Genopole®, a ten year race to competitiveness

Over the past ten years, Genopole®, with its focus on genomic and genetic research, has been instrumental in putting France on the global biotechnology map. Bringing academic research together with innovative businesses, this outstanding biopark has set its sights first and foremost on developing the therapeutic treatments of the future.

Established in 1998, Genopole®, the first French biopark dedicated to research in genetics, genomics, post-genomics and biotechnology, now has 21 public and private laboratories in Evry dedicated to academic research, under the supervision of the CNRS, CEA , INSERM and INRA, as well as 63 biotechnology companies and university courses, totalling some 2,000 jobs. Together, they have one ambition: innovation in therapeutic treatments.

It all started with the AFM (French Association against Muscular Dystrophy). Noting that the limited profit potential in developing medication for some seven thousand known genetic diseases meant that pharmaceutical companies were not investing in the necessary research, the association was convinced that the only possible answer was gene therapy. For this, the necessary first step was to map the human genome. The demands of this enormous project allowed them to mobilise the finances generated by the Telethon to create Généthon, an ultramodern laboratory established in Evry twenty years ago. The laboratory is headed by biologist Jean Weissenbach, and is supported by Nobel laureate Jean Dausset’s Centre for the Study of Human Polymorphism, headed by Daniel Cohen.

The success has been so significant (publication in 1992 of the first physical maps of the human genome and in 1993 of the first genetic and physical map of the entire human genome) that the government of France picked up the baton. The government created both Genescope, the national gene-sequencing centre and the international coordinator of the international Human Genome project, completed in 2003, and the National Centre for Genotyping, which tracks genes implicated in the genetic predisposition to common hereditary diseases. Genopole® Evry/Ile de France was born, soon followed by younger siblings in Lille, Marseille, Montpellier, Rhone-Alpes, Strasbourg, Toulouse Midi-Pyrenees and West, which together make up the national Genopole® network.

Genopole®’s budget over the past five years (2002 - 2006) has totalled € 70.62 million, of which the largest share (64%) was provided by local government, 40% by the Ile de France regional council and 24% by the General Council of the Essonne. In addition to the GIP’s own funds, Genopole® received support from the CCIE (the Chamber of Commerce and Industry of the Essonne), the AFM, local authorities providing support for other activities on the Genopole® campus (such as the conference centre, the plant nursery, etc.), and French government and EPST support allocated to laboratories and national research centres (salaries, operations, investment).

The goal is twofold: to accelerate the industrialization and automation of research by creating multidisciplinary teams of biologists, mathematicians and engineers; and, by bringing researchers and industrialists together on the same site, working in a cluster mode, to advance the development of biotechnology. This is a major undertaking, as the scope of the work is extremely broad: not only DNA, but all methods and techniques that use living materials, including organisms, cells, subcellular and molecular components.

And there is no lack of international competition in this field, not least because biotechnology is expected to play a key role in a highly coveted field: medicine. "We estimate that in 2010, 80% of medicines will be derived from biotechnology. Biologists have gradually overtaken chemists in the pharmaceutical industry," emphasises Pierre Tambourin, CEO of Genopole®. In addition, biotechnology will be the tool of choice not only to identify the genes responsible for genetic diseases, but also for the majority of human pathologies with a genetic basis, such as obesity, cancer, cardiovascular disease, diabetes and asthma - a screening process which will in turn lead to the development of new drugs. "We will move from generalised medicine to personalised medicine, where genetic data will become more and more relevant," asserts Pierre Tambourin. Finally, biotechnology has a promising future in the fields of the environment, agriculture, industrial chemicals, materials such as bioplastics, and so on. All of which is producing a fierce international race towards competitiveness.

01.Reinforcing the appeal of a competitive cluster

Although we think of biotechnology today as a major new scientific and economic issue, biotechnology already has some 10,000 years of history, dating from the time humans first became sedentary, developed agriculture and began to select plants, domesticate certain animals, produce bread, cheese and alcoholic beverages using, unbeknownst to them, micro-organisms. Today the applications of biotechnology cover a vast field. In this area, the United States has taken the lead not only over France but over Europe as a whole. In the late sixties, the Americans launched a comprehensive national program with the goal of overcoming cancer in fifteen years. An admittedly unreachable goal, but one which has enabled them to create a powerful tool for scientific research through the National Institutes of Health (the NIH), under which even the development of molecular biology is growing rapidly. We are now witnessing the creation of the first biotechnology businesses created directly as a result of this often extremely fundamental research.

In France, however, are there many obstacles that hinder growth. One is the supremacy of the “hard” sciences - mathematics and physics - over the “soft” sciences, including the life sciences. In addition, the fragmentation of the public organisations on which the life sciences depend and the competition under which they operate does not favour the coordination of their efforts. Moreover, French researchers are reluctant to turn to industry for support, believing that this would be an unnatural alliance and one which would threaten the path of fundamental research. Finally, the culture of innovation is not part of the education of future academic researchers. Genopole® marks a real break with all of these traditions. “This is, in effect, a triple revolution, continues Pierre Tambourin. Scientific first and foremost, as we move towards biology on a large scale, using new technologies (robots, computers, etc.); industrial, with the growing awareness of the importance of biotechnology; and finally cultural, through the phenomenon of the cluster and the creation of innovative businesses.” It is Evry, about thirty miles from Paris and the location of Généthon, which plays host to this adventure. And it is conducted in close collaboration with the young university of Evry-Val d'Essonne, which as yet does not even offer a degree in biology.

If convincing researchers, both French and foreign, to move to the site appears to be a challenge, it seems even more improbable that these researchers can be convinced to file patents to create innovative companies able to conquer new markets. Yet, the newness of this greenfield site is in fact more of an asset than a liability in this pioneering endeavour, particularly as local authorities, delighted to see the development of a pool of jobs, are taking active steps to assist them. In addition, the pooling of resources and scientific equipment - including ten technology platforms (making both advanced equipment and expertise available to researchers) including three which have been designated national level resources* for their high levels of expertise, four technical platforms (with open access to the equipment), and a dedicated building stock of some 90,000 m2 - are magnets to attract skills, as is Genopole’s® own visibility and reputation, representing as it does a quarter of all French biotechnology facilities (half of those in the Paris region). In this high-risk sector, the biopark has been involved in the creation of some 65 enterprises or start-ups, and has contributed to a more than a hundred projects. Above all, these companies have raised some 180 million euros with an initial disbursement to Genopole® of 30 million euros. Twenty-two new drugs are currently under development and the first wave is expected to reach the market within two years. Already, the company Novagali, specializing in ophthalmic products, expects to commercialise its first product for the treatment of dry eye (a syndrome linked to the degradation of the tear membrane responsible for dry spots on the cornea, causing itching and burning).

Success is still fragile, however, despite the progress to date. For, although France has seen the creation of many businesses during the past decade, they remain small companies with limited capital: “In comparison, only twelve companies are currently listed on the French stock exchange, compared to more than fifty in the UK alone.” As for bringing about a shift in attitude, “learning to work collectively takes time,” acknowledges Pierre Tambourin. Similarly, while the government is aware of the strategic importance of the issue, funding is still lower than that available in, for example, Munich, Barcelona or Singapore. "Granted, Genopole® has been endowed with more than 120 million euros since its inception, but public investment in Singapore is ten times higher." This level of investment generates a sure attraction for skilled workers with which it is difficult to compete. French hesitancy with respect to this field may be due to the public’s admittedly legitimate mistrust of the life sciences in the wake of the scandals around tainted blood, growth hormones and mad cow disease.

* This refers to the production platforms for DNA chips and plant DNA chips and to the DNA and cell bank. For more information, visit the CEA.

02.The multidisciplinary advantage

While matching the performance of the cutting-edge campuses at Cambridge in the United Kingdom or San Diego in the USA appears difficult to achieve, Genopole® intends make a permanent mark for itself on the global biotechnology landscape. A challenge that requires Genopole® to remain at the forefront of scientific developments - especially synthetic biology, now poised to revolutionize the field of biology. A particularly important line of development has arisen with the recent arrival on the site of I-Stem, a laboratory specialising in stem cell research, endorsed by INSERM and supported by the AFM. “Therapeutic in design, this project is working to develop solutions for human pathologies with no real treatments today,” says Pierre Tambourin. But if the future of medicine, according to the researcher, is “man regenerated by his own cells”, it is ever-more important that, in the first country in the world to create a national ethics committee, freedom of research is not held back. But stem cell research remains a highly sensitive topic in France and one that raises many concerns. “The ethical issues are real, but the principle of precaution should not be used as a pretext for making a principle of inaction,” he warns. Thus, according to some, the research ban on therapeutic cloning is an impediment to research on cells that might one day be used to create “spare-part organs”. Hence the urgent need to educate society about these issues, and for Genopole® to assert its teaching vocation to accompany the debate, in collaboration with the humanities and social sciences, as the law on bioethics comes up for revision in 2009.

To further stimulate high-level medical research, the campus is also gambling on a fertile dialogue between teachers, researchers, entrepreneurs, and, soon, doctors as well. This is, in any case, the future anticipated as a result of the construction of a nearby hospital in the southern Paris region of Evry/Corbeil-Essonnes, scheduled to open in 2011, and the construction of the Centre for Clinical and Translational Research on the same site. The latter aims to promote continuity between basic, clinical/technological and pre-industrial research. The intent is to bring together, and to aid in the collaboration of, specialists working at all stages of the process - from the laboratory to the bedside - ensuring that information flows in both directions. “We believe that this will be a considerable asset,” says Pierre Tambourin.

And while Genopole® can already boast of being the premier French bio-industrial production cluster, it now aims to reach the premier rank in Europe. The opening in October 2008 of the Centre for bio-production of therapeutic molecules should help achieve this ambition, and contribute to fulfilling the Cancer Plan, as more than 30% of anticancer drugs in development are molecules of biological origin. Thus, new companies in this highly strategic sector are preparing to join the cluster in the coming years. From the production of biomolecular drugs, new enzymes, therapeutic vectors for gene therapy in the treatment of rare diseases, to the use of new metabolic pathways outlined by the National centre for gene sequencing, the director believes in the power of multidisciplinary teamwork to face up to the global competition in biotechnology. “This is a circumstance in which we will benefit from French expertise in math, physics, chemistry ... a multidisciplinary approach which is becoming increasingly necessary if we are to address the extraordinary complexity of life.

03.Reinforcing the appeal of a competitive cluster

If Genopole® has played a pioneering role in combining skills in the field of genetics, it has also participated in the design and implementation of the global competitive cluster Medicen Paris Region. In 2005, as part of a new industrial policy designed to stimulate innovation in France, the government decided to create competitive clusters following the American model, typified by Silicon Valley in California. The goal? To encourage, in a given territory, the synergies between research units, training centres and businesses, endowed from the outset with 1.5 billion euros of public funding (from 2006 to 2008), tax exemptions and a reduction in payroll taxes. In short, the government is adopting an approach similar to that advocated by Genopole®, “so that France may take the necessary steps to develop a cluster-friendly culture,” says Pierre Tambourin, who was the project manager of the Medicen competitive cluster and subsequently its vice president. “The goal is to provide a response to interrelated issues,” he adds. With competitive clusters, the French government intends to promote the creation of myriad innovative businesses, the champions of tomorrow, in the context of globalization. It is a way both to pool talents and resources, and to create the economic conditions which can help France to avoid a brain drain.

Neuroscience, oncology (cancer studies), the study of infection, molecular medicine, biomedical imaging: Medicen Paris Region, funded equally by the State and by local governments (44 million euros over nearly three years) has the task of ensuring that all the players in health and medicine in the Ile-de-France region work together. “This is about tackling the challenges of public health at a time when the population is aging and more and more people are concerned,” says Michel Vieillefosse, the director general. With this in mind, the centre is endorsing certain projects to enhance their credibility and visibility, such as the Institute of Vision, which is opening its doors at the Quinze-Vingt medical centre. For Genopole®, an active member of the centre, it is an ideal moment to become involved in the fruitful collaborations which exist in Ile-de-France. In the field of molecular and cellular medicine, in 2006 Medicen Paris Region endorsed the IngeCELL project, in which Généthon, I-Stem and a number of Genopole® businesses are involved. Its mission: to produce a range of human cells specific to an organ or tissue in order to develop a business in industrial pharmacology that meets both the needs of the current market (pharmaceutical screening, toxicological studies), and future markets such as cell therapy.

In its role as a competitive cluster, Genopole® - which expects to have some 4,000 people working on its campus in 2010 - hopes to become increasingly well-known and attractive to skilled workers. Particularly since Medicen, which counts among its members the Institut Pasteur, CNRS, INSERM and eight universities, aspires to nothing less than becoming, within the next four or five years, the premier European industrial cluster in therapeutic innovation as well as one of the world leaders in the field - provided, once again, that they are able overcome the cultural resistance that hinders the development of collaborative projects. “The potential exists, insists Michel Vieillefosse. The Île-de-France region accounts for half of French medical research and approximately 10,000 researchers. This region also hosts 8 pharmaceutical companies with global reach and includes our partners Sanofi-Aventis, Servier and Ipsen, 800 small and medium-sized enterprises in the life sciences and 40,000 hospital beds - a tremendous opportunity for clinical trials. What other region in Europe has these advantages?

Today, France has 71 competitive clusters across all sectors, including 7 that are world-class and 8 which expect to become so in the future. They are supported by both the left and right of the political spectrum, united by a broad political consensus. Yet in a recent book, Les Pôles de compétitivité. Que peut-on en attendre ? *, respected economists believe that these centres are not necessarily a panacea. They point out, for example, that state intervention favours established players, not small- and medium-sized enterprises, which are those that have made the fortunes of Silicon Valley in the United States. Regarding Medicen, it is nevertheless still too early to take stock. Status-check in five years time?

* Les Pôles de compétitivité. Que peut-on en attendre ? (Competitive Clusters - What Can We Expect?). Published by Rue d'Ulm, part of a series of the Cepremap (CEntre Pour la Recherche EconoMique et ses APplications / Center for economic research and its applications), by Gilles Duranton, Philippe Martin, Thierry Mayneris and Florian Mayer.

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