- Email: [email protected]
Policy to support marine biotechnology-based solutions to global challenges
Forum: Science & Society markets, so will require different policies to achieve the desired returns from marine biotechnology. This is a feature of (i) differences in the relative ratios of public– private contribution to innovation in different fields, (ii) presence of established and competing technologies, and (iii) maturity of the relevant industrial sector, among other factors. Opportunities for international collaboration Marine bioresources are situated in a shared environment, and are rarely constrained by national or geographic borders. The need for effective and equitable access and development of marine organisms motivates consideration of how international cooperation can support sustainable development of marine biotechnology. Such cooperation may enable development of new models for governance of the marine environment – both as related to access and benefit sharing, and also protection of marine bioresources – and enable dissemination of best practices related to molecular aquaculture. Designation of marine protected areas has been useful for preserving habitat and marine organisms, yet the utility of these approaches to marine microbes (often widely dispersed and difficult to enumerate) for instance, or for poorly understood species, is not known. Marine biotechnology, through bioremediation and the development of biosensors to measure changes in environmental conditions including biological and microbial ecosystems, has a role to play here. Yet, in the absence of a sole regulating authority, use of these tools and governance of marine environment is not well coordinated. Rapid progress related to underlying basic research is also providing opportunities for harmonization or initiatives to manage the huge volumes of data that are driving interest in the field.
Trends in Biotechnology March 2013, Vol. 31, No. 3
References 1 Kennedy, J. et al. (2010) Marine metagenomics: new tools for the study and exploitation of marine microbial metabolism. Mar. Drugs 8, 608–628 2 Costanza, R. et al. (1997) The value of the world’s ecosystem services and natural capital. Nature 387, 253–260 3 Oreskes, N. (2004) The scientific consensus on climate change. Science 306, 1686 4 Scannell, J.W. et al. (2012) Diagnosing the decline in pharmaceutical R&D efficiency. Nat. Rev. Drug Discov. 11, 191–200 5 Leal, M.C. et al. (2012) Trends in the discovery of new marine natural products from invertebrates over the last two decades – where and what are we bioprospecting? PLoS ONE 7, e30580 6 Mayer, A.M.S. et al. (2010) The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol. Sci. 31, 255–265 7 Lerman, J.A. et al. (2012) In silico method for modelling metabolism and gene product expression at genome scale. Nat. Commun. 3, 929 8 Markowitz, V.M. et al. (2012) IMG: the integrated microbial genomes database and comparative analysis system. Nucleic Acids Res. 40, D115–D122 9 Arnaud-Haond, S. et al. (2011) Marine biodiversity and gene patents. Science 331, 1521–1522 10 FAO (2012) The state of world fisheries and aquaculture 2012. In World Review of Fisheries and Aquaculture (http://www.fao.org/docrep/016/ i2727e/i2727e01.pdf) 11 Subhadra, B. and Grinson, G. (2011) Algal biorefinery-based industry: an approach to address fuel and food insecurity for a carbon-smart world. J. Sci. Food Agric. 91, 2–13 12 Davidson, W.S. et al. (2010) Sequencing the genome of the Atlantic salmon (Salmo salar). Genome Biol. 11, 403 13 Scott, S.A. et al. (2010) Biodiesel from algae: challenges and prospects. Curr. Opin. Biotechnol. 21, 277–286 14 Wargacki, A.J. et al. (2012) An engineered microbial platform for direct biofuel production from brown macroalgae. Science 335, 308–313 15 The Federal Government of Germany (2012) Biorefineries Roadmap (as part of the German Federal Government action plans for the material and energetic utilisation of renewable raw materials) (www.bmbf.de/ pub/roadmap_biorefineries.pdf)
Disclaimer statement The opinions expressed and arguments employed herein are those of the authors and do not necessarily reflect the official views of the OECD, or of the governments of its member countries.
0167-7799/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tibtech.2013.01.009 Trends in Biotechnology, March 2013, Vol. 31, No. 3
Special Issue: Celebrating 30 years of biotechnology
Unjustified regulation prevents use of GMO technology for public good Ingo Potrykus Emeritus Plant Sciences, Im Stigler 54, CH-4312 Magden, Switzerland
Transgenic plants are regulated for their technology because they have been claimed to lead to uncontrolled and unpredictable alterations of the genome and, therefore, to unpredictable risks to the environment and the consumer. This argument can, however, never justify regulation, because each technology used in plant breeding, so far, has exactly the same consequences. As a result of regulation, genetically modified organism (GMO) product develCorresponding author: Potrykus, I. ([email protected]).
opment is so expensive and time-consuming that it is beyond the capacity of public institutions and for public good. The statement above is one of the lessons from the author’s involvement in the ‘Humanitarian Golden Rice’ project (http://www.goldenrice.org). The research teams of Ingo Potrykus and Peter Beyer worked from 1991 onwards on the problem of vitamin A deficiency in rice-dependent populations. As a solution, they engineered the biosynthetic pathway for provitamin A into rice endosperm. They 131
Forum: Science & Society achieved proof-of-concept in 1999 [1]. ‘Vitamin A rice’ to date is possible only via genetic engineering. To have a practical impact, a scientific result needs to be converted into a product that can be handed out to the needy. Since 2000 the inventors of Vitamin A rice have been working on that task and they have learned many lessons, which, probably, are not familiar to colleagues from academia. A few of those lessons will be presented below. Why do we state ‘unjustified’ GMO regulation? There is broad scientific consensus, which has been published widely by academic and other public institutions, that there is no specific risk associated with transgenic plants. The latest publication is from the Pontifical Academy of Sciences [2]. There are also the results from 25 years of specific biosafety research, which did not reveal any novel risk. Also, there are the results from regulatory overviews of all the transgenic plants released into the environment. Finally, there is the practical experience from the use of GMOs for more than 16 years, on over 150 million hectares, and by up to 20 million farmers, with not a single documented case of harm. There is no other technology with such an unprecedented safety record. Specific GMO regulation may have been appropriate in the first years of exploration. Today, however, it is more than outdated. We had no idea what it meant to develop a product, what one has to consider with a GMO product, and where to find financial support for development of a humanitarian product. It did not take long to discover, that there are no funds beyond work for scientific novelty from academic or public resources. Product development is beyond the scope of academia. We had to find support from outside the public domain. This came finally from altruistic foundations. We also needed help with expertise in product development, and as it soon turned out, with intellectual property rights. So far we have, rightly, ignored patents and material transfer agreements (MTAs). None of this expertise was accessible in academia, therefore, we explored alternative approaches via the private sector. We tried to find support for our humanitarian project from the private sector. This finally led to a public–private partnership with Syngenta (http://www.syngenta.com). The basis was a deal with our vitamin A patent. A sublicense agreement enabled parallel exploitation for humanitarian and commercial use. The private sector received the rights for commercial exploitation in return for support for our humanitarian project. Dr. Adrian Dubock from Zeneca/ Syngenta was the architect of an agreement, which served as legal basis for all further developments. The key features were: (i) results from both parties are available for both projects; (ii) humanitarian use is restricted to subsistence farmers in developing countries; (iii) the humanitarian project is under the strategic guidance of the inventors, supported by a Humanitarian Board; and (iv) ‘Golden Rice’ is a donation of the inventors to resource-poor farmers (http://www.goldenrice.org). This public–private partnership solved the patent/MTA problem (over 70 patents and 20 MTAs). For all intellectual property rights that were effective for the humanitarian 132
Trends in Biotechnology March 2013, Vol. 31, No. 3
Table 1. Years spent following regulatory requirements Regulation Deletion of selectable marker Screening for streamlined integration Screening for regulatorily clean events Protection against liability problems Transboundary movement of seeds Obligatory sequence greenhouse field Permission for working in the field Requirement for one-event selection Experiments for the regulatory dosier Deregulation procedure
No. of years 2 2 2 1 2 1 2 2 4 1
project, the inventors received free licenses for humanitarian use. We had access to product development expertise from the company, acquired a professional project manager, and established a Humanitarian Board with all necessary expertise for our strategic decisions and a network of collaborating public rice research institutes in Asia (http:// www.goldenrice.org). The Golden Rice project continued with advice from the private sector and the board. The basic strategy was to avoid bad management and waste of resources and time by discovering at the end that there was something unacceptable in the product for regulatory authorities. Consequently, the project was streamlined according to the requirements of the deregulatory process. Thus, product development and deregulation took from 2000 to 2013 and required resources in the range of USD 30 million. So, what were the GMO-specific hurdles that made the process so time consuming and expensive? There is, of course, the continuous problem with the anti-GMO activists. We will ignore this problem here and focus on the technical obstacles. The major obstacles were: (i) development of regulatorily clean and agronomically attractive rice varieties; (ii) the requirement that all variety development be based on one single transgenic lead event; (iii) working under regulatory conditions; (iv) data collection for the regulatory dossier and deregulation; and (v) social marketing.
Box 1. Ramifications of GMO regulation GMO regulation delays use of GMO-based products for more than 10 years and carries a huge financial penalty. Time and costs for delivery of a GMO product to the market are so immense, that no public institution or any small or medium-sized private enterprise can afford the necessary investment. Numerous public GMO projects, including many from developing country laboratories and with orphan crops, will not make it to the market place. The damage to life and welfare is enormous. This affects the poor and not the rich Western societies responsible for the hostile antiGMO attitude. There is no scientific justification for the worldwide established GMO-specific regulatory system based on the concept of an extreme precautionary principle. There is, to the contrary, a moral imperative to make GMO technology available for public good such as nutrition security [2]. We waste a powerful technology for public good, if we do not revolutionize regulation from ideology-based regulation of the technology to science-based regulation of the trait [4].
Forum: Science & Society
Trends in Biotechnology March 2013, Vol. 31, No. 3
TRENDS in Biotechnology
Figure 1. Golden Rice (right) compared to normal rice. Reproduced, with permission, from the International Rice Research Institute.
Table 1 indicates how many years have been spent following regulatory requirements. Fortunately, they do not add up to 19 years, because regulations can be followed in parallel. The lessons learned from the Golden Rice project likely apply to all GMO projects initiated by public institutions for the public good. The present reality is that of a de facto monopoly for the use of the technology by a few financially potent companies with industrial crops and projects that
promise a return of not less than USD 100 million. There is no room for humanitarian or small projects with orphan crops for public good. This situation guarantees continued public hostility and plays into the hands of anti-GMO activists (Box 1). Golden Rice is at an advanced stage (Figure 1), and hopefully will be deployed from 2014 onwards, in The Philippines, where the International Rice Research Institute (IRRI) and PhilRice (http://www.philrice.gov.ph/) are developing local varieties. Moreover, with funding from The Rockefeller Foundation (www.rockefellerfoundation. org), USAid (http://www.usaid.gov/), and The Gates Foundation (http://www.gatesfoundation.org/), the project manager Dr. Gerard Barry is advancing deregulation of this leading Golden Rice event. This is of outstanding importance for the entire Humanitarian Golden Rice project worldwide because, according to the sublicense agreement under which all Golden Rice development proceeds, these regulatory data will be available for deregulation of all golden rice varieties based on the lead event and developed within the licensee network via traditional plant breeding from that event (http://www. irri.org/goldenrice). Forty grams of Golden Rice per day are sufficient to prevent the severe health consequences of vitamin A deficiency in rice-dependent poor populations [3]. The deployment of this life-saving technology was delayed for 12 years by nothing else but GMO regulation. To avoid a frequent misunderstanding: the blame is not on the regulatory authorities who, to our experience, have been very cooperative and efficient. The blame is on the rules and regulations and on those who maintain these regulations against better knowledge. References 1 Ye, X. et al. (2000) Engineering the pro-vitamin A pathway into (carotenoid-free) rice endosperm. Science 287, 303–305 2 Potrykus, I. and Ammann, K. (2010) Transgenic plants for food security in the context of development. Proceedings of a study week of the Pontifical Academy of Sciences. New Biotechnol. 27, 442–717 3 Tang, G. et al. (2012) Beta carotene produced by Golden Rice is as good as beta carotene in oil at providing vitamin A to children. Am. J. Clin. Nutr. 96, 658–664 4 Potrykus, I. (2010) Regulation must be revolutionized. Nature 466, 561 0167-7799/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tibtech.2012.11.008 Trends in Biotechnology, March 2013, Vol. 31, No. 3
133
Trends in Biotechnology March 2013, Vol. 31, No. 3
References 1 Kennedy, J. et al. (2010) Marine metagenomics: new tools for the study and exploitation of marine microbial metabolism. Mar. Drugs 8, 608–628 2 Costanza, R. et al. (1997) The value of the world’s ecosystem services and natural capital. Nature 387, 253–260 3 Oreskes, N. (2004) The scientific consensus on climate change. Science 306, 1686 4 Scannell, J.W. et al. (2012) Diagnosing the decline in pharmaceutical R&D efficiency. Nat. Rev. Drug Discov. 11, 191–200 5 Leal, M.C. et al. (2012) Trends in the discovery of new marine natural products from invertebrates over the last two decades – where and what are we bioprospecting? PLoS ONE 7, e30580 6 Mayer, A.M.S. et al. (2010) The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol. Sci. 31, 255–265 7 Lerman, J.A. et al. (2012) In silico method for modelling metabolism and gene product expression at genome scale. Nat. Commun. 3, 929 8 Markowitz, V.M. et al. (2012) IMG: the integrated microbial genomes database and comparative analysis system. Nucleic Acids Res. 40, D115–D122 9 Arnaud-Haond, S. et al. (2011) Marine biodiversity and gene patents. Science 331, 1521–1522 10 FAO (2012) The state of world fisheries and aquaculture 2012. In World Review of Fisheries and Aquaculture (http://www.fao.org/docrep/016/ i2727e/i2727e01.pdf) 11 Subhadra, B. and Grinson, G. (2011) Algal biorefinery-based industry: an approach to address fuel and food insecurity for a carbon-smart world. J. Sci. Food Agric. 91, 2–13 12 Davidson, W.S. et al. (2010) Sequencing the genome of the Atlantic salmon (Salmo salar). Genome Biol. 11, 403 13 Scott, S.A. et al. (2010) Biodiesel from algae: challenges and prospects. Curr. Opin. Biotechnol. 21, 277–286 14 Wargacki, A.J. et al. (2012) An engineered microbial platform for direct biofuel production from brown macroalgae. Science 335, 308–313 15 The Federal Government of Germany (2012) Biorefineries Roadmap (as part of the German Federal Government action plans for the material and energetic utilisation of renewable raw materials) (www.bmbf.de/ pub/roadmap_biorefineries.pdf)
Disclaimer statement The opinions expressed and arguments employed herein are those of the authors and do not necessarily reflect the official views of the OECD, or of the governments of its member countries.
0167-7799/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tibtech.2013.01.009 Trends in Biotechnology, March 2013, Vol. 31, No. 3
Special Issue: Celebrating 30 years of biotechnology
Unjustified regulation prevents use of GMO technology for public good Ingo Potrykus Emeritus Plant Sciences, Im Stigler 54, CH-4312 Magden, Switzerland
Transgenic plants are regulated for their technology because they have been claimed to lead to uncontrolled and unpredictable alterations of the genome and, therefore, to unpredictable risks to the environment and the consumer. This argument can, however, never justify regulation, because each technology used in plant breeding, so far, has exactly the same consequences. As a result of regulation, genetically modified organism (GMO) product develCorresponding author: Potrykus, I. ([email protected]).
opment is so expensive and time-consuming that it is beyond the capacity of public institutions and for public good. The statement above is one of the lessons from the author’s involvement in the ‘Humanitarian Golden Rice’ project (http://www.goldenrice.org). The research teams of Ingo Potrykus and Peter Beyer worked from 1991 onwards on the problem of vitamin A deficiency in rice-dependent populations. As a solution, they engineered the biosynthetic pathway for provitamin A into rice endosperm. They 131
Forum: Science & Society achieved proof-of-concept in 1999 [1]. ‘Vitamin A rice’ to date is possible only via genetic engineering. To have a practical impact, a scientific result needs to be converted into a product that can be handed out to the needy. Since 2000 the inventors of Vitamin A rice have been working on that task and they have learned many lessons, which, probably, are not familiar to colleagues from academia. A few of those lessons will be presented below. Why do we state ‘unjustified’ GMO regulation? There is broad scientific consensus, which has been published widely by academic and other public institutions, that there is no specific risk associated with transgenic plants. The latest publication is from the Pontifical Academy of Sciences [2]. There are also the results from 25 years of specific biosafety research, which did not reveal any novel risk. Also, there are the results from regulatory overviews of all the transgenic plants released into the environment. Finally, there is the practical experience from the use of GMOs for more than 16 years, on over 150 million hectares, and by up to 20 million farmers, with not a single documented case of harm. There is no other technology with such an unprecedented safety record. Specific GMO regulation may have been appropriate in the first years of exploration. Today, however, it is more than outdated. We had no idea what it meant to develop a product, what one has to consider with a GMO product, and where to find financial support for development of a humanitarian product. It did not take long to discover, that there are no funds beyond work for scientific novelty from academic or public resources. Product development is beyond the scope of academia. We had to find support from outside the public domain. This came finally from altruistic foundations. We also needed help with expertise in product development, and as it soon turned out, with intellectual property rights. So far we have, rightly, ignored patents and material transfer agreements (MTAs). None of this expertise was accessible in academia, therefore, we explored alternative approaches via the private sector. We tried to find support for our humanitarian project from the private sector. This finally led to a public–private partnership with Syngenta (http://www.syngenta.com). The basis was a deal with our vitamin A patent. A sublicense agreement enabled parallel exploitation for humanitarian and commercial use. The private sector received the rights for commercial exploitation in return for support for our humanitarian project. Dr. Adrian Dubock from Zeneca/ Syngenta was the architect of an agreement, which served as legal basis for all further developments. The key features were: (i) results from both parties are available for both projects; (ii) humanitarian use is restricted to subsistence farmers in developing countries; (iii) the humanitarian project is under the strategic guidance of the inventors, supported by a Humanitarian Board; and (iv) ‘Golden Rice’ is a donation of the inventors to resource-poor farmers (http://www.goldenrice.org). This public–private partnership solved the patent/MTA problem (over 70 patents and 20 MTAs). For all intellectual property rights that were effective for the humanitarian 132
Trends in Biotechnology March 2013, Vol. 31, No. 3
Table 1. Years spent following regulatory requirements Regulation Deletion of selectable marker Screening for streamlined integration Screening for regulatorily clean events Protection against liability problems Transboundary movement of seeds Obligatory sequence greenhouse field Permission for working in the field Requirement for one-event selection Experiments for the regulatory dosier Deregulation procedure
No. of years 2 2 2 1 2 1 2 2 4 1
project, the inventors received free licenses for humanitarian use. We had access to product development expertise from the company, acquired a professional project manager, and established a Humanitarian Board with all necessary expertise for our strategic decisions and a network of collaborating public rice research institutes in Asia (http:// www.goldenrice.org). The Golden Rice project continued with advice from the private sector and the board. The basic strategy was to avoid bad management and waste of resources and time by discovering at the end that there was something unacceptable in the product for regulatory authorities. Consequently, the project was streamlined according to the requirements of the deregulatory process. Thus, product development and deregulation took from 2000 to 2013 and required resources in the range of USD 30 million. So, what were the GMO-specific hurdles that made the process so time consuming and expensive? There is, of course, the continuous problem with the anti-GMO activists. We will ignore this problem here and focus on the technical obstacles. The major obstacles were: (i) development of regulatorily clean and agronomically attractive rice varieties; (ii) the requirement that all variety development be based on one single transgenic lead event; (iii) working under regulatory conditions; (iv) data collection for the regulatory dossier and deregulation; and (v) social marketing.
Box 1. Ramifications of GMO regulation GMO regulation delays use of GMO-based products for more than 10 years and carries a huge financial penalty. Time and costs for delivery of a GMO product to the market are so immense, that no public institution or any small or medium-sized private enterprise can afford the necessary investment. Numerous public GMO projects, including many from developing country laboratories and with orphan crops, will not make it to the market place. The damage to life and welfare is enormous. This affects the poor and not the rich Western societies responsible for the hostile antiGMO attitude. There is no scientific justification for the worldwide established GMO-specific regulatory system based on the concept of an extreme precautionary principle. There is, to the contrary, a moral imperative to make GMO technology available for public good such as nutrition security [2]. We waste a powerful technology for public good, if we do not revolutionize regulation from ideology-based regulation of the technology to science-based regulation of the trait [4].
Forum: Science & Society
Trends in Biotechnology March 2013, Vol. 31, No. 3
TRENDS in Biotechnology
Figure 1. Golden Rice (right) compared to normal rice. Reproduced, with permission, from the International Rice Research Institute.
Table 1 indicates how many years have been spent following regulatory requirements. Fortunately, they do not add up to 19 years, because regulations can be followed in parallel. The lessons learned from the Golden Rice project likely apply to all GMO projects initiated by public institutions for the public good. The present reality is that of a de facto monopoly for the use of the technology by a few financially potent companies with industrial crops and projects that
promise a return of not less than USD 100 million. There is no room for humanitarian or small projects with orphan crops for public good. This situation guarantees continued public hostility and plays into the hands of anti-GMO activists (Box 1). Golden Rice is at an advanced stage (Figure 1), and hopefully will be deployed from 2014 onwards, in The Philippines, where the International Rice Research Institute (IRRI) and PhilRice (http://www.philrice.gov.ph/) are developing local varieties. Moreover, with funding from The Rockefeller Foundation (www.rockefellerfoundation. org), USAid (http://www.usaid.gov/), and The Gates Foundation (http://www.gatesfoundation.org/), the project manager Dr. Gerard Barry is advancing deregulation of this leading Golden Rice event. This is of outstanding importance for the entire Humanitarian Golden Rice project worldwide because, according to the sublicense agreement under which all Golden Rice development proceeds, these regulatory data will be available for deregulation of all golden rice varieties based on the lead event and developed within the licensee network via traditional plant breeding from that event (http://www. irri.org/goldenrice). Forty grams of Golden Rice per day are sufficient to prevent the severe health consequences of vitamin A deficiency in rice-dependent poor populations [3]. The deployment of this life-saving technology was delayed for 12 years by nothing else but GMO regulation. To avoid a frequent misunderstanding: the blame is not on the regulatory authorities who, to our experience, have been very cooperative and efficient. The blame is on the rules and regulations and on those who maintain these regulations against better knowledge. References 1 Ye, X. et al. (2000) Engineering the pro-vitamin A pathway into (carotenoid-free) rice endosperm. Science 287, 303–305 2 Potrykus, I. and Ammann, K. (2010) Transgenic plants for food security in the context of development. Proceedings of a study week of the Pontifical Academy of Sciences. New Biotechnol. 27, 442–717 3 Tang, G. et al. (2012) Beta carotene produced by Golden Rice is as good as beta carotene in oil at providing vitamin A to children. Am. J. Clin. Nutr. 96, 658–664 4 Potrykus, I. (2010) Regulation must be revolutionized. Nature 466, 561 0167-7799/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tibtech.2012.11.008 Trends in Biotechnology, March 2013, Vol. 31, No. 3
133