• Evolution of GM crop development – from the 1990s to today; • Future challenges: • Pipeline products; • Next generation GMOs and impacts on seed testing ISTA meeting, Montevideo, 2015 Dr. Ray Shillito, Bayer CropScience, USA Page 1 Evolution, Pipeline and Future of Biotech- 2015 From the 1990s 1970’s to today; Page 2 Evolution, Pipeline and Future of Biotech- 2015 Three key elements led to the first developments in Ag. Biotech Agrobacterium tumefaciens Plant Tissue Culture Molecular Biology and Biochemistry Page 3 Evolution, Pipeline and Future of Biotech- 2015 The Initial Development of Plant Biotechnology occurred in the 70’s and 80’s in both the EU and USA. Page 4 Evolution, Pipeline and Future of Biotech- 2015 Critical Technologies 1869 - DNA 1972 – Discovery of restriction enzymes discovered – DNA cloning 1953 1994 – Agro transformation - Structure of of Monocots DNA solved Moratorium – 1974 -75 1928 1975 - Southern blotting – demonstration of 1976 1984 – Oligomer biosynthesis bacterial – DNA Sequencing transformation 1987 – Gene Gun 1983 PCR invented Agrobacterium- transformation using disarmed vectors Transformation without Agrobacterium Page 5 Evolution, Pipeline and Future of Biotech- 2015 Some of the Technologies with Direct Impact Selectable markers Tissue culture Protoplasts/PEG/electroporation Agrobacterium tumefaciens Biolistics Whiskers PCR Agrobacterium in monocots Codon optimization A188 (3 way sweet corn cross) Antisense / RNAi Bt proteins Cre/Lox etc. Page 6 Evolution, Pipeline and Future of Biotech- 2015 The view from 1996 was like this.. Page 7 Key US Regulatory Approvals of Biotech Products 1992 – FlavrSavr Tomato FDA 1994 – Bt176, (EPA), 1995 (USDA, FDA) 1994 – Bromoxynil cotton 1994 – RR soybean (USDA), 1995 (FDA) 1995 - NewLeaf Potato, USDA, EPA, FDA 1995 – T25 LL Corn 1995 – RR Canola 1995 – Mon810 (USDA, EPA), 1996 (FDA) 1996 – Papaya, Bt11 1998 – InVigor Canola (1996 in Canada) 1998 – RR Sugarbeet (FDA), 2005 (USDA) 1999 – LL62 Rice Page 8 Evolution, Pipeline and Future of Biotech- 2015 Biotech Products and Cultivation in Europe – Key Events 1997 Bt 176 Approved for cultivation 1998 Mon810 and T25 Approved for cultivation Food safety issues as a driver: 1996 - First case of Mad cow disease in Europe 1999 - Dioxin contamination (animal feed) scandal hits Belgium 1999 - Coke products withdrawn in Belgium due to bad CO2 EU Moratorium on approvals – 1998 - 2004 2010 Amflora potato approved for cultivation Page 9 Evolution, Pipeline and Future of Biotech- 2015 Products that have come and Gone Although Approved – Consumers may never see a product – or not for long Demand for the FLAVR SAVR tomato was high and remained high, but the product was never profitable (because it wasn’t in the right varieties and was difficult to get to market) Page 10 Evolution, Pipeline and Future of Biotech- 2015 Page 11 Evolution, Pipeline and Future of Biotech- 2015 Page 13 Evolution, Pipeline and Future of Biotech- 2015 Global Area (Million Hectares) of Biotech Crops, 2014: by Country Diversity of Biotech Products Others Major Biotech Crops 1% Maize Canola Soybean 9% Cotton Cotton Canola 14% Soybean Other Biotech Crops 50% Sugar beat Alfalfa Maize Papaya 30% Eggplant Squash Potato Melon Sugarcane Wheat Clara Rubenstein, Pioneer, a DuPont Company Global Adoption Rates (%) for Principal Biotech Crops (Million Hectares, Million Acres), 2014 Value (USD Value (USD Country Country million) million) USA 12,000 Morocco 140 China 9,950 Switzerland 140 France 2,800 Bulgaria 120 Brazil 2,625 Chile 120 Canada 2,120 Nigeria 120 India 2,000 Serbia 120 Japan 1,350 Slovakia 110 Seed Germany 1,170 New Zealand 100 Argentina 990 Uruguay 96 testing is Italy 767 Ireland 80 important Turkey 750 Paraguay 80 Spain 660 Portugal 80 Netherlands 590 Algeria 70 6 of the top 10 Russian Federation 500 Kenya 60 United Kingdom 450 Iran 55 commercial South Africa 428 Israel 50 markets for Australia 400 Tunisia 45 seed are Republic of Korea 400 Bolivia 40 Mexic o 350 Colombia 40 growing Czech Republic 305 Slovenia 40 Biotech crops Hungary 300 Peru 30 China, Taiwan 300 Zimbabwe 30 Poland 280 Malawi 26 Sweden 250 Libya 25 Romania 220 Saudi Arabia 20 Denmark 218 Zambia 20 Data from: Greece 200 Philippines 18 Belgium 185 Ecuador 15 ISF 2014 Finland 160 Tanzania 15 ISAAA 2014 Austria 145 Uganda 10 Egypt 140 Dominican Republic 7 Total USD 44,925 million (2013 figures) The commercial world seed market is assessed at approx. USD 45 billion Page 18 Evolution, Pipeline and Future of Biotech- 2015 Pipeline Products Page 19 Evolution, Pipeline and Future of Biotech- 2015 Challenges for Agri-Businesses Limited arable Safeguard and increase yields from constant land area land coupled à with rising better resource management (targeted use of crop protection, irrigation technology and fertilizers) demand à increase yields through innovative technologies (hybridization, plant biotechnology) Expand agricultural production in marginal areas à new crops with greater tolerance of drought and extreme temperatures Climate change Increase tolerance of plants to climatic variability à develop new varieties using state - of - the - art technologies à improve plant health and nutrient uptake Research and innovation are the key to mastering the challenges of the New Ag Economy Page 20 Evolution, Pipeline and Future of Biotech- 2015 Industry investing in multiple modes of action, 1996-2020 (as of 2014) WEED CONTROL ABOVE GROUND PESTS BELOW GROUND PESTS CORN ü Glufosinate-tolerance ü Caterpillar protection Gen1 ü Rootworm protection Gen1 ü Glyphosate-tolerance ü Caterpillar protection Gen2 ü Rootworm protection Gen2 ü Imidazolinone-tolerance ü Caterpillar protection Gen3 ü Rootworm protection Gen3 ü 2,4-D tolerance q Caterpillar protection Gen4 q Rootworm protection Gen1 q FOP tolerance SOYBEANS ü Glufosinate-tolerance ü Caterpillar protection Gen1 q Soybean cyst nematode ü Glyphosate-tolerance ü Caterpillar protection Gen2 protection ü Sulfonylurea-tolerance q Stink bug protection q Dicamba tolerance q Glufosinate-tolerance Gen2 q HPPD tolerance q PPO tolerance COTTON ü Glufosinate-tolerance ü Bollworm protection Gen1 ü Root knot nematode ü Glyphosate-tolerance ü Bollworm protection Gen2 protection Gen1 q 2,4-D tolerance ü Bollworm protection Gen3 q Reniform nematode q Dicamba tolerance q Bollworm protection Gen4 protection q HPPD tolerance q Lygus protection q Root knot nematode protection Gen2 ü Commercial offering q Future or potential offering Page 22 Evolution, Pipeline and Future of Biotech- 2015 Page 23 Evolution, Pipeline and Future of Biotech- 2015 Page 24 Evolution, Pipeline and Future of Biotech- 2015 Page 25 Evolution, Pipeline and Future of Biotech- 2015 Page 26 Evolution, Pipeline and Future of Biotech- 2015 Page 27 Evolution, Pipeline and Future of Biotech- 2015 Page 28 Evolution, Pipeline and Future of Biotech- 2015 There are a lot of Events/Products! Crop Commer JRC Possible Approved Approved cial Projected Commercial historically for historically Events Commercial products in cultivation (inc for food (inc in 2008 Events in 2014 stacks) stacks) 2015 Soybean 1 17 ~10 28 28 Maize 9 24 ~71 91 131 Canola 4 10 ~11 25 32 Cotton 12 27 ~30 46 43 Rice 0 15 2 7 5 Potatoes 0 8 0 31 41 Other 7 23 ~11 35 33 Crops Flowers - - 22 22 0 Total Source:33 JRC Report, 2009124 / ISAAA ~157 285 312 ISAAA plus OECD database has 222 unique event entries The wealth of new events has implications for ISTA members OECD (2013) ENV/JM/MONO(2013)19 Since it may be impossible to entirely eliminate LLP in seed, in some cases thresholds have been set to assure an acceptable and predictable supply of seeds. This has been in response to several instances where the LLP was detected at such a low level that it was technically below the level of quantification using validated protocols for testing. In these situations, testing at different stages in the seed distribution system led to conflicting results regarding the presence of LLP in seed. Recognizing the inability to entirely eliminate LLP, thresholds have also been adopted by some importing countries to avoid the reduced availability of seeds in cases where it was known that the unauthorized plant had been authorized at least in one other country. The International community is discussing the issue of LLP in seeds The International Statement on Low Level Presence 12. Recognize that LLP of unapproved seed in commercial channels is also a challenge to seed trade and that it also requires collaborative efforts to address. Further collaborative efforts on seed through this initiative should be informed by the work being currently undertaken by the Organization for Economic Cooperation and Development (OECD) in this area List of countries endorsing the International Statement on Low Level Presence (2012) Australia, Argentina, Brazil, Canada, Chile, Costa Rica, Mexico, Paraguay, Philippines, Russia, United States, Uruguay, Vietnam. Detection of unknowns is difficult Knut Heller, Genetically Engineered Food – Methods and Detection, 2nd Edition, Wiley, 2006 GM testing – which events? • New events originating from major biotechnology providers • New events arising from other sources • “Other events” • Stacked events • Need efficient screening, identification and quantification methods which o are easily adaptable to the ongoing developments and o which can be easily introduced to existing laboratory infrastructures and testing schemes ‘Detection’ of ‘stacks’ – not possible Each individual event in a GM stack has a DNA or protein- based detection method The inserted DNA of different events is usually located on different chromosomes or many millions of base-pairs apart on the same chromosome Event-specific PCR cannot bridge gaps greater than a few hundred base-pairs Therefore it is not possible with present technology to develop a molecular technique that ‘detects the stack’ cf: recent EU study on analysis of stacks Page 34 Evolution, Pipeline and Future of Biotech- 2015 Next generation GMOs and impacts on seed testing Page 35 Evolution, Pipeline and Future of Biotech- 2015 New events are now arising from sources other than major biotech providers These come from small companies and/or government research.