Biotech Traits & Technologies for Future Ag-Sustainability

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1 EPSO Workshop Plant Productivity for Food, Ghent, 7-8 September 2009 Biotech Traits & Technologies for Future Ag-Sustainability Michael Metzlaff Bayer BioScience

2 Bayer CropScience: One of Three Subgroups of Bayer Management Holding Company Bayer AG Board of Management Bayer HealthCare Bayer CropScience Bayer MaterialScience Bayer Business Services Bayer Technology Services Currenta Business Area Companies Service Companies

3 The Bayer BioScience Business The seed and trait business of Bayer CropScience Crop Protection Harnessing plant biotechnology and other modern breeding techniques to deliver: BioScience Bayer CropScience Environmental Science Improved crop quality Stabilization and increase of yields Sustainable plant-based solutions to meet increasing global needs for food, feed, fiber & fuel

4 years of plant domestication Osiris Egyptian God of vegetation and death

5 The Challenges for the Agriculture of Tomorrow Growing world population increasing food & energy demand decreasing farmland per capita Need for alternative energy feedstocks increasing demand for renewable energy and biofuel Growing wealth Climate change increasing meat consumption and need for feed decreasing stocks to use Acreage competition between food, feed, bio-energy crops and fiber Urgent need for increased agricultural productivity yield losses through adverse weather conditions need to reduce greenhouse gas emissions, such as CO 2

6 If this would be the Earth (Surface of 50.9 billion ha) this would be the land available for agriculture (1.5 billion ha / ~ 3 %) Source: Illustration from CropLife America, adapted by Bayer CropScience

7 Developing Seeds that Deliver Solutions Success Factors for a quality seed offering Breeding tools Trait/biotech research Quality Seed offering Germplasm

8 R&D Guidelines from Market Area Business Plans Business defines the needs for new traits (defensive and/or differentiating) Translation into a portfolio of research programs for defined traits/crops 1,000 Revenues (M )* Turn-over without Research output Differentiating Quality Traits Must Have Agronomic Traits

9 Innovation requires Public-Private-Partnerships Research Breeding & Development Discovery Technology Testing Commercial Concept Testing Development Discovery Innovation Application Public Sector Yield Potential Yield Stability Genome Engineering Quality Enhancement Genetics BioInformatics-Trait Testing-BioAnalytics Breeding Development

10 Abiotic Stress Innovation PCT Patent Applications Abiotic Stress Tolerance Trait applications DD DAS BASF SYT MON BAY others academia Source: IP analysis Rolf Deblaere, BBS Gent Recent and dramatic increase in abiotic stress research Majority of Patents filed by academia

11 Way Forward Public Private Partnerships ( Win-Win Situation ) Academia & Public Sector Market A win when industrial know-how flows back to society Creativity in areas with consumer relevance Increased appreciation of plant science Spin-out of start-up companies with new jobs D 0-6 yrs to mark et R 6-12 yrs to mark et Current industry R&D portfolio Future R&D portfolio based on selected System Biology platforms Private Sector A win when innovations are incorporated at lower risk Realistic views on opportunity & timing Minimal time-to-market Abiotic stress, Water Use Efficiency, Renewable Energy, Chemical Precursors, Predictive Gene Mode-Of-Action Win-win requires alignment Common strategic view Geographic proximity

12 Technology Integration Strategy Business dictates a Licensing-In - driven R&D strategy Technology Integration aims to: Fill innovation pipeline to satisfy launch requirements Order of preference: validated traits, non-validated traits, discovery leads Technology providers: R&D start-up companies, competitors, academia & institutes Benefits: Reduce risk and timelines, and broaden scope of innovation fields Our current way of working: Licensing in of leads from academia and start-ups Stimulating leading scientists to validate leads from their discovery with us Participating in pre-competitive public-private discovery consortia To be a respected forward integrator for academia To direct academia to focus on relevant topics In-house discovery activities are complemented by licensing-in to: Reduced risk and time-lines in pipeline Public-Private Consortia Reduce costs (45% cost saving in Discovery) In-house discovery activities primarily serve to: Explore new strategic trait innovation opportunities Fill in pipeline gaps Understand science field to be best-in-class integrator Discovery Licensing in leads & traits Technology Testing Funding of Collaborators Commercial Concept Testing Green Trait Product or Seed Development

13 The Actual Trait Pipeline: Lead R&D Projects at Bayer BioScience Research Early development Advanced development Prelaunch Launch (E) 2015 >2013 > /2010 No. Projects ~ Projects Herbicide- Herbicide- Herbicide- Herbicidetolerance tolerance tolerance tolerance: Insect- Insect- Insect- In-house GlyTol control control control (cotton) Quality traits Quality traits Cotton GlyTol x LL (cotton) Disease control Disease control Canola LL (soybean) Stress tolerance Yield increase Soybean Rice Promising BioScience pipeline to face the challenges of tomorrow Range of new high impact traits in research

14 R&D Process GM and non-gm process Phases Discovery Phase 1 Phase 2 Phase 3 Phase 4 GM Name Discovery Technology Testing Commercial Concept Testing Final Elite Event Selection Advanced Development / Pre Launch Milestone Gene Identified and Accessed Technology Proof of Concept Commercial Proof of Concept Elite Event Selected Ready for launch Duration (y) ~ y Non GM Name Discovery Technology Testing Commercial Concept Testing Final Elite Allele Combination Selection Advanced Development / Pre Launch Milestone Target loci or parental lines identified Technology Proof of Concept Commercial Proof of Concept Elite Allele Combination Selected Ready for launch Duration (y) y* *Qualitative (7-12 y) and quantitative traits (11-18 y)

15 The yield gap Cold Drought Salinity Abiotic Stresses (& remaining Biotic Stresses) Heat Drought High Light attainable yield Acclimation & Adaptation Yield gap actual yield

16 Cotton Abiotic Stress Tolerance: Case Study Cotton is sensitive to various abiotic stresses throughout the season Emergence First square First bloom Peak bloom Open boll Cold Drought Heat Cold Slow development, Slow development, Poor fertilization, Slow boll development, uneven stand square and boll drop boll drop reduced quality

17 The PARP and NAD+ Salvage Pathway

18 Drought Tolerance of RNAi-PARP Lines in the Field control control control RNAi-PARP line RNAi-PARP line Abiotic Stress Tolerance: Field trial harvest show significantly higher yield compared to control

19 Increased Biomass Production in Plants Expressing E.coli GDH WT DEF GT-DEF 400 *** root dry weight (mg) *** 0 WT DEF GT-DEF

20 Imidacloprid as Biotic and Abiotic Stress Shield Cl N N Imidacloprid N N H NO 2 O Cl O N 6-Chloro nicotinic acid the chloropyridine side chain of Imidacloprid is cleaved in-vivo resulting in 6-chloronicotinic acid (6-CNA) as the major degradation product 6-CNA is known to act as systemic signal transmitter (elicitor) leading to the formation of PR-proteins comparable to the plant own signal transmitter salicylic acid PR-proteins aiding plants against infection by fungi, bacteria and viruses

21 NAD+ salvage pathway + imidacloprid

22 Sources of High Impact Traits for Commodity Crops Natural Variation: Traditional Breeding Exploiting existing variation Genetic Engineering: Novel alleles Changing the code (Hardware Changes) Expression Engineering: Novel expression patterns Altering expression (Software Changes) Change focus of breeding from selection to design: What can we do? What do we want the plant to be? Primary Germplasm Secondary Germplasm Tertiary Germplasm

23 The same genotype may result in many different phenotypes Energy use efficiency Energy use efficiency Isogenic line Genotype Epigenotype Energy use efficiency Energy use efficiency Energy use efficiency Energy use efficiency Energy use efficiency

24 Each plant in a population has a specific energy use efficiency that is heritable Energy use efficiency

25 Methylation sensitive AFLP analyses reveal changes in the epigenetic status Simon high EUE low EUE

26 The epigenetic improved hybrids grow faster and are more vigorous control hybrid improved hybrid

27 Central Role of NAD+ (PNAS 104: , 2007)

28 System Sudoku = 10 = 10 = 10 = = 10 = 10 = «Plants Systems Biology has to enable mathematic modelling of dynamic networks underlaying crop productivity and sustainability» 32 = 10 = 10 = = = 10 = 10 = 10 = 10 = 10

29 The industry R&D challenge Build a sustainable pipeline From in-house discovery From research collaborations with academia («PPP») Exploiting diversity in native genes Licensing-in leads from start-up companies, institutes, and universities Timely implementation of enabling technologies Molecular Breeding & Epigenetics BioInformatics Reverse genetics platform Systems Biology Gene replacement, Controlled gene expression, Non-destructive phenotyping (HTP and precision) «Benefit research» (water, nutrient input, carbon footprint, biodiversity ) Doubling BioScience R&D resources to build a sustainable pipeline

30 Plant Biotechnology will drive Industry Redefinition Crop Protection Traits reshape industry structure Seed / Trait / Agrochemical bundles drive Crop Protection market Molecular Breeding rejuvenates Variety Breeding Systems Biology drives plant-based specialty products Systems Biology and Gene Replacement drive crop yield & plant-based products Revisit of breeding machinery Diversification of output Production optimization Redefinition of industry

31 There is a Need for a Second Green Revolution While global demand for agricultural products continues to rise limited arable land, decreasing growth rates of crop yield, water shortages and climate change create enormous challenges on the supply side To meet these demands now and in the future, we need nothing less than a second green revolution : Raising agricultural productivity with the help of improved crop varieties, plant biotechnology and innovative crop protection solutions Enhanced public investments into agricultural infrastructure

32 Will there be a strong European Ag Biotech sector? Europe needs to make a choice Agriculture is a Global Business Plant Biotechnology will revolutionize industry, regardless of which stance the European countries will take Europe still has the choice Train the scientists who then leave and work where the conditions to implement their work are more favourable Become just an importer of food, feed and renewable raw materials produced elsewhere in the world or Participate actively in the value creation of Agri-business Add new options for sustainable use of farmland Europe needs policy coherence on plant biotechnology To benefit from research and market potential in Europe To build a European basis for innovation led growth in Agriculture

33 Thank you very much for your kind attention.