Adoption of industrial biotechnology:

The impact of regulationGeorge T. Tzotzos, Ph.D

United Nations Industrial Development Organization

Adoption of Ag-biotech

Present status & influencing factors

Global GM crop plantings by crop 1996-2004

Source: Graham Brookes & Peter Barfoot PG Economics Ltd, UK, 2004

GM crops: the global socio-economic and environmental impact – the first nine years 1996-2004

Source: Graham Brookes & Peter Barfoot PG Economics Ltd, UK, 2004

GM crops: the global socio-economic and environmental impact – the first nine years 1996-2004

2004’s share of GM crops in global plantings of key crops

Costs of new GM products

Regulatory costs & IP acquisition drive industry

consolidation

Source: Inverzon International Inc. (St Louis, US), in Papanikolaw, 1999 Notes: AgrEvo and Rhone-Poulenc are merging into Aventis. AgrEvo figures include seed

activities. Rank depends on average exchange rates used.

Biotech & the developing world

Pressing problems need urgent solutions

The problem:land and & population

0

2

4

6

8

10

1950 1990 2025

S1 0

0.1

0.2

0.3

0.4

0.5

1950 1970 1990 2050

S1

World populationArable land per inhabitant (ha)

Abiotic stress: extent of the problem

Fact

Drought 5000 lt H2O for 1kg of rice grain. 70% of world’s H2O used in agriculture

Salinity 380 mil ha affected by high salinity

Acidity 40% of world’s arrable land affected. In S. America only, 380 mil ha affected

Temperature 70% of the total land in the Andes is devoted to potato production prone to cold stress

Only some 10% of the world’s 13 billion ha is farmed. Alongside losses due to pests and diseases, a further 70% of yield potential has been calculated to be lost to abiotic stress

Source: CGIAR/FAO, 2003. Interim Science Secretariat. Applications of Molecular Biology and Genomics to Genetic Enhancement of Crop Tolerance

to Abiotic Stress

Potential biotech solutions

Genetic improvement of orphan crops Tolerance to abiotic stresses Vaccine producing crops Industrial crops for marginal lands Bio- & phytoremediation

Rationalising biotech regulation

Move focus away from the transgenic process

Rationalise the basis of transgenic regulation

Exempt selected transgenes from regulation

Create regulatory classes in proportion to potential risk

Revisit ‘event’ based regulation

Reasons for focusing away from the transgenic

process Focus on the phenotypes of transgenic plants and

their safety & behaviour in the environment

Environmental and toxicological issues are influenced by the expressed traits rather than the gene per se

Although conventional breeding uses complex genomic manipulations (mutagenesis; somaclonal variation; protoplast fusion; embryo rescue; ploidy manipulations) its products are seldom characterised at the molecular level before variety release because regulation is based on long history of safe & beneficial use. For example mutation-derived herbicide resistance is deregulated

Reasons for rationalising the basis of transgenic regulation

Regulation triggered by constructs derived from pathogens (e.g. Agrobacterium, CmV promoter,

etc.)

•Agrobacterium transfers naturally to plant genomes and at times becomes stably integrated into the plant genome (e.g. A. rhizogenes

in tobacco).

• Viruses are ubiquitous in crop-derived foods. 14-25% of oilseed rape in the UK is infected by CmV and similar numbers have been estimated for cauliflower and cabbage. Historically humans have

been consuming CmV and its 35S promoter in much larger quantities than in uninfected transgenic plants

Exempting selected transgene & classes from

regulationGeneral gene suppression methods (e.g. antisense, sense suppression, RNAi)

Non-toxic proteins that are commonly used to modify development

Use of selected antibiotic resistance marker genes

Selected marker genes that impart reporter phenotypes

Creating regulatory classes in proportion to risk

Low

imparted traits are functionally equivalent to those manipulated in conventional breeding and where no novel protein or enzymic functions are imparted.

‘domesticating’ traits retarding spread into wild populations (e.g. sterility, ‘dwarfism’, seed retention, modified lignin) (bioconfinement)

Medium

Plant-made pharmaceutical/industrial proteins plants with novel products that have low human or environmental toxicity or that are grown in non-food crops and have low non-target ecological effects (e.g. plants used in remediation)

High

Where transgene products have a documented likelihood of causing harm to humans, animals or the environment (e.g. bioaccumulators of heavy metals are likely to have adverse effects on herbivores)

Revisit ‘event’ based regulation

The regulatory premise

The actual “genomic” situation

Transgenic eventEvent = successful transformation

Events differ in the specific genetic components and in the place of insertion of the foreign DNA into the host

chromosome

Maize has 10 chromosomes any of which might incorporate the transgene

‘Event’ based regulation. The regulatory premise

insertion sites of transgenes cannot be currently targeted (random insertion). Some insertions may alter the expression or inactivate endogenous genes resulting in unexpected consequences

uncertainties significantly exceed those arising in conventional breeding (introgression or mutagenesis)

‘Event’ based regulation. Genomic science says

otherwiseGenome mapping and sequencing results indicate that site-specific characterisation has little value in the regulatory context. Total DNA content, the number of genes, gene order can vary among varieties of the same species

Different varieties of maize, chilli pepper & soybean can differ by as much as 42%, 25% & 12% in DNA content respectively. For soybean this means varietal difference of 100 million base pairs or more.

Closely related species such as maize, rice & sorghum have genomic regions with differing arrangements of essentially the same set of genes. Small insertions and deletions in maize occur every 85 base pairs in non-coding regions and the frequency of SN Polymorphisms is 1 in 5 to 200 base pairs.

Transposons and retrotransposons continually insert themselves between gens and are likely to have resulted in improvements in plant adaptation.