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New Trends in Biotechnology
Martina Newell-McGloughlin
Director, University of California Systemwide
Biotechnology Research and Education Program
(UCBREP)
Paper: Nutritional and Safety Assessments of Foods and Feeds
Nutritionally Improved through Biotechnology:
http://www3.interscience.wiley.com/journal/119423779/issue
Newell McGloughlin, Plant Physiology, July 2008
http://www.plantphysiol.org/cgi/content/full/147/3/939
• High yielding affordable high quality food feed and fuel with minimum inputs
• 17% of land under cultivation degraded by human activity 1945 to 1990. Ag land shrinks by 20,000 ha yearly. (World Bank)
• Without yield increase land use will 2X by 2050.
• Latin America: greatest yield increase had lower land use (less deforestation)
• High yield “land sparing” better than “wildlife”-friendly inefficient land use farming
(Green, Royal Soc. Bird Protection 2005)
• EU pursuing 19th C technology, young scientists will flee. If the EU engages rational harmonized regulatory framework it will encourage a more rapid international diffusion of the technology.
• EU Commission "need to take urgent action to avoid negative implications for EU livestock production and agriculture overall".
1997 acreage
Reality check
Agriculture: A history of
Technology
8,000 BC
19thC
Ea 20th C
Md 20th C
1930s
1940s
1950s
1970s
1980
1990s
2000s
21st C
Cultivation
Selective Cross breeding
Cell culture
Somaclonal variation
Embryo rescue
Mutagenesis and selection
Anther culture
Recombinant DNA
Marker assisted selection
---omics - Bioinformatics
Epigenetics/RNAi/Paramutation
Adaptive technology/transgenomics
Systems Biology
Quality Traits - ($210B by 2015)
Improved post harvest characteristics
Shelf life, processing, taste
Improved Nutrition –Improved Functionality
Macro: protein, oils, carbs, fibre
Micro: Vitamins, minerals,
Phytochemicals – Antioxidants
Remove Antinutrients/allergens/ Toxins
CO2
Opportunities/Challenges for Biotech Crops
Agronomic Traits – $30B Biotic-
pest/disease/weeds/ Abiotic Stress:
Drought salinity marginal soils,
Yield
Value
Renewable Resources
Biomass conversion,
feedstocks, biofuels,
Phytoremediation
Concerns land/ water
use Perennials: Trees
Plants as Factories
Pharmaceuticals/ Industrial products
(Ventria – Rice Lactoferin Lysozyme
30% Diarrhea, recovery 3/6 days,
Concerns gene flow co-mingling
Source: ISAAA
• 2009, 14 M farmers 134 M hac (330 M acres) of biotech crops in 25 countries,
• 13.3 M farmers/125 M hacs (7%) in 2008. 13 /14 M (90 %) resource-poor LDC.
• 46% global age of biotech crops LDC- Total 57 countries have reg approvals.
• 6 EU planted 94,750 hacs in 2009, down from 7 and 107,719 hacs 2008, Germany
discontinued. Spain planted 80 % Bt maize maintained record adoption 22%.
• $44 billion 1996 to 2007, 44% yield gains, 56% reduction costs (including 359,000 tonne a.i. in pesticides); gains of 141 million tons, would require 43 M additional hectares
• Environmental pesticide footprint down by 15.4 %. GM reduction in 286 million kg of CO2 emissions equivalent to removing 6 M cars from the roads (Barfoot and Brookes 2008)
• Additional soil carbon sequestered since 1996 has been equivalent to 63,859 million tonnes of CO2 that has not been released into the global atmosphere.
• In 1994-95 farmers spent $78 Ha in herbicides; today they spend $37/Ha and insecticide use has decrease 90%.
• HT- increase in no- till: reduction in erosion, soils much healthier, organic matter, less soil compaction, better H2O usage, fuel use down by 20 gals/acre (Fawcett & Towery 2005 )
Environmental Impact
• China: Bt rice has the potential to increase yields up to 8 percent, decrease pesticide use by 80 percent (17 kg/ha) and generate US$4 billion in benefits annually (James, 2010). Significant decrease in adverse health effects – Lives saved
• Organisms in “Bt crops” fields fared better in trials than those with insecticides Monarch butterflies increase (Marvier, 2007)
• BT corn 90% reduction in mycotoxin fungal fumonisins -total US benefit estimated at $23m annually. (Wu, 2006)
• Origin Agritech China also approved Phytase maize (2009)
• CP papaya saved Hawaii papaya industry (and helped organic farmers!) may be the outcome for plum pox –C5 PTGS insurance against typhoid Mary in nurseries
• Blight-resistant potato (BASF -Rpi-blb1 and Rpi-blb2 NBS-LRR) -UI study concluded for the major potato-producing regions of the world would be $4.3 billion.
• ISAAA expects the number of biotech farmers globally to reach 20 million or more in 40 countries on 200 million hectares in just more than five years in 2015.
Two Down One doing Well
Spain: farmer Jose Victor Nogues” Most people can appreciate the huge benefits and lack of negative effects -Introducing GM maize was definitely the way forward
• France: Thierry de l'Escaille, European Landowners' Organization, - “wide-scale adoption of these three biotech crops in Europe could significantly increase annual production, improve farmer income by more than 1 billion Euros and reduce spraying. With results like these, it's easy to understand why farmers want access to this technology," said l'Escaille
• Sarkozy dit “mais non”!
Bt corn farmers earn about $85
more per acre, ISAAA (2007), while at
the same time producing a healthier
feed that is better for the environment.
Romania: Buzdugan farmers reported
price premiums of up to 10 percent for
biotech soybeans due to fewer weed
impurities. Average price gain 2%.
Production gain 29-33.5K M tonnes
(16-19% ) Earnings increase 35
million and 62.4 million euros (2004).
I can tell you that soybean farmers in
Romania are very interested in biotech
seeds," “Although the seeds are 10 to
15 percent more expensive, the income
gains make the extra cost more than
worthwhile” Now EU so no GM Soy!
• Other key highlights approval of SmartStax, a novel biotech
maize 8 different genes for insect and herbicide resistance
• SmartStax protects crops from major corn pests, including
European and southwestern corn borer, northern and
western corn rootworm, western bean cutworm, black
cutworm, corn earworm, and fall armyworm. SmartStax
will also provide resistance to glyphosate and glufosinate
herbicides. Dow AgroSciences field research trials
conducted in 2007-2008 confirmed SmartStax provides a
broader spectrum of insect protection in corn hybrids.
.
Genuity™ SmartStax™ Corn technology
-- Above-ground insect control: Dow's Herculex® I
technology with Monsanto's second-generation, two-gene
lepidopteran control technology called YieldGard® VT
PRO, SmartStax will provide protection against European
corn borer, southwestern corn borer, corn earworm, fall
armyworm, western bean cutworm, and black cutworm;
-- Below-ground insect control: Combining Dow
AgroSciences' Herculex® RW technology and Monsanto's
YieldGard VT Rootworm/RR2 technology, SmartStax will
provide protection against Western, Northern and Mexican
corn rootworms; and,
-- Weed control: Monsanto's Roundup Ready® 2 technology
with Liberty Link® herbicide tolerance, SmartStax will
offer broad spectrum weed and grass control with the
option of two different modes-of-action.
- asked the EPA to consider reduced refuge requirement due
to different modes of action - broader spectrum of control
and lessened likelihood of target pests developing resistance
Genuity™ SmartStax™ Corn technology
• Cross licensing Monsanto Syngenta
• Four years of field trials across six U.S. states showed 7 to
11% higher yields, compared to the first generation of
Roundup Ready soybeans.
• “Roundup Ready 2 Yield did very well for me last season,”
Jeff Barth, a farmer from Illinois, said. “They were planted
late and still performed five to six bushels better than the
first-generation Roundup Ready soybeans that were planted
earlier. I’m anticipating similar results this year, and that’s
why I will dedicate all of my 1,100 soybean acres to the
product when they become available.” This is also Barth’s
second year growing Roundup Ready 2 Yield soybeans.
Roundup Ready 2 Yield
Roundup Ready 2 Yield soybeans – the first product
of a new class of technology that allows more
efficient, precise gene insertion to directly impact
yields.
“Resistance” Genes natural and otherwise
• Rootknot nematodes R in tomato (Mi) and
(aphids). Alternate to fumigation (Williamson
UC Davis)
• Xa21 rice R gene confers resistance to several
Xoo. Defense response triggered by Xo
molecule, AvrXa21. Transgenic more resistant
due to copy number (Ronald)
• Use of apoptosis inhibition to protect plants
from mycotoxin damage (Gilchrist, UC Davis)
• Sclerotinia-resist sunflower oxalate oxidase
Pioneer wheat
• Zinc Fingers Dow/Sangamo
Abiotic Stress:
Drought, Cold, Heat, Salinity
Abiotic stress limiting factor for
crops reaching genetic potential
Improved water
conservation –
Fewer crop losses –
Higher yields on all
acres through
improved water
utilization –
Expand in drylands
BASF Drought-
tolerant corn 12
bushels more an acre
+ Gene EControl+ Gene DControl
Abiotic Stress:
Drought, ColdHeat, Salinity
Drought Stressed Rice
Abiotic stress limiting factor for crops
reaching genetic potential
Improved water conservation -Fewer crop
losses -Higher yields on all acres through
improved water utilization -Expand in
drylands - Nuclear Factor Y B subunit
Crops limited by salinity on 40 % world's
irrigated land (25 % US)
Cold: Engineering with COR15a Tf, role
in freezing tolerance.
Plants engineered with Choline oxidase
(codA) soil tolerated saline and cold
Homeodomain-leucine zipper (HD-Zip)
transcription factors respond to H2O &
osmotic stress, exongenous abscisic acid
Transport protein. Grow and fruit even in
irrigation water that is > 50X saltier than
normal. > 1/3 salty as seawater.
Blumwald and Zhang)
Abiotic stress limiting factor for crops reaching genetic
potential
Drought Tolerant Oilseed Rape The plant is engineered to
reduce the levels PARP [poly(ADP-ribose) polymerase], a key
stress-related protein in plants. This results in a crop which
was far better able to survive drought than reference plants.
Show relative yield increases of up to +44% compared to non-
drought tolerant varieties.
Bayer CropScience is currently conducting research work on
maize, cotton, oilseed rape and rice, with the objective of
developing a new generation of stress-tolerant, high-
performance crop varieties. The drought tolerant varieties have
a mutation that changes the activity of farnesyltransferase.
Pioneer Hi-Bred International is developing hybrids and
varieties that use water sources more efficiently and therefore
perform better during water deficits.
Maintaining yields during water stress will help preserve
grower incomes and yield more grain for the food and energy
value chain as well as reducing the need for irrigation.
- Improve Nitrogen Assimilation- Increase Sucrose hydrolysis,
Starch biosynthesis- Increase O2 availability - Modify photosynthesis
Yield Gene Control
Increased Yields
Forage Crops: This short-day
sorghum plant was used to map
the Ma-1 gene (genes which
modify photoperiodic behavior
and thus maturity). This gene
which works in other cereals
would offer particular benefits to
biomass and forage crops in
which flowering is undesirable
Nitrogen Use
Efficiency (NUE)
• Nitrogen fertilizer accounts for one-third of
the GHGs produced by agriculture
• Nitrous oxide 300 times more global
warming potential than carbon dioxide.
• Farmers spend $60 billion annually for 150
million tons of fertilizer (Stern Review 2006).
• Arcadia's Nitrogen Use Efficiency (NUE)
plants with equivalent yields that to
conventional varieties but which require
significantly less nitrogen fertilizer because
they use it more efficiently
• This technology has the potential to reduce
the amount of nitrogen fertilizer that is lost
by farmers every year due to leaching into
the air, soil and waterways. In addition to
environmental pressures, nitrogen costs can
represent a significant portion of a farmer's
input costs and can significantly impact
farmer profitability.
• licensed its technology to DuPont for use in
corn and to Monsanto for canola.
30% less applied N fertiliser
BioFuels
• LDC 30 % global energy. Growth driven by population and economic . Of
the world's 47 poorest countries, 38 are net oil importers, and 25 import all
of their oil, consuming much of their national income to pay for it.
• The challenge: 5-10 times more efficient - 2001 $5/gal -2005 18c/gal
• Biomass Conversion: Organic polymeric material, lignin, starches celluloses
bioconverted ethanol; hemicellulose hydrolyzed to sugars, xylose , glucose .
• Modify Plants and algae to improve enzymatic conversion.
• Modify enzymes to improve conversion and fermentation
• Maize other cereals, Switch grass, elephant grass poplars
• Biodiesel is biodegradable and non-toxic - alkyl esters made from the
transesterification of vegetable oils or animal fats., (60% less CO2)
• Rapeseed, Botryococcus braunii (Bb) colloidal microalgae
• Concerns: Food trade off – Efficiency of production – ecological impact
Many common food crops not perfect for nutritional
requirements of humans or animals.
Proteins: Maize, wheat, Sweet potato and cassava
WHO: 800 million people suffer from malnutrition, Protein-
energy malnutrition (PEM), the most lethal form, affects
1 in 4 children:
70% live in Asia, 26% Africa, 4% Latin America, Caribbean
• Grains low in Lysine – LDCs food - Feed Rations/pollution
• High Lysine maize: Use non feedback- enzyme (5X ppm)
• N assimilation modified pathway GDH 12% increase protein
• SRP Nonallergenic Amaranthus Albumin for potato
• High Protein: Cytokinin rescue flower pair kernels fused
single kernel two embryos - high protein/oil low CHO
• NAC Tfs (NAM) senescence and nutrient remobilization
leaves to grains, RNAi delay senes 30% protein, Zn, Fe
• Artificial Proteins:
• ASP-1-sweet potato 67% increase protein (EAA 80%)
Improved Nutritional Content
Improved Nutritional ContentCarbohydrates
• Starch High Amylose (resistant starch) inhibit 2 SBE
• Sorbitol role in fruit carbon metabolism and affects
quality attributes sugar-acid balance and starch accum
• Wheat puroindoline genes in rice better starch/flour
Fibre – Humans increase
• Polymers, Inulins, Fructo-oligosaccharides (FOS)
• SC Fructans sucrose taste: GI Tract health- fermented
colonic – bifidobacteria (compete pathogenic bacteria)
SC Fatty acid – anticancer/ inhibit HMG-CoAR less LDL
• SC fructans 1-SST Jerusalem artichoke. 90% sucrose
converted "fructan beets“ (Koops, 2000)
• Potato synthesize the full spectrum of inulins from
globe artichoke roots
• Lignans: enterodiol/lactone estrogen-dependent cancer
Forage Crops Fibre – Animals Decrease
• Brown midrib (COMT)–Decreased lignin increase
digestibility better feed conversion, livestock prefer
(Sorghum)
Improved Nutritional Content
Oils and Fatty acids
• Altering chain length and saturation level•
• Novel genes to produce unusual fatty acids in oilseed
• MUFA: High Oleic Acid: more stable than PUFA heat/
oxidation resistant, little or no postrefining
(hydrogenation): AS oleate desaturase soybean gave
>80% oleic acid (23%), Less SF milk/meat of animals
• MCT: medical foods, ergogenic aids. Acyl-ACPT
canola, increase in capric (C10) and caprylic (C8)
• High-CLA: Antiox- free radicals heart disease/cancer
• Omega -3 DHA-EPA “Fish Oil” CV/thrombosis/
Cancer/ Arthritis/ Cognitive/Mental/ premies -
D6 Desaturase: Canola/soybean precursor SDA 3.6X
ALA in generating EPA
• GLA safflower oil (C18:3n-6) anti-inflammatory effect,
improved skin health and maintaining weight loss
• Sitostanol: phytosterol phospholipid Block
cholesterol
Improved Nutritional Content
Micro nutrients Vitamins/ minerals:
• Vit A Golden rice II b-carotene-Rice 25X (CBP)
• Biofortified cassva flour- Field trial Nigeria (Sayre)
• Vit B Folate increase in rice (pregnancy deficinicies)
• Vit E a-tocopherol g-TMT; Vit C increase corn DHAR
Minerals: Ferritin (bean S protein), Metallothionein (Rice,
wheat). Ca/proton antiporter (sCAX) Ca transport into
vacuoles. Ca-fortified carrots enhanced absorption.
Multi vitamin Corn• Combinatorial direct DNA transformation rapid
production of multi-complex metabolic pathways
• transferred 5 constructs controlled by different
endosperm-specific promoters into white maize.
Different enzyme combinations show distinct metabolic
phenotypes – resulting in
• 169X beta carotene (60 mg/g v. 14 by breeding)
• 6X vitamin C, and
• 2X folate (Christou, 2009)
(bacteria)
(daffodil)
(daffodil)
Introduced
enzyme
(maize)
Improved Nutritional Content
Functional components - effects greater than nutrient value
alone
Phytochemicals:
• Carotenoids: Golden Rice, Sweet Potato - (sight,
development)
• Lycopene: polyamine Tomato – (reduce LDL, cancer)
• Isoflavones: genistein and daidzein, tyrosine kinase inhibitor
• Phenolics: resveratrol antioxidant Sirtuins (anti-aging)
• Flavanols: Catechins, Flavones: quercetin (less adjuncts)
Anti-nutrients: Trypsin Inhibitors; oxalic acid; furans;
Phytate, Bioavailability Phosphate, divalent ions: Phytase
(Rice, alfalfa)
Allergens: soy P34 removal; peanut; gluten digestion
Toxins: Glycoalkaloid (potato) AS solanine
• Cyanogenic glucoside (cassava) hydroxynitril lyase
• Concerns:
• High levels, Novel proteins, metabolites (pleiotropic effects)
Increased susceptibility to pathogens
Risk Management
Antibiotic Resistance (perceived not scientific)Transposon taggingPositive selection – exclusive energy source
Gene Flow-SpaceMale sterility“Terminator” technologyChloroplast transformation
Lack of specificity – pleiotropic effects (expected, unexpected)Site-specific recombinationCre-Lox
Effect on non-target speciesTissue specific expressionChloroplast transformation
Loss of effectiveness – resistance managementRefugiaGene Stacking, Gene Pyramiding, Gene shuffling
Reduced diversityMore sources of genetic diversity – rescue heritage varieties and
landraces Novel animals – Food safety, feral potential
Physical and Biological containment
Cooperation works
No
yellow
kernels
Organic Blue Cornfield near yellow non-organic field Fred Yoder Ohio
No cross
pollination
(no blue
kernels)
Biotech Corn Organic Corn
• Historically, worldwide the market adequately addressed
economic liability issues relating to trace presence of
unwanted material in any agricultural crop.
• US organics cannot be (legally) downgraded or growers
decertified by unintentional presence when all required
measures and best practices are adhered to and no
producer has been so impacted to date
Primum non nocere• Commercialization: 7 to 10 years -at least 9 review stages
• Biotech crops and foods more thoroughly tested than
conventional varieties ( “assumed” to be safe)- One
biotech soybean subjected to 1,800 separate analyses
• 23 feeding studies - dairy, beef, poultry, soy/corn
equivalent in composition, digestibility and feeding value
to non-GM. Clarke et al 2000
• Substantial equivalence with parent - Molecular
characterization (17) Toxicity studies (5) - marker genes
(4) - Nutritional content (7+)- Allergenicity potential -
Anti-nutritional effects - Protein digestibility
• Environmental aspects (5 items)- Ecological impact (5
items) OECD, CBD, CODEX
Omic studies
Wheat ( Baker 2006), Potato (Catchpole 2005)
Transcriptomic and Metabolomic studies show greater variation between
conventional bred cultivars and even growth locations than between GM and
parental variety (except of course for the intended modification!) - differences
between sites were generally greater than differences between lines
Greatest Challenges going forward
• Technical
• Intellectual Property: PIPRA - Specialty crops – FTO
• Liability
• Biosafety: so–called – LDCs – Specialty crops
• Acceptance: - countering fear and misinformation
(ethical) - moral imperative real need v. hypothetical risk
I hope that there is nothing
genetically modified in this