26: Biotech

Genetic Modification ('GM')

  • Technologies
  • Impacts
  • Gene editing

Basic Anatomy Knowledge

  • Weinman et al (2009) surveyed 722 people in London to assess their knowledge of basic anatomy.
  • Results:
    • Heart: 47% Correct, 54% Incorrect
    • Lungs: 31% Correct, 69% Incorrect
    • Stomach: 38% Correct, 62% Incorrect
    • Intestines: 86% Correct, 14% Incorrect
    • Bladder: 81% Correct, 19% Incorrect
    • Thyroid: 42% Correct, 58% Incorrect
    • Liver: 53% Correct, 47% Incorrect
    • Kidneys: 43% Correct, 58% Incorrect

Global Public Knowledge of Biology

  • United States (2010) (n = 1,932), EU (2005) (n = 16,029), Russia (2003) (n = 2,107)
    • "Ordinary tomatoes do not contain genes, while genetically modified tomatoes do"
      • US: 47% Correct, 53% Incorrect
      • EU: 41% Correct, 59% Incorrect
      • Russia: 22% Correct, 78% Incorrect
    • "Antibiotics kill viruses as well as bacteria"
      • US: 50% Correct, 50% Incorrect
      • EU: 46% Correct, 54% Incorrect
      • Russia: 18% Correct, 82% Incorrect

Achievements of Conventional Plant Breeding

  • Yield increases typically 3-fold in this century via:
    • Increased harvest index
    • Increased length of growing cycle
    • Reliability
    • Resistance to abiotic and biotic stress
    • Increased range of cultivation
  • Will NOT be replaced by GM or gene editing

Terminology

  • Many names for the same principle:
    • Genetically Modified (GM)
    • Genetically Manipulated (GM)
    • Genetically Modified Organism (GMO)
    • Living modified organism (LMO)
    • Genetically Engineered (GE)
    • Transgenic, etc.
  • GMOs are officially defined in the EU legislation as:
    • "organisms in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating and/or recombination."

Pesticide Chemicals

  • Control weeds, insects, fungi
  • Post-war era of synthetic pesticides
  • Research institute in Hertfordshire: field experiment on wheat yields since 1856

Global Crop Yield vs Pesticide Use

  • Lines: Global average crop yield per area 1960-2004
  • Bars: Global pesticide use ­15-20×
  • Herbicides ('weedkillers'): biggest market

Effectiveness of Pest Controls

  • Global average effectiveness of pest controls for 11 crops
  • Weed controls relatively effective

Herbicides

  • Different cellular targets
  • Finale 150 - contains glufosinate, an irreversible glutamine synthetase inhibitor produced by certain Streptomyces bacteria.
  • Auxin herbicides disrupt cell growth in dicot weeds but grass less sensitive.

Glyphosate

  • Inhibits ‘EPSP’* synthase of ‘shikimate pathway’
  • EPSP needed for biosynthesis of aromatic amino acids, flavonoids, lignin, auxin
  • Roundup® active component: ‘glyphosate’
  • Glycine phosphonate. *5-enol-pyruvyl-shikimate-3-phosphate

Discovery of Glyphosate-Resistant EPSP Synthase

  • Glyphosate-resistant bacterial strain ‘CP4’ isolated from glyphosate production waste
  • CP4 EPSP synthase: Gly→Ala mutation at active site allows normal reaction but glyphosate does not interfere
  • Genetically modify crop plants with CP4 EPSP synthase gene → glyphosate-resistant crops

Requirements for Making GM Crops

  • Defined gene sequences of known function
  • Or synthesised artificially (synthetic biology)
  • Effective vectors including promoters, targeting sequences, terminators and selectable markers
  • Effective transformation systems.

Common Methods for Creating GM Crops

  • Agrobacterium method
    • Soil bacterium Agrobacterium tumefaciens is the causal agent of crown gall disease
    • A. tumefaciens infects the plant through its Ti plasmid. The Ti plasmid integrates a segment of its DNA, known as T-DNA, into the chromosomal DNA of its host plant cells
  • Particle gun method
    • Gene gun or a biolistic particle delivery system, is a device for injecting cells with DNA. The payload is an elemental particle of a heavy metal coated with plasmid DNA.

Roundup-Ready Crops

  • 1996: Monsanto develop 'Roundup-Ready®' soybean, maize, cotton
  • By 10 years later, almost all soybean in USA was Roundup- Ready
  • 'Roundup-Ready' crops sprayed with glyphosate to keep clear of weeds

Glyphosate Use and Glyphosate-Resistant Weeds

  • 1995-2014: ­9× in agricultural glyphosate use in US (­15× globally)
  • Since 1974, 8.6 billion kg of glyphosate have been applied globally
  • 16 glyphosate-resistant weed species in Roundup-Ready® cropping systems
  • One resistance mechanism is over-production of EPSP synthase
  • Bollgard II® XtendFlex® is the first triple stack herbicide-tolerance technology in cotton, with tolerance to dicamba, glyphosate and glufosinate herbicides.

Bt Cotton

  • Cotton bollworm Helicoverpa armigera caterpillar on cotton
  • ‘Cotton bollworm’ moth: worst single insect pest costing >$5 billion annually
  • ‘Bt’ toxin gene (cloned from bacteria) in Monsanto’s ‘Bollgard II’ GM cotton
  • Used as organic pesticide
  • ≈80% global cotton GM

Mechanism of Bt Toxin

  • "Cry" genes produce d-endotoxin crystals are solubilised in midgut and activated by proteolysis
  • Only functional part of gene used
  • Optimised for plant expression
  • Plants produce endotoxin
  • Only feeding insects killed

Traits in Engineered Crops

  • >30 traits currently engineered for commercial use
  • Most popular are herbicide tolerance, insect resistance and both together
  • Many other examples, e.g., papaya ringspot virus resistance or anthocyanin-rich biotech pink pineapple

Global Distribution of GM Crops (2018)

  • In 2018, global area of biotech crops was 191.7 million hectares, representing an increase of 1.1% from 2017, equivalent to 1.9 million hectares.
  • Top countries growing GM crops:
    • USA: 75.0 million hectares
    • Brazil: 51.3 million hectares
    • Argentina: 23.9 million hectares
    • Canada: 12.7 million hectares
    • India: 11.6 million hectares

Adoption of Biotech Crops in Brazil

  • Corn, winter
  • Corn, summer
  • Corn, total
  • Soybean
  • Cotton

Positive Impacts of GM Crops

  • Yield: 21.6% increase
  • Pesticide quantity: -36.9% decrease
  • Pesticide cost: -39.2% decrease
  • Total production cost: 3.3% increase
  • Farmer profit: 68.2% increase

Papaya Ringspot Virus (PRSV) in Hawaii

  • 1992-1997
  • Virus spread by aphids kills trees
  • Production halved by end decade

Mechanism of Virus Resistance in GM Papaya

  • A gene from a virus, such as the papaya ringspot virus is engineered in the crop and is expressed forming segments of double-stranded (ds) RNA.
  • The dsRNAs trigger the plant's defense mechanism and are cleaved into short RNA molecules.
  • The short RNA molecules are complementary to the RNA from the virus. Again, these trigger the plant's defense mechanism and prevent the virus from replicating.

Transgenic Papaya and Controversy in Thailand

  • 'Rainbow': GM papayas
  • Now 85% of Hawaiian papaya crop
  • Cornell University transferred virus resistance gene into Thai varieties of papaya
  • 2004 field trials established in Thailand.
  • Local farmers ‘stole’ the fruit from the research stations
  • Greenpeace launches a campaign against the GM plants
  • Thai government destroys all the plants

Genome Editing

  • Definition: techniques for genome engineering that involve DNA repair mechanisms and/or replication for incorporating site-specific modification into a genomic DNA.
  • Genome engineering = process of introducing intentional changes into genomic DNA (ISO/DIS 5058-1).
  • Meganucleases (MN)
  • Zinc-finger nucleases (ZFN)
  • Transcription activator-like effector nucleases (TALEN)
  • Clustered regularly interspaced short palindromic repeats (CRISPR) coupled with a CRISPR-associated protein (Cas)
  • Oligonucleotide-directed mutagenesis (ODM)
  • Site-directed mutagenesis technique but does not use a targeted exonuclease

Timeline of Genome Editing Advancements

  • CRISPR/Cas system initially discovered E. coli genome in 1987, adapted system used to edited human and mouse cells in 2013
  • First GE humans born in China in October 2018 – twins Lulu and Nana (researcher fined and imprisoned)
  • First GE crop grown in USA in 2019
    • Cibus’ ultra-high-oleic oil canola
  • GE organism still classed as a GMO in EU, but not England

UK Legislation on Precision Bred Organisms

  • "Precision bred organism” means a precision bred plant or a precision bred animal.
  • An organism is "precision bred” if: every feature of its genome could have resulted from: traditional processes, whether or not in conjunction with selection techniques, or its genome does not contain any feature that results from the application of any artificial modification technique other than modern biotechnology.

GABA-Enriched Tomato

  • First CRISPR-edited food to enter market
  • Increased the amount of GABA in tomato
  • GABA (gamma-aminobutyric acid) is a neurotransmitter, a chemical messenger produced by the brain and nervous system.
  • Sanatech do not to claim that its tomatoes therapeutically lower blood pressure and promote relaxation.
  • Do advertise that consuming GABA, generally, can achieve these effects and that its tomatoes contain high levels of GABA.

High Vitamin D Tomato

  • Daily intake of vitamin D in adults in the UK is 7.2μg7.2 \mu g, below the RDA of 10μg10 \mu g
  • Researchers at the John Innes Centre (JIC) discovered that removing one gene encoding for the SL7-DR2 enzyme boosts vitamin D levels
  • Full RDA of an adult being obtained by the consumption of two small edited tomatoes
  • In the UK the Food Standards Agency approve new PBOs

Summary

  • ‘GM’ plants altered in a way that does not occur naturally by mating and/or recombination
  • Major GM crops exploit pesticide technologies but diverse GM products appearing
  • Gene edited crops have reached market and soon to land in the UK