Evolution of GM crop development – from the 1990s to today; … · 2015-07-09 · Biotech Products and Cultivation in Europe – Key Events . 1997 Bt 176 Approved for cultivation

Evolution, Pipeline and Future of Biotech- 2015 Page 1

ISTA meeting, Montevideo, 2015

Dr. Ray Shillito, Bayer CropScience, USA

• Evolution of GM crop development – from the 1990s to today;

• Future challenges: • Pipeline products; • Next generation GMOs and

impacts on seed testing

From the 1990s 1970’s to today;


Three key elements led to the first developments in Ag. Biotech

Agrobacterium tumefaciens Plant Tissue Culture Molecular Biology and Biochemistry


The Initial Development of Plant Biotechnology occurred in the 70’s and 80’s in both the EU and USA.


Critical Technologies

1869 - DNA discovered

1953

- Structure of DNA solved

1972 – Discovery of restriction enzymes – DNA cloning

1975 - Southern blotting

1976 – DNA Sequencing

1983 PCR invented Agrobacterium- transformation using disarmed vectors Transformation without Agrobacterium

1984 – Oligomer biosynthesis

1994 – Agro transformation of Monocots

1928 – demonstration of

bacterial transformation 1987 – Gene Gun

Moratorium – 1974 -75


Some of the Technologies with Direct Impact

Selectable markers Tissue culture Protoplasts/PEG/electroporation Agrobacterium tumefaciens Biolistics Whiskers Agrobacterium in monocots A188 (3 way sweet corn cross)

PCR Codon optimization Antisense / RNAi Bt proteins Cre/Lox etc.


Page 7

The view from 1996 was like this..

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


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case of Mad cow disease in Europe 1999 - Dioxin contamination (animal feed) scandal hits Belgium 1999 - Coke products withdrawn in Belgium due to bad CO2

2010 Amflora potato approved for cultivation

EU Moratorium on approvals – 1998 - 2004


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)




Global Area (Million Hectares) of Biotech Crops, 2014: by Country

Diversity of Biotech Products

Soybean 50%

Maize 30%

Cotton 14%

Canola 9%

Others 1%

Major Biotech Crops Maize Soybean Cotton Canola Other Biotech Crops Sugar beat Alfalfa Papaya Eggplant Squash Potato Melon Sugarcane Wheat

Clara Rubenstein, Pioneer, a DuPont Company

Global Adoption Rates (%) for Principal Biotech Crops (Million Hectares, Million Acres), 2014

Country Value (USD million) Country Value (USD

million)USA 12,000 Morocco 140China 9,950 Switzerland 140France 2,800 Bulgaria 120Brazil 2,625 Chile 120Canada 2,120 Nigeria 120India 2,000 Serbia 120Japan 1,350 Slovakia 110Germany 1,170 New Zealand 100Argentina 990 Uruguay 96Italy 767 Ireland 80Turkey 750 Paraguay 80Spain 660 Portugal 80Netherlands 590 Algeria 70Russian Federation 500 Kenya 60United Kingdom 450 Iran 55South Africa 428 Israel 50Australia 400 Tunisia 45Republic of Korea 400 Bolivia 40Mexico 350 Colombia 40Czech Republic 305 Slovenia 40Hungary 300 Peru 30China, Taiwan 300 Zimbabwe 30Poland 280 Malawi 26Sweden 250 Libya 25Romania 220 Saudi Arabia 20Denmark 218 Zambia 20Greece 200 Philippines 18Belgium 185 Ecuador 15Finland 160 Tanzania 15Austria 145 Uganda 10Egypt 140 Dominican Republic 7

The commercial world seed market is assessed at approx. USD 45 billionTotal USD 44,925 million (2013 figures)

Seed testing is important 6 of the top 10 commercial markets for seed are growing Biotech crops Data from: ISF 2014 ISAAA 2014


Pipeline Products


Challenges for Agri-Businesses

Research and innovation are the key to mastering the challenges of the New Ag Economy

Increase tolerance of plants to climatic variability à develop new varieties using state - of - the - art technologies à improve plant health and nutrient uptake

Safeguard and increase yields from constant land area à better resource management (targeted use of crop

protection, irrigation technology and fertilizers) 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

Limited arable land coupled with rising demand

Climate change


Industry investing in multiple modes of action, 1996-2020 (as of 2014)

CORN

SOYBEANS

COTTON

ü Commercial offering q Future or potential offering

WEED CONTROL ABOVE GROUND PESTS BELOW GROUND PESTS

ü Glufosinate-tolerance ü Glyphosate-tolerance ü Imidazolinone-tolerance ü 2,4-D tolerance q FOP tolerance

ü Caterpillar protection Gen1 ü Caterpillar protection Gen2 ü Caterpillar protection Gen3 q Caterpillar protection Gen4

ü Rootworm protection Gen1 ü Rootworm protection Gen2 ü Rootworm protection Gen3 q Rootworm protection Gen1

ü Glufosinate-tolerance ü Glyphosate-tolerance ü Sulfonylurea-tolerance q Dicamba tolerance q Glufosinate-tolerance Gen2 q HPPD tolerance q PPO tolerance

ü Caterpillar protection Gen1 ü Caterpillar protection Gen2 q Stink bug protection

q Soybean cyst nematode protection

ü Glufosinate-tolerance ü Glyphosate-tolerance q 2,4-D tolerance q Dicamba tolerance q HPPD tolerance

ü Bollworm protection Gen1 ü Bollworm protection Gen2 ü Bollworm protection Gen3 q Bollworm protection Gen4 q Lygus protection

ü Root knot nematode protection Gen1

q Reniform nematode protection

q Root knot nematode protection Gen2








There are a lot of Events/Products!

Source: JRC Report, 2009 / ISAAA

Crop Commercial Events in 2008

JRC Projected Commercial Events in 2015

Possible Commercial products in 2014

Approved historically for cultivation (inc stacks)

Approved historically for food (inc stacks)

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 Crops

7 23 ~11 35 33

Flowers - - 22 22 0

Total 33 124 ~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


Next generation GMOs and impacts on seed testing


New events are now arising from sources other than major biotech providers

These come from small companies and/or government research. Products from major providers are registered in global markets

• Methods and reference materials are available Some other products are only registered in single countries or regionally and

• Methods and reference materials are not freely available

Could present a challenge for detection in seeds Screening may be carried out based on knowledge of genetic elements present in the events (literature and other sources)


There were two main sources of early promoters: CaMV, Ti plasmid


The Modern Toolbox is Multidimensional: Tool Benefits

DNA trait markers Can eliminate need for phenotyping of plants (MAB)

Individual seed /plant testing

Saves time/money/space/labor, increases breeding throughput

Robotics Speed increase by integration of workflows in analysis of markers

Expression of introduced genes

Biotech approach to add new genes (herbicide and insect tolerance)

“RNAi” Biotech approach to alter biochemical pathways through the alteration of native gene expression

TALENs/CRISPRs Emerging techniques for the specific editing of native genes.

Genome wide selection/ genotyping by sequence

Emerging technique enabled by cheap/fast DNA sequencing for the discovery of new markers for breeding, acceleration of backcrossing


Nucleases, TALENs and CRISPRs

Chen and Lin: Promises and issues of GM crops, Current Opinion in Plant Biol., 2013


Nucleases, TALENs and CRISPRs

Generate ds breaks at specific locations in DNA which are repaired, leading to mutation-like changes From a detection point of view: • The changes cannot be distinguished from mutations • There is a discussion on whether and how these products

might be considered regulated • In any case we may need detection methods for purity

testing


Detection of new GMO’s

• Most regulations were written and adopted during a significantly simpler technology landscape.

• Today’s reality may not have been anticipated. • Screening assays based upon genetic elements will become

less useful as new selectable markers, promoters and technologies are introduced.

• The costs and complexities to monitor seed purity will increase dramatically.

• Single event analysis remains methodology of choice • 4 – 6 component stacks will become commonplace • Increasing list of species as new technologies are adopted

Change is inevitable

The Future

• Use of Agricultural Biotechnology continues to expand • Many new events are being developed in multiple crops by both

traditional biotechnology providers and new sources • Events will originate from different global regions • Stacked events will be more common and complex • Products of newer technologies are a challenge to distinguish from

‘natural’ processes • Thus seed (GMOs) testing will become more complex and difficult

• It is important that global trade in seeds is not disrupted • Reasonable Low Level Presence thresholds will be important in

order to avoid trade disruptions

Documents

Evolution of GM crop development – from the 1990s to today; … · 2015-07-09 · Biotech Products and Cultivation in Europe – Key Events . 1997 Bt 176 Approved for cultivation