February 2017
Summary
Réalités industrielles
Industrial biology: the technological, economic and societal issues of biotechnology
Complete issue
This issue was coordinated
by Françoise ROURE
This issue was coordinated
Editorial
By Carlos MOEDAS
Commissaire européen Recherche et développement
Avant-propos
By Jean-Luc PUJOL
Haut Conseil des biotechnologies (HCB)
et Françoise ROURE
Conseil général de l’économie (CGE)
The scientific, technical and innovative potentials
The knowledge necessary for industrial biology
By Pierre MONSAN
Président de la Fédération française de biotechnologie et président fondateur de Toulouse White Biotechnology
Industrial biology has arisen out of the convergence between the life and engineering sciences. It has come out of the extraordinary advances made in scientific knowledge and the new tools now available: the falling cost of genome sequencing (and, to a lesser extent, gene synthesis), the increase in computing power, the capacity for making simulations, improved methods and tools (both biological and analytic), etc. Out of this combination of advances has emerged synthetic biology, i.e., the possibility of rationally rearranging a microorganism’s genome in order to create original metabolic channels by introducing enzymatic activities (not previously described in research studies) and systems of regulation. This industry has chalked up successes, among them: hydrocortisone, artemisinic acid, 1,3-Propanediol and succinic acid.
Big data in oncology: From basic research to applications in behalf of patients
By Emmanuel BARILLOT
Directeur de l’unité INSERM 900 à l’Institut Curie
et Philippe HUPÉ
Directeur adjoint de la plateforme de bioinformatique de l’Institut Curie
In research and care, oncology is now tightly linked to digital technology, mainly owing to the means used to explore cells at the molecular level through genome sequencing. The mutations thus brought to light are potential targets for a therapy based on inhibitors, the new pharmaceutical products full of promise for the personalization of treatments. National plans are being made for “precision medicine”. This calls for sequencing hundreds of thousands, or even millions, of human genomes in the coming years with, as a consequence, the production of data in petabytes. In the countries advanced in this domain, an industry will emerge that interests start-ups and big players in the digital economy.
Advanced metrology’s contribution to the assessment of medical-biological tests and the improvement of their reliability
By Vincent DELATOUR
Expert Biomédical/Biomarqueurs au Laboratoire national de métrologie et d’essais (LNE)
The reliability of laboratory tests is a major public health issue, since medical-biological tests are used to make trustworthy diagnoses and adjust treatments. The science of measurement is fundamental to assessing and improving the comparability and accuracy of tests. For one thing, the metrological connections made between the results of a test and its reference methods – obligatory under the 1998 EU directive (98/79/CE) on in vitro diagnostic medical devices – enable us to harmonize findings from various laboratories of medical biology, even when they have used different dosage methods. For another, the reference methods for determining the target values of quality control samples can serve to verify the precision of the doses used by these laboratories, under condition that the control samples are commutable, i.e., they imitate the behavior of samples from patients.
Standardizing engineering techniques in biomedical research: Centers of biological resources
By Bruno CLÉMENT
Directeur de l’unité Inserm Nutrition, métabolismes et cancer à Rennes et directeur scientifique de l’Infrastructure nationale BIOBANQUES
Paul HOFMAN
Professeur de pathologie au CHU de Nice Mireille DESILLE Ingénieure de Recherche au CRB-Santé du CHU de Rennes
et Georges DAGHER
Directeur de recherche à l’Inserm et coordinateur de l’Infrastructure nationale BIOBANQUES
High-speed technology has deeply changed research in the life and health sciences. This research has considerable spin-offs for understanding illnesses and providing care. The mainstay of this progress has been access, in compliance with ethics and the law, to biological samples of a guaranteed quality and traceability. In France, “centers of biological resources” collect, stock, safeguard and distribute samples with the relevant clinical and biological data. This infrastructure is evolving toward “biobanks”. No longer simply warehouses with biological samples, this new generation of institutions is a full-fledged partner in therapy and research. Given the power of high-speed techniques (capable of generating masses of data from a single sample) and the advent of “precision medicine” (based on analyzing these masses of data), it is necessary to quickly implement preanalytic standards and organize a multidisciplinary meeting of experts.
The contribution of bioengineering to innovative applications: Materials of biological origin
By François TÉNÉGAL
Directeur général d’IFMAS (Institut Français des Matériaux Agro-Sourcés)
et Patricia KRAWCZAK
Professeur de l’Institut Mines-Télécom à Mines Douai, Secrétaire général du Comité d’orientation stratégique d’IFMAS
Founded in 2012, IFMAS (Institut Français des Matériaux Agro-Sourcés) is a private R&D firm with expertise in the chemistry of plant life and materials of biological origin. Its vocation is to carry out R&D programs oriented toward applications and performance indicators for biomaterials. Beyond their environmental benefits, the findings from these programs must also contribute to major technological innovations by developing biomaterials with new qualities in comparison with what is currently found on the market.
New plant-breeding techniques: A few words from the world’s fourth seed company (Limagrain) on innovation in agriculture
By Jean-Christophe GOUACHE
Directeur des Affaires internationales de Limagrain
Limagrain, an international agricultural cooperative, ranks as the world’s fourth seed company. It backs innovations in farming, in particular new plant breeding techniques. These key vectors of progress in genetics will help agriculture come to grips with many an issue. These new tools, which supplement the historical techniques for plant-breeding, are more efficient and can produce genetic diversity. If they are to be used on a large number of plant species and by all seed companies in Europe (thus maintaining and diversifying players in this field), regulatory restrictions and costs must be acceptable in view of the target market’s size. Limagrain defends a regulatory approach that is proportional to the risks, foreseeable, transparent and scientific. Such an approach is the necessary condition for: avoiding restrictions on innovations (without justifiable grounds), keeping these new techniques from being stigmatized and boosting public confidence in agricultural products. From this perspective, Limagrain supports the proposal that, made by five trade organizations, would place certain plant-breeding techniques outside the scope of the EU directive (2001/18/CE) on genetically modified organisms.
Personalized medicine: How far? A research challenge for the pharmaceutical industry and its partners
By Marc BONNEFOI
Vice-président R&D de Sanofi France
Procedures no longer adapted to modern health systems are impediments to the traditional R&D studies conducted by the pharmaceutical industry. The process of identifying a target, developing a drug that acts on it and testing the drug in one or more pathologies is long, onerous and uncertain. In contrast, “translational research” opens the way toward a “precision medicine” focused on the patient and the processes involved in his/her illness condition with the goal of designing a specific, targeted treatment. This change of paradigms has, over the past few years, moved pharmaceuticals from the era of chemistry into the age of biotechnology. This shift requires scientific excellence and reorganization, a source of open innovations. The cooperation between big laboratories, academic research facilities, health-care centers and biotechnological companies will boost the trend toward an increasingly personalized form of care. The medicine of the future will take into account factors not just medical but also behavioral, environmental, ethical, etc.; and will rely on big data. It requires reorganizing payment methods in the current system of care and adapting rules and regulations. Bearing opportunities, this personalized medicine is a response to the imperative of socioeconomic and sanitary growth in developed countries, an imperative entailing strong management and appropriate forms of governance.
Hydrocarbons produced by industrial biology: Global Bioenergies’ background and prospects
By Marc DELCOURT
Directeur général de Global Bioenergies
et Ronan ROCLE
Chargé d’affaires
Global Bioenergies was founded in 2008 on a breakthrough in industrial biology: the production of hydrocarbon gases through fermentation. The company has focused on the biological production of isobutane, a major elementary brick in organic chemistry that can be converted into fuel, plastic, organic glass or elastomer. Global Bioenergies is still making its process more efficient, nowadays by conducting tests on its demonstration plant in Germany and making plans for launching full-scale operations in factories.
Modeling biological systems: A way to produce several forms of innovation
By François IRIS
Directeur scientifique, fondateur et président de BMSystems
et Manuel GEA
Directeur général, vice-président R&D Systèmes d’Information et co-fondateur de BMSystems
Given a failure rate of more than 90% during clinical phases of testing, the current system for discovering new drugs is no longer tenable. Contrary to the “dominant mind-set”, the problem is not of a technological sort; nor does it have to do with processing big data. The problem is our poor understanding of processes in living beings and of the way certain concepts (on which R&D programs are based) of complex illnesses have been worked out. Readers will become aware of the life processes at work at the very point where the distinction between complex and complicated systems becomes crucial. They will thus realize the necessity of taking into account the warnings issued by Stanford University, which, in 2014, set up the Meta-Research Innovation Center (METRICS) for the purpose of improving data quality and publications. Through the example of the successful response to a major public-health risk – the multiresistance of bacteria to antibiotics – an approach to building a nonmathematical heuristic model is described that made it possible to turn viral phage therapy into an innovative diagnostic/therapeutic biocontrol solution that uses bacteriophages produced though three patented technologies stemming from this model-building.
The economic surge
Understanding value chains in industrial biotechnology
By Jim PHILP
Conseiller Biotechnologies à DSTI/OCDE
Alain SCHIEB
Président de BACKCASTING SAS et consultant auprès de l’OCDE
et Mohamed Majdi CHELLY
Ingénieur d’études à ENGIE Cofely France
Actual and future value chains regarding the industrial bioeconomy show that OECD countries will continue until 2050, at least, to be net importers of fossil fuels and also of biomass. In order to see a flourishing industrial bioeconomy in Europe, there is a need for competitive sources of biomass, including agricultural and forestry residues and waste materials. In principle, it should be easy to substitute local production in Europe to imports, given the size of demand. However, relative prices of fossil fuels versus renewable biomass will be a key to the growth of bio-sourced products in the European market. At present the competition is unwinnable: the fossil industries have a century of a head start and they still receive enormous subsidies. Creating a level playing field should be a pre-requisite for Europe. From a public policy perspective, creating a level playing field is both a high priority and a legitimate goal since it does not imply any selection by a government of a given technology pathway. The “technology neutral” requirement for public policies would be met while enforcing a level playing field that would still open the door for new entrants and particularly a circular and industrial bioeconomy.
Industrial bioeconomics at the regional level: The biorefinery at Bazancourt-Pomacle, a springboard for a territorial strategy
By Maryline THÉNOT
Professeur, responsable du département Finance, chaire de « Bioéconomie industrielle » de NEOMA Business School
et Honorine KATIR
Ingénieure de recherche, chaire de « Bioéconomie industrielle » de NEOMA Business School
Its international dimension makes the biorefinery at Bazancourt-Pomacle, an agribusiness complex located near Reims (Marne Department, France), stand out. This pioneer in bioeconomics is expanding as part of a regional development program. On the same location, an industrial pole is associated with a pole of open innovation; and regional farming cooperatives are heavily involved in this complex. This unique ecosystem is described, as well as its “metabolism” and strong potential for stimulating local growth at a time when bigger administrative regions are being formed in France.
Intellectual property and the maturity of innovations in industrial biology
By Nathalie MANTRAND-FOUSSADIER
Consultante senior en chimie, chimie verte et biotechnologie blanche, Questel Consulting
Having developed strongly over the past ten years, synthetic biology has seen new technologies and players emerge. A study of the patents filed in this field helps us interpret these developments and the positioning of players in this market. A glimpse of current trends in synthetic biology, in particular the applications in chemistry and energy…
The map of industrial biology in France: Medical biotechnology
By Gaëtan PONCELIN DE RAUCOURT
Ingénieur en chef des mines, chef du bureau des Industries de santé à la direction générale des Entreprises – ministère de l’Économie et des Finances
France was a pioneer in industrial biology owing to Louis Pasteur’s work during the 19th century. This contrasts with the country’s current situation in medical biotechnology. Alongside a few major international leaders on certain market segments (such as Sanofi, Sanofi-Pasteur or bioMerieux) and public research institutes on the cutting edge of international competition (in particular, the CEA, CNRS or INSERM), a vast ecosystem of small, often hyperspecialized, companies has taken shape with backing from public and private pump-priming programs. However most of these firms are toiling to turn top-notch research into an economic success. The arrival of biosimilar medical products on the market and the promises of cellular and gene therapy provide opportunities to French players, who hope to reinforce their positions in world competition.
The value of education and an education in values: Industrial biotechnology
By Vanessa PROUX
École Sup’Biotech, directrice générale, Pôle de compétitivité Medicen Paris Région, présidente de la Commission Formation
et Fabien MILANOVIC
Docteur en sociologie de l’Université René Descartes et enseignant-chercheur à Sup’Biotech
The population of the human species has undergone unprecedented growth: the number of human beings on the planet passing from 1.66 to 6 billion during the 20th century. And the economic stakes in industrial biology have never been so important. The impact will initially be felt in health, agribusiness and the environment. This sector, even more so than in the past, must educate the managers who will have to assist the world during this period of change. Along with solid scientific and technical achievements, there is the need for the capability to adapt, by taking into account factors related to sustainable development and the ecological transition in a context where humanity’s impact on the planet has never been so heavy. For this reason, it is hard to separate the value of the education to be dispensed to future engineers from an education in ethical values.
Role of Nutritional Therapy in Healthcare Innovation: The Need for Reshaping Regulatory Paradigms
By Manfred RUTHSATZ,
PhD Nestlé Health Science, Global Head of Regulatory Advocacy
Over the next decades, the world will undergo profound changes, with its population approaching ten billion, senior citizens making up one out of five, non-communicable diseases (NCDs) increasingly outnumbering infectious diseases, and healthcare costs threatening to reach an ever higher percentage of countries’ GDPs. As daunting as these figures might appear, new scientific insights and technological opportunities coming at an unprecedented pace promise new perspectives and potential solutions to currently unmet needs. ‘Omics’ diagnostics will revolutionize the way we approach prevention, personalize nutrition in healthcare, and how a patient is to be defined. Novel nutrition therapeutic findings will transform disease management, and the microbiome will become a new force in targeting holistic healthcare solutions. This article presents pertinent focus areas to encourage dialogue with regulators, policy makers, healthcare professionals and other stakeholders to revisit current regulatory and policy frameworks at the food-medicine continuum and their respective interpretation, with regards to healthcare.
Including microbiota in corporate strategies for research and innovation: The lessons drawn from MetaGenoPolis, a preindustrial demonstration project
By Joël DORÉ
PhD, directeur de recherche INRA et directeur scientifique de MetaGenoPolis
et David PETITEAU
Responsable du développement de la recherche partenariale sur les projets Microbiome à l’INRA
Beyond the buzz in the media, microbiota should no longer be overlooked by the persons in charge of innovation in agribusiness, nutrition, health or pharmaceutics, nor by the manufacturers and distributors of synbiotics, diagnosticians and people involved in animal health and nutrition. What is meant by the statement, “Yes, boss, we are taking the microbiome into account in our research-innovation strategy”? Although answers differ depending on the field, there are common issues related to this innovative topic. The French National Institute for Agricultural Research (INRA) and, since 2012, MetaGenoPolis (MGP, a preindustrial demonstration project) are playing a leading role in this field. Major questions are moving from the domain of pure science into the realm of applications. A panorama of what is taking shape in each sector concerned in microbiota…
Toward a responsible industrial biology: Ethical and societal questions and controversies
The scope and limits of new plant-breeding techniques
By Nils BRAUN
Responsable scientifique des questions de biosécurité et de biosûreté, Haut Conseil des biotechnologies (Paris)
New plant-breeding techniques have hit the headlines: the CRISPR-Cas9 system is said to signal a revolution in biology. But what is all the hype about? Are these new plants genetically modified organisms (GMOs)? What do regulations have to say? To better understand the issues in current discussions on EU regulations, we must better understand the nature of these new techniques. What are the scope and limits of nucleases? Why are they, since the recent revelations about Cas9’s potential, the center of scientific, economic and societal controversies? Is there a revolution in plant-breeding? The question is not merely technical…
Microorganisms in the soil: Biological tools for reaching the objectives of sustainable development
By Jean-Marc CHÂTAIGNER
Directeur général délégué de l'IRD
et Robin DUPONNOIS
Directeur du Laboratoire des Symbioses tropicales & méditerranéennes
Several farming practices have proven to not be environmentally friendly and demonstrated their limits for achieving food security, one of the clearly set goals on the UN’s Agenda 2030. Given the urgency of finding out how to attenuate climate change and adapt to its effects, innovative approaches are needed to make steep increases in agricultural yields compatible with the conservation of natural resources. Biological tools such as microorganisms in the soil can help reach the goals of sustainable development. Taking the mycorhiza fungus as an example, this analysis presents biotools as a universal solution for attaining these goals.
New biotechniques: Ethical questions and the socioeconomic consequences on agriculture and biodiversity
By Guy KASTLER
Confédération paysanne, membre fondateur du réseau Semences paysannes
Techniques in genetic engineering and informatics have evolved to the tipping point and are now reshaping the part of the process upstream in the production of agricultural goods and services. They have major implications for the legal regulations to be applied to seeds. In the first decade of this century, the cost of genetic sequencing has been divided by 100,000 and the time necessary for it by 2,000, whence a recent spate of megamergers in this field. This reduction in costs is the finishing touch on the process for making farmers dependent, turning them into underlings who follow the digital orders received day after day from the companies supplying equipment, seeds, etc. This trend is going to reduce the biodiversity of cultivated plants, which has been retrenched by 75% during the previous century according to the UN’s Food and Agriculture Organization. Three transnational corporations have placed a lock on the first link in the chain of food production; and no government dares oppose them. Besides farmers’ rights and “food sovereignty”, the political sovereignty of nation-states is menaced.
The misuse and malicious uses of the new biotechnologies
By BrigGen (ret’d) Ioannis (John) GALATAS MD, MA, MC (Army), Manager et CBRN Knowledge Center @ International CBRNE Institute (BE)
MD, MA, MC (Army), Manager, CBRN Knowledge Center @ International CBRNE Institute (BE)
Being one of the sources of independent CBRNE (Chemical, Biological, Radiological, Nuclear and Explosive) expertise, the International CBRNE Institute Belgium (ICI) aims at promoting and developing best practices, standards and innovations in the CBRNE field. The ICI aims to enhance CBRNE risk mitigation at regional, national and international levels. It engages in a wide range of CBRNE-related activities including developing and supporting academic and policy-related research, organizing conferences, seminars and workshops as well as professional development programs for responders. In these activities, the ICI collaborates with other partners such as institutional, academic and corporate bodies and aims to be at the forefront of CBRNE-related activities, from policy to practical application. The Knowledge Centre (KC) is a body within the ICI that aims to provide leadership, best practices, research, support and/or training in the CBRNE area. The pallet of competencies includes technology, business concept, skill sharing or a broad area of study. The KC consists of two parts, namely the CBRN KC and the Explosives KC; both are coordinated by a Steering Committee, responsible for external relations and visibility, while the members of the KCs are pooled in a “Community of Experts” organized in Task Forces (TF). Each KC is represented by a Chairman; Professor Yvan Baudoin for the EKC and Brigadier General (ret’d) John Galatas for the CBRNKC.
Genome-editing: A breakthrough technology
By Hervé CHNEIWEISS
Médecin neurologue, président du Comité d’éthique de l’INSERM
It often happens that scientific discoveries hit the headlines and that the media, eager to attract readers or viewers, announce a new revolution. In fact, such breakthroughs occur very seldom. The discoveries that trigger a change of paradigms do not occur so frequently, since the passage from an academic finding to a technical application is long, arduous and often unsuccessful. Nevertheless, we are now witnessing a technological revolution resulting from control over the genome, recently acquired thanks to the CRISPR-Cas9 and its derivatives.
Miscellany
Additive manufacturing: Where are we?
By Pascal MORAND
Président exécutif de la Fédération de la couture, du prêt-à-porter, des couturiers et des créateurs de mode, membre de l’Académie des Technologies
Joël ROSENBERG
Responsable Innovation à la direction de la Stratégie du ministère de la Défense
et Dominique TURCQ
Président-fondateur de l’Institut Boostzone
A slow, deep revolution is under way via a technological innovation: additive manufacturing will be widely used in the coming years. It will affect not only nearly all industries (know-how, logistics, product design, sales, etc.), but also the global economic system (jobs, supply and demand). Realizing that this vast potential has many consequences and taking note of France’s lag in this field, the Conseil général de l’Armement (CGARM) tried, in 2014, to clarify the situation and formulate recommendations. To this end, it worked with the Chamber of Commerce and Industry in Île-de-France Region (which includes Paris) and Boostzone (a research and training institute) on a report. This report sketched a panorama of the techniques in use, listed their key points, established an international benchmark and presented the manufacturers in control, at the time, of parts of the production chain in 3D-printing. It dwelled on “makers”, start-ups, changing business models and the applications in branches of industry as varied as aeronautics, medicine, the building trade and the fashion industry. The three authors of this report refer to it while updating it with recent developments in this technology, its applications and related public programs.