In developing countries children per year go blind and up to per day die from vitamin A-malnutrition. And this will continue year by year, if we do not complement traditional interventions.

Biotechnology: Possibilities, Risks, Ethics and Society Stockholm, 24 August Genetics to change the nutritional composition – the golden rice case. GMO-technology enables to nutritionally optimise food security crops, but extreme precautionary regulation prevents the use of this technology in public goods projects to the benefit of the poor in developing countries. Ingo Potrykus Professor em., Institute of Plant Sciences, ETH, Zürich, Switzerland.

Genetic engineering can provide traits, which are not easily available with traditional means. Vitamin A-rice was, and is, not possible without genetic engineering. Even unpolished rice does not contain provitamin A. Why genetic engineering in addition to the traditional interventions? Traditional interventions are effective, but not effective enough. Statistics show that, despite enormous efforts and investments in traditional interventions, we are still faced with 500‘000 blind children caused by vitamin A- deficiency. And there are larger malnutrition problems for e.g. iron, zinc and other micro nutrients.

Restriction enzymes: a) I-sce I, b) Kpn I. Probe: psy Restriction enzymes: a) I-sce I, b) Kpn I. Probe: crt I Restriction enzymes: a) I-sce I, b) Spe I. Probe: cyc I-sce I Kpn I Spe I Reconstruction of  -carotene Biosynthetic Pathway in Rice Endosperm by Agrobacterium-Mediated Transformation kb kb kb psyGt1 prnos!35S pr crtI nos! RBLB 35S! aph 4cyc 35S! 35S prGt1 pr LBRB pZcycH pZPsC GGPP Phytoene Lycopene  -Carotene phytoene synthase phytoene desaturase lycopene cyclase

 lycopin-cyclases Phytoene-synthase Phytoene-desaturase  Carotin-desaturase Hydroxylase Epoxidase Neoxanthin-synthase Erwinia crtI Towards Nutritional optimization of rice: Iron bio-availability:  Ferritin, Phytase, Cystein High-quality protein:  Arg, His, Ile, Leu, Lys, Met, Phe, Thr. Trp, Val Carotenoids:   -carotene,lutein, zeaxanthin Vitamin E   Vitamin A  -Oryzanol   Lipids ?  Other ?

„Golden Rice“ contains the genes necessary to activate the biochemical pathway for provitamin A. The intensity of the colour represents the concentration.

„Humanitarian Project“: „Golden Rice“ is a public project. It was designed to reduce malnutrition in developing countries. With support from industry - in a public/private partnership with Syngenta -Golden Rice will be made available to subsistence farmers in developing countries free of charge and limitations. It will be their property and they will use part of their harvest for the next sowing. There will be no new dependencies. Farmers will use their traditional farming systems and they will not require any additional input.

Philippines: International Rice Research Institute (IRRI) Philippines: National Rice Research Institute (PhilRice) Vietnam: Cuu Long Delta Rice Research Institute India: Department of Biotechnology, New Delhi (DBT) India: Directorate of Rice Research, Hyderabad (DRR) India: Indian Agricultural Research Institute, Delhi (IARI) India: University of Delhi South Campus (UDSC) India: Tamil Nadu Agricultural University (TNAU) India: Agricultural University Pantagar (GBPUAT) India: University of Agricultural Sciences Bangalor Bangladesh: Bangladesh Rice Research Institute China: Huazhong Agricultural University, Wuhan China: Chinese Academy of Sciences, Beijing China: Yunnan Acad. Agri. Sciences, Kunming Indonesia: Agency for Agricultural Res.& Dev., Jakarta Germany: University of Freiburg Humanitarian GoldenRice Network With technical support from Syngenta South Africa: CSIR, Pretoria, sorghum, maize.

 Intellectual Property Rights 2000   Material Transfer Agreements 2001   Freedom-to-Operate 2001   GMO-Competent Partner   Transfer to Indica varieties 2002   „Regulatory Clean Construct“ 2002   „Regulatory Clean Events“ 2003   „Regulatory Clean“ line at 3.2  g/g 2003   First field assessments April-September 2004   Experimental lines at substantially higher levels  History of GoldenRice development Science  1980 – Technology Development  Product developent 1999 – 200?    Deregulation !!!

1 seed  1 plant  seeds / 20 g  seeds / 20 kg  seeds / 20 t  seeds / t Each seed has the potential to produce in two years food for for one year and poor......and to carry the technology......to reduce malnutrition in a sustained and cost- effective manner. All a farmer needs, to benefit from the technology, is one seed. The potential of 1 GoldenRice rice seed GMO-regulation alone prevents the farmers accessing this potential. In 2 years from 1 seed to t !

Why do we have ‚GMO-regulation‘? History: precaution – unpredictable genome alterations. Experience: no specific risks associated with GMO‘s. Why do we maintain ‚extreme precautionary‘-regulation? „To built trust for acceptance of GMO‘s.“ Experience: this does not and can not work. Why do we not skip the ‚extreme precautionary‘ approach ? Under the present hysteria nobody has the power to do so? What price are developing countries paying? GMO-technology will not help to reduce hunger & malnutrition, and will not contribute to protection of the environment in developing countries.

IR 64 Breeding tree for Indica variety IR64                    Crossing &  Unpredictable & most extensive genome alterations and their accumulation at every single New varieties

IR 64 Breeding tree for Indica variety IR64                     @ Unpredictable & most extensive genome alterations and their accumulation at every single step. The blue box represents the ‚natural‘ rice genome; the barrs indicate the genetic changes underlying the,traditional‘ development to a modern rice variety Mutations Recombinations Translocations Deletions genetically modified genome Every modern variety in every crop is intensly „genetically modified“, and unregulated!

Breeding tree for ‚Golden‘ IR64                     @ Mutations Recombinations Translocations Deletions Golden IR 64 IR 64 One relatively precise & defined & minor change in the IR64 genome: why extrem deregulation requirements?! genetically modified genomegenetically engineered genome

Effect of an ‚extreme precautionary approach to regulation‘ on public goods research for food security in developing countries: There are numerous scientists and in public institutions which have capacity, funding and motivation to apply GM- science successfully to problems in food security. Very few of those have the capacity, understanding and know-how to develop a product from scientific insight. Probably, no public institution has the resources, experience, and motivation to carry a single GMO product accross the hurdles of todays regulatory procedures. Even with support from the private sector, deregulation of a novel GMO event has become an astronomic task. If we continue with present regulatory standards, the potential of GM technology for humanitarian uses will not reach the poor!

January 2004, ISBN

‚The European Union is ignoring a „moral imperative“ to promote genetically modified crops for their great potential for helping the developing world.‘ ‚We believe EU regulators have not paid enough attention to the impact of EU regulations on agriculture in developing countries.‘ ‚The current evidence from safety assessments of GM crops does not suggest any significant risk to people who eat them.‘ (and to the environment). ‚An excessively conservative interpretation of the precautionary approach... is fundamentally at odds... and essentially impractical.‘ ‚To hold to the most conservative interpretation of the precautionary approach invokes the fallacy of thinking that the option of doing nothing is itself without risk.‘

GMO-technology enables to nutritionally optimise food security crops, but extreme precautionary regulation prevents the use of this technology in public goods projects to the benefit of the poor in developing countries.

 The present radical application of the ‚precautionary principle‘ is immoral. It leads to defined, predictable, and dramatic damages to life, health, and biodiversity. All risks claimed, so far, inherent to GMO-technology are, in comparison, minor and they are just hypothetical.  Regulatory regimes affected by this attitude lead to an astronomic waste of financial, intellectual and mental resources. They are scientifically unjustified, and they prevent the use of GMO-technology in public goods projects and not in industrial ones.  Those with power in the public & political domain ignoring these facts, those fighting the technology for a political agenda, and those insisting in extreme precautionary regulations, share responsibility for future unnecessary suffering and death of millions.

In the early 19th century a Thai princess celebrated her 18th birthday. She fell into the palace pond and drowned in front of hundreds of guests. Nobody helped her out of the water. Why? It was „taboo“ to touch a member of the „divine“ royal family! We believe that we would have saved the princess, however...

In the early 21st century 500‘000 children per year become blind and 6‘000 per day die from vitamin A-malnutrition. This could be prevented with the help of „GMO‘s“. However GMO‘s are „taboo“ for our society which prefers to trust „phantom risks“ instead of scientific evidence.

 RDA (Recommended Daily Allowance): 0.3 mg/day for 1-3 year old child, based on 4-month body store.  The average amount needed to prevent deficiency state is ½ of that needed for adequate storage (0.15 mg/day).  Conversion factor to RAE (Retinol Activity Equivalents) is for fruits and vegetables 12:1; for  -carotene in oil 2:1.  100 g Golden Rice contain 0.16 mg  -carotene, stored in lipid membranes (possibly most comparable to oil).  The amount of available vitamin A depends upon bioavailability (absorption and bioconversion).  Golden Rice has a simple and disgestible food matrix. Assuming, therefore, a 2:1 conversion, 100 g of Golden Rice may provide 50% of the total vitamin A required.  This hypothesis will be tested, with financial support from NIH, by the USDA Human Nutrition Laboratory, in China. How much Golden Rice has a child to eat to defeat vitamin A-deficiency?  200 g/day may be sufficient, but we will know only after nutritional studies have been completed.