentrated more on a demand- and applicability-driven scientific culture. Although targeted research is, without doubt, necessary to tackle pressing social demands, basic research, driven primarily by a hunger for knowledge, has given rise to products of spectacular usefulness and completely new fields of research. The value of pure research has long been recognized in the USA, where the wisdom of massive federal investment in basic science is taken for granted. Recent history abounds with examples of socio-economically exploitable discoveries arising from basic research, and who better to promote this idea than scientists? Scientists in the USA do, after all. Indeed, organizations such as the Federation of American Societies for Experimental Biology (FASEB) carry out periodic research into the socio-economical payoffs of investment in basic research. In special features and policy forum articles we are treated to highly persuasive arguments that are supported by numerous examples. For instance, an analysis of the economic impact of monoclonal antibodies1 describes the origin of their development from the fundamental research of immunologists in the 1970s, who wished to understand how the immune system could produce such a large number of different antibodies. This led Köhler and Milstein2,3 to address the problem by developing immortalized cell lines that produced homogenous antibodies to a given antigen
T
0168-9525/00/$ – see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0168-9525(00)02067-9
(myeloma–lymphocyte hybrids). Today, after many years of research and development in different directions, monoclonal antibodies are an invaluable tool in the diagnosis and treatment of disease, not to mention many other non-medical applications. It must be stressed that other basic research in the fields of immunology, oncology, genetics and animal cell culture greatly facilitated the development of monoclonal antibodies. This synergy created by ‘cross-fertilization’ of ideas between different fields of basic research is a fundamental characteristic of the culture of free thinking generated in an unfettered research environment. Further examples of the value of basic research are numerous. The discovery of genetic recombination and the organization of the genetic material of bacteria by Joshua Lederberg opened the way to the production of recombinant proteins, a development of incalculable value. More recently, the study of viral genetics and replication has spawned numerous start-up companies that are concentrating on identifying novel nucleotide analogues as viral reverse transcriptase inhibitors, or peptide-like molecules as viral protease inhibitors. Indeed, the field of molecular biology itself, and its subsequent commercialization in biotechnology, was born out of basic research, the primary aim of which was to increase knowledge. In addition to the economic worth of basic research, the savings to the health system and society in general resulting from the exploitation of basic research discoveries are considerable 4. These range from vaccines and infectious disease treatment to prevention of dental disease. It is, perhaps, because so many advances in healthcare are taken for granted, that their origins in basic research, a practice that has largely remained impenetrable to much of the public, are overlooked. The socio-economic value of basic research is impressively stated in ‘America’s Basic Research; Prosperity Through Discovery’ (http://www.ced.org/pubs/basicresearch.htm), published in 1998 by the Committee for Economic Development (CED). It concludes that basic research in science and engineering, funded predominantly by the federal government, has made a major contribution to the TIG August 2000, volume 16, No. 8
Andrew Moore moore@ embl-heidelberg.de EMBO (European Molecular Biology Organization), Postfach 1022.40, D-69012 Heidelberg, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. 329
Outlook
COMMENT
growth of the US economy (12–25% since the second world war), sowing the seeds for private investment in the exploitation of its results. Furthermore, it recognizes that funding should be allocated purely on merit, regardless of potential applicability of a given area of research. It is no coincidence that the following words were used on the other side of the Atlantic: ‘There is only one proved way of assisting the advancement of pure science – that of picking men of genius, backing them heavily, and leaving them to direct themselves’ [James B. Conant (1893–1978), American chemist, diplomat and educator]. It has long been recognized that this attractive research culture in the USA lures many excellent European minds to the USA, sometimes for ever, and at least for the period in their lives when they are most productive. The relative unattractiveness of Europe is exemplified by the fact that there are twice as many degree-level European students in the USA as American degree-level students in Europe5. Europe’s predicament is further elaborated in a recent document from the European Commission6, which begins with the following statistics: ‘The average research effort in the EC is currently 1.8% of Europe’s GDP, as against 2.8% in the US and 2.9% in Japan’: the trend is towards a greater gap. Furthermore, in the US and Japan, the number of researchers as a proportion of the industrial workforce is more than double that in Europe. These facts have contributed to a trade deficit in hi-tech products of EUR 20 billion per year over the past ten years, a figure that appears to be increasing. However, the established EC funding ethos persists, and by over-concentrating on asking what the needs of society are, is liable to: • over-fund demand-led, short-term science, hence damaging basic research and restricting the pool of ideas from which applications can spring • exclude niche areas which are important to smaller companies • convert the research programme into an instrument for commercial research, which is best funded and performed in a commercial rather than academic context • possibly raise unreasonable hopes for society. For example, society asks for a cure for cancer, but the way towards that is obviously a tortuous and complicated pathway. It is not reasonable to expect to achieve such a goal within the three years of the Programme. The success of science policy in the USA is partly due to political lobbying by scientists. This is accepted as a rightful activity; almost a professional duty. In addition the Internet abounds with US documents analysing the cost:benefit ratio of investment in basic research. A surf through the equivalent European Internet literature leaves one stranded miles from the beach, with no new wave in sight; a new wave is what is needed in Europe, and only scientists can start it. At a meeting last September, scientists from different countries, and European organizations met in Heidelberg under the auspices of the European Molecular Biology Organization (EMBO), and with the support of the Federation of European Biochemical Societies (FEBS), the European Molecular Biology Laboratory (EMBL) and the European Life Scientist Organization (ELSO), to establish the European Life Sciences Forum (ELSF; http://www.elsf.org). The ELSF proposes to advise the EC in the drafting of the sixth (and subsequent) Framework Programme, drawing on the expertise and experience of practising scientists. First among its aims is to convince the EC of the socio-economic 330
TIG August 2000, volume 16, No. 8
Science funding in Europe
value of strong and consistent funding of basic research. This must be accompanied by a more panEuropean approach to research infrastructures and funding in which young investigators receive specific support in establishing research groups and are part of a network. European scientists must follow the example of their American peers and, although it might be considered a dirty word by the more-reserved Europeans, lobby the EC. The advice that the ELSF seeks to offer is the advice of active scientists, who know best how to advance towards scientific or technical goals. They must advise policy makers in the EC (who have the complex, and often underestimated, task of balancing many priorities) where and how to invest their money in order to receive a greater return. European scientists have, in general, abdicated their responsibility, and deprived policy makers of a vital source of advice and information. It is not a simple matter to look into the future and try to predict the socioeconomic outcomes of basic research without the confidence of reliable factual information; but it need not be a matter of blind faith. The ‘short-termism’ generated by the constantly changing criteria for eligibility for a Framework Programme grant makes some areas of research extremely difficult to pursue with continuity and an adequate workforce. This is not to say that applied or socio-economically important research should be replaced by or neglected in favour of research that is less application-driven. It is clearly necessary and desirable to demarcate areas of need, such as cancer, cardiovascular disease and diseases of the elderly. However, it must also be recognized that basic research, the products of which reliably prove exploitable, requires the same long-term approach to funding as the designated socially important areas mentioned above. In conclusion, the existing problems in Europe in the areas of research funding and infrastructures (which have long been the unheard grumblings of scientists at scientific meetings) have been articulated by organizations that represent a large proportion of the European life science community. Science funding policy is a matter for scientists as well as politicians and policy makers. It is heartening that scientists are starting to take more responsibility for changing what they see as wrong with the existing structures. It is to be hoped that the encouraging signs that the European Commission is receptive to the offer of help in drafting the forthcoming Framework Programmes mature into a reality. Equally it is hoped that scientists reading this article will show their willingness to support this important initiative by communicating with the ELSF at http://www.elsf.org, and by engaging their colleagues in discussions on the topics covered in this article. References 1 Chien, S. and Silverstein, C. (1993) Economic impact of applications of monoclonal antibodies to medicine and biology. FASEB J. 7, 1426–1431 2 Köhler, G. and Milstein, C. (1975) Continuous cultures of cells secreting antibody of predefined specificity. Nature 256, 495–497 3 Milstein, C. (1984) From the structure of antibodies to the diversification of the immune response. Biosci. Rep. 4, 275–297 4 Silverstein, C. et al. (1995) A few basic economic facts about research in the medical and related life sciences. FASEB J. 9, 833–840 5 Second European report on scientific and technological indicators (1977) Published by, and available on request from, the European Commission. 6 Communication from the Commission to the Council, the European Parliament, the Economic and Social Committee and the Committee of the Regions: Towards a European research area (2000) Published by the European Commission, and available via the CORDIS comdocument library (http://dbs.cordis.lu/EN_COMDI_ search.html); document reference COM(00)6.
Cancer classification with DNA microarrays
References 1 Wang, D.G. et al. (1998) Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 280, 1077–1082 2 Roberts-Thomson, I.C. et al. (1996) Diet, acetylator phenotype, and risk of colorectal neoplasia. Lancet 347, 1372–1374 3 Kristensen, V.N. et al. (2000) Genetic variants of CYP19
(aromatase) and breast cancer risk. Oncogene 19, 1329–1333 4 Hilgers, W. and Kern, S.E. (1999) Molecular genetic basis of pancreatic adenocarcinoma. Genes Chrom. Cancer 26, 1–12 5 Golub, T.R. et al. (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286, 531–537 6 Galili, N. et al. (1993) Fusion of a fork head domain gene to
Outlook
PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat. Genet. 5, 230–235 7 Alizadeh, A.A. et al. (2000) Distinct types of diffuse large Bcell lymphoma identified by gene expression profiling. Nature 403, 503–511 8 Ross, D.T. et al. (2000) Systematic variation in gene expression patterns in human cancer cell lines. Nat. Genet. 24, 227–235
Science funding and infrastructures in Europe European science in crisis. Scared? Then read on; you should be. I argue that we cannot sit back for much longer and watch our best scientists emigrate to the USA for the most productive part of their career, and that European scientists should not tolerate a funding system that neither rewards an investigator’s brilliance nor the innovative nature of their research. The EC Framework Programme is due for a face lift: scientists should wield the scalpel this time. he year 2000, Europe, the cradle of modern science, the dawning of a new scientific era, and a time to reflect on 400 years of excellence in fields as diverse as mathematics and biology. And what of the future? Well, for many it lies in the USA, because European science, one of our most important domestic products, is still funded and organized piecemeal and unreliably by national research councils, foundations, industry and the European Community (EC). This is particularly true in the life sciences, and is largely owing to the fact that the product of basic research is knowledge, a commodity at once intellectually invaluable and economically valueless without an application. Herein lies the dilemma for policy makers who manage public money. European policy makers have increasingly turned their back on free thought and creative brilliance, and concentrated more on a demand- and applicability-driven scientific culture. Although targeted research is, without doubt, necessary to tackle pressing social demands, basic research, driven primarily by a hunger for knowledge, has given rise to products of spectacular usefulness and completely new fields of research. The value of pure research has long been recognized in the USA, where the wisdom of massive federal investment in basic science is taken for granted. Recent history abounds with examples of socio-economically exploitable discoveries arising from basic research, and who better to promote this idea than scientists? Scientists in the USA do, after all. Indeed, organizations such as the Federation of American Societies for Experimental Biology (FASEB) carry out periodic research into the socio-economical payoffs of investment in basic research. In special features and policy forum articles we are treated to highly persuasive arguments that are supported by numerous examples. For instance, an analysis of the economic impact of monoclonal antibodies1 describes the origin of their development from the fundamental research of immunologists in the 1970s, who wished to understand how the immune system could produce such a large number of different antibodies. This led Köhler and Milstein2,3 to address the problem by developing immortalized cell lines that produced homogenous antibodies to a given antigen
T
0168-9525/00/$ – see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0168-9525(00)02067-9
(myeloma–lymphocyte hybrids). Today, after many years of research and development in different directions, monoclonal antibodies are an invaluable tool in the diagnosis and treatment of disease, not to mention many other non-medical applications. It must be stressed that other basic research in the fields of immunology, oncology, genetics and animal cell culture greatly facilitated the development of monoclonal antibodies. This synergy created by ‘cross-fertilization’ of ideas between different fields of basic research is a fundamental characteristic of the culture of free thinking generated in an unfettered research environment. Further examples of the value of basic research are numerous. The discovery of genetic recombination and the organization of the genetic material of bacteria by Joshua Lederberg opened the way to the production of recombinant proteins, a development of incalculable value. More recently, the study of viral genetics and replication has spawned numerous start-up companies that are concentrating on identifying novel nucleotide analogues as viral reverse transcriptase inhibitors, or peptide-like molecules as viral protease inhibitors. Indeed, the field of molecular biology itself, and its subsequent commercialization in biotechnology, was born out of basic research, the primary aim of which was to increase knowledge. In addition to the economic worth of basic research, the savings to the health system and society in general resulting from the exploitation of basic research discoveries are considerable 4. These range from vaccines and infectious disease treatment to prevention of dental disease. It is, perhaps, because so many advances in healthcare are taken for granted, that their origins in basic research, a practice that has largely remained impenetrable to much of the public, are overlooked. The socio-economic value of basic research is impressively stated in ‘America’s Basic Research; Prosperity Through Discovery’ (http://www.ced.org/pubs/basicresearch.htm), published in 1998 by the Committee for Economic Development (CED). It concludes that basic research in science and engineering, funded predominantly by the federal government, has made a major contribution to the TIG August 2000, volume 16, No. 8
Andrew Moore moore@ embl-heidelberg.de EMBO (European Molecular Biology Organization), Postfach 1022.40, D-69012 Heidelberg, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. 329
Outlook
COMMENT
growth of the US economy (12–25% since the second world war), sowing the seeds for private investment in the exploitation of its results. Furthermore, it recognizes that funding should be allocated purely on merit, regardless of potential applicability of a given area of research. It is no coincidence that the following words were used on the other side of the Atlantic: ‘There is only one proved way of assisting the advancement of pure science – that of picking men of genius, backing them heavily, and leaving them to direct themselves’ [James B. Conant (1893–1978), American chemist, diplomat and educator]. It has long been recognized that this attractive research culture in the USA lures many excellent European minds to the USA, sometimes for ever, and at least for the period in their lives when they are most productive. The relative unattractiveness of Europe is exemplified by the fact that there are twice as many degree-level European students in the USA as American degree-level students in Europe5. Europe’s predicament is further elaborated in a recent document from the European Commission6, which begins with the following statistics: ‘The average research effort in the EC is currently 1.8% of Europe’s GDP, as against 2.8% in the US and 2.9% in Japan’: the trend is towards a greater gap. Furthermore, in the US and Japan, the number of researchers as a proportion of the industrial workforce is more than double that in Europe. These facts have contributed to a trade deficit in hi-tech products of EUR 20 billion per year over the past ten years, a figure that appears to be increasing. However, the established EC funding ethos persists, and by over-concentrating on asking what the needs of society are, is liable to: • over-fund demand-led, short-term science, hence damaging basic research and restricting the pool of ideas from which applications can spring • exclude niche areas which are important to smaller companies • convert the research programme into an instrument for commercial research, which is best funded and performed in a commercial rather than academic context • possibly raise unreasonable hopes for society. For example, society asks for a cure for cancer, but the way towards that is obviously a tortuous and complicated pathway. It is not reasonable to expect to achieve such a goal within the three years of the Programme. The success of science policy in the USA is partly due to political lobbying by scientists. This is accepted as a rightful activity; almost a professional duty. In addition the Internet abounds with US documents analysing the cost:benefit ratio of investment in basic research. A surf through the equivalent European Internet literature leaves one stranded miles from the beach, with no new wave in sight; a new wave is what is needed in Europe, and only scientists can start it. At a meeting last September, scientists from different countries, and European organizations met in Heidelberg under the auspices of the European Molecular Biology Organization (EMBO), and with the support of the Federation of European Biochemical Societies (FEBS), the European Molecular Biology Laboratory (EMBL) and the European Life Scientist Organization (ELSO), to establish the European Life Sciences Forum (ELSF; http://www.elsf.org). The ELSF proposes to advise the EC in the drafting of the sixth (and subsequent) Framework Programme, drawing on the expertise and experience of practising scientists. First among its aims is to convince the EC of the socio-economic 330
TIG August 2000, volume 16, No. 8
Science funding in Europe
value of strong and consistent funding of basic research. This must be accompanied by a more panEuropean approach to research infrastructures and funding in which young investigators receive specific support in establishing research groups and are part of a network. European scientists must follow the example of their American peers and, although it might be considered a dirty word by the more-reserved Europeans, lobby the EC. The advice that the ELSF seeks to offer is the advice of active scientists, who know best how to advance towards scientific or technical goals. They must advise policy makers in the EC (who have the complex, and often underestimated, task of balancing many priorities) where and how to invest their money in order to receive a greater return. European scientists have, in general, abdicated their responsibility, and deprived policy makers of a vital source of advice and information. It is not a simple matter to look into the future and try to predict the socioeconomic outcomes of basic research without the confidence of reliable factual information; but it need not be a matter of blind faith. The ‘short-termism’ generated by the constantly changing criteria for eligibility for a Framework Programme grant makes some areas of research extremely difficult to pursue with continuity and an adequate workforce. This is not to say that applied or socio-economically important research should be replaced by or neglected in favour of research that is less application-driven. It is clearly necessary and desirable to demarcate areas of need, such as cancer, cardiovascular disease and diseases of the elderly. However, it must also be recognized that basic research, the products of which reliably prove exploitable, requires the same long-term approach to funding as the designated socially important areas mentioned above. In conclusion, the existing problems in Europe in the areas of research funding and infrastructures (which have long been the unheard grumblings of scientists at scientific meetings) have been articulated by organizations that represent a large proportion of the European life science community. Science funding policy is a matter for scientists as well as politicians and policy makers. It is heartening that scientists are starting to take more responsibility for changing what they see as wrong with the existing structures. It is to be hoped that the encouraging signs that the European Commission is receptive to the offer of help in drafting the forthcoming Framework Programmes mature into a reality. Equally it is hoped that scientists reading this article will show their willingness to support this important initiative by communicating with the ELSF at http://www.elsf.org, and by engaging their colleagues in discussions on the topics covered in this article. References 1 Chien, S. and Silverstein, C. (1993) Economic impact of applications of monoclonal antibodies to medicine and biology. FASEB J. 7, 1426–1431 2 Köhler, G. and Milstein, C. (1975) Continuous cultures of cells secreting antibody of predefined specificity. Nature 256, 495–497 3 Milstein, C. (1984) From the structure of antibodies to the diversification of the immune response. Biosci. Rep. 4, 275–297 4 Silverstein, C. et al. (1995) A few basic economic facts about research in the medical and related life sciences. FASEB J. 9, 833–840 5 Second European report on scientific and technological indicators (1977) Published by, and available on request from, the European Commission. 6 Communication from the Commission to the Council, the European Parliament, the Economic and Social Committee and the Committee of the Regions: Towards a European research area (2000) Published by the European Commission, and available via the CORDIS comdocument library (http://dbs.cordis.lu/EN_COMDI_ search.html); document reference COM(00)6.