ASSOCIATE PARLIAMENTARY FOOD & HEALTH FORUM GM Crops and Food Security 2010-2050

Wednesday 21 July 2010House of Commons

Is GM technology simply an extension of traditional breeding methods for the

production of new varieties of crops and, if not, does it matter?

Michael Antoniou

King’s College London School of Medicine,

Guy’s Hospital, London

Central Tenets of Genetic Modification in Agriculture

The use of genetic modification (GM) inagriculture is a natural extension oftraditional breeding methods but moreprecise and safer.

Genes are isolated units of information that can function in a totally predictable manner even when moved between unrelated species using GM technology.

Substantial Equivalence and Generally Recognised as Safe

Only GM gene and its product are seen as source of riskGeneral biochemical analysis onlyAssessment of known toxins/allergens only

GM and non-GM parental plant are “substantially equivalent” ifthey contain similar amounts of biochemical components withinlimits of natural variation

No feeding trials required if they substantial equivalence is found (USA);only 90-day feeding test required in EU.

FLAWS: Only looks at gross biochemical composition; only looksat known components.

NOTE: BSE cow is “substantially equivalent” to a normal cow!

The New Genetics1. Gene order/organisation in DNA is very precise.

3. Genes exist in groups or families.

4. Genes work in groups; no gene works in isolation.5. Gene function is tightly regulated in a highly coordinated manner by both local and distant genetic elements and layers of epigenetic control.

6. Genes have co-evolved to function together as an integrated whole within a given organism. 7. Genes are now defined more by their context than by purely their information content.

2. In most cases, more than one RNA/protein is produced from a given gene. Many proteins perform more than one function.

8. Normal sexual reproduction or breeding can take place only between closely related organisms. Genes are inherited in their natural groupings that have been finely tuned to work harmoniously together by millions of years of evolution.

Genetic Modification : The FundamentalsNew technology: only ~28 years old.Does not involve natural sexual reproduction methods: GMOs are laboratory “creations”; e.g. genes inserted into plant cells under laboratory culture using mechanical (“biolistics”) or bacterial infection methods.

Allows transfer of one or few genes between totally unrelated organisms: e.g. bacterial, viral or animal genes into plants.Employs artificial combinations of genetic material: e.g. Cauliflower mosaic virus/petunia genetic switch control elements linked to a bacterial gene inserted into soya beans to confer herbicide resistance.The GM transformation process is very inefficient. Only a very low percentage of plant cells take up the foreign gene cassette; antibiotic resistance genes have to be used to select for transformants.

Generation of GM plants involves the random insertion or splicing of a foreign gene into the host DNA/genome. The GM transformation process as a whole is highly mutagenic, invariably to a lesser or greater degree always disrupting gene order and function.

GM in Plants

GM bears no resemblance to natural sexual reproduction and bypasses natural species barriers.

GM brings about novel combinations of genes that have not evolved to function together.

GM transformation process (transgene insertion plus tissue culture) is highly mutagenic.

GM to a lesser or greater degree, always disrupts host genetic order and function.

Consequences of GM TransformationCombined effects of GM (mutation effects; novel combinations of gene products) can disrupt genetic and protein biochemical function leading to the generation of novel toxic effects, allergies and altered nutritional value.

Introduces new substances with potential toxic effects from: transgene product, altered farming practice.

GM in agriculture possesses an unpredictable component that can frequently be greater than the intended change.

CONCLUSION: from basic science and technological perspective, GM is NOT a natural extension of traditional breeding and is NOT technically neutral.

GM Transformation Can Interfere with Crop Performance and Reduce Yields

Growth ProblemsCertain varieties of GM cotton suffered cotton ball and root development problems Certain varieties of GM cotton are more susceptible to nematode attack GM soya has a lower tolerance to heatGM soya has highly reduced uptake of manganese

No Increase in Yield PotentialGM soya beans have given consistently lower yields for more than a decade; “yield drag”*.Field trials show GM soya to have a 10% lower yield potential with 50% of the drop due to the genetic disruptive effect of the GM transformation processField trials of Bt insecticide producing maize hybrids showed that they took longer to reach maturity and produced up to 12% lower yields

*Note: RR2 Soya development

GM Transformation Can Interfere with Crop Performance and Reduce Yields

Report claims no yield advantage for Bt cropsNature Biotechnology, 27: 588-589, 2009.

Failure to Yield: Evaluating the Performance of Genetically Modified Crops (April 14, Union of Concerned Scientists, USA), argues that the adoption of expensive, GE-based approaches to agriculture has been at the cost of cheaper alternatives that carry less environmental risk

http://www.ucsusa.org/assets/documents/food_and_agriculture/failure-to-yield.pdf

Ideal GM Food Animal Feeding Studies

GM foods designed for life long consumption, therefore and animal feeding study evaluating safety should be:

Long-term; that is life longMultigenerationalEmploy at least three animal species including farm animals that will consume them Measure a broad range of physiological and biochemical parameters

Only valid as GM vs non-GM parental (“isogenic”) comparison

Note: OECD guidelines; 3 animals but ONLY for 90 days feeding!

Controlled Animal Feeding Studies Show Clear Signs of Toxicity linked with GM crops

Academic Based Studies

Potential Health Effects of GM Foods : Some Current Evidence for Unexpected Toxic and Allergenic Events

Extensive laboratory animal feeding studies with commercialised GM food raise worrying health concerns

•Liver, pancreas and testes function was disturbed in mice fed GM soya (Malatesta et al., 2002, 2003, Vecchio et al., 2004)•Mice fed GM soya over their entire life time (24 months) show more acute signs of ageing in their liver (Malatesta et al., 2008)

Old and young mice fed with GM insecticide producing maize showed a marked perturbation in immune system cell populations and in plasma cytokine profiles (Finamore et al., 2008)

Potential Health Effects of GM Foods : Some Current Evidence for Unexpected Toxic and Allergenic Events

Extensive laboratory animal feeding studies with commercialised GM food raise worrying health concerns

•Rats fed GM insecticide producing maize over three generations: Higher incidence in necrotic areas in liver and kidneys; alterations in blood biochemistry (Kılıc and Akay, 2008)

Feeding of GM insecticide producing maize to mice over 4 generations:Build up of abnormal structural changes in various organs (liver, spleen, pancreas)Major changes in the pattern of gene function in the gut - disturbances in the chemistry of this organ system (e.g. in cholesterol production, protein production and breakdown)Significantly reduced fertility(Velimirov et al., 2008)

Industry Studies

MON863 GM maize causes haematological disturbances and organ weight loss in rats

Only a 90-day feeding study comparing GM and non-GM equivalentdiets showed significant changes in their blood cells, livers andkidneys, which might indicate disease. Review of Some of the Significant Differences:

Measure Function Might indicate Comments

Increased Basophil Counts

Creates histamine Allergic reaction Other Bt corn studies suggest possible allergic reactions.

Increased Lymphocytes and white blood cells

Immune reactions to fight infections, etc.

Infections, various toxins and diseases

Researchers omitted tests to see if the spleen, which creates lymphocytes, was affected.

Decreased Reticulocytes

Becomes mature erythrocytes (red blood cells)

Anemia 5% variability is allowable. Astoundingly, Monsanto claimed a 52% decrease was “attributable to normal biological variability.”

Decreased Kidney Weight

To clear waste products

Blood pressure problems

Any inadequacy in kidney function is potentially life threatening.

IncreasedBlood Sugar

Essential energy source

  A 10% elevation cannot be written off as insignificant, given the diabetes epidemic.

 •Rats fed insecticide-producing GM maize grew more slowly, suffered problems with liver and kidney function, and showed higher levels of certain fats in their blood

Signs of Toxicity from Commercialised GM Maize Varieties

Flaws and Counterclaims Use of irrelevant control comparators

Use too few animals; not enough animal types

Wrong statistical analytical methods

Too short feeding trial time; only 90 day max at present required/conducted

Statistically significant but not biologically significant

Sex differential effects

Significance of Rodent GM Food Feeding Studies

Surrogates for human toxicological investigations

“Facts do not cease to exist because they are ignored”Aldous Huxley

Central Tenets of Genetic Modification in Agriculture

The use of genetic modification (GM) inagriculture is a natural extension oftraditional breeding methods but moreprecise and safer.

Genes are isolated units of information that can function in a totally predictable manner even when moved between unrelated species using GM technology.

Sources of Possible Toxic Effects of GM Foods

GM gene product: Enzymes responsible for herbicide toleranceBt toxin: immunogenic, adjuvant

Changes in farming practice: Broad spectrum herbicide residues

Adverse mutagenic effects of GM transformation:Novel toxins, allergens and disturbed nutritional value

Consequences of GM Mutagenic Effects Zolla L et al., Journal of Proteome Research, 7: 1850-1861, 2008.

Disturbance in GM MON 810 maize protein expression profile (“proteome”):

43 proteins up or down in level in GM vs controls which could be specificallyrelated to the transgene insertionGM plants responded differentially to the same environment compared totheir non-GM isogenic controls, as a result of the genome rearrangement derived from gene insertion

Newly expressed protein: zein, a well-known allergenic protein

Major concern, a number of seed storage proteins exhibited truncated forms having molecular masses significantly lower than the native ones

This and animal feeding studies invalidates the approval of MON810 for commercial use.

Is there a place for Biotechnology in

Agriculture?

Marker Assisted Selection - MASResponsible, More Effective and Safe Use of

Biotechnology in AgricultureThe New Genetics tells us that preservation of species barriers, natural gene order and function is vital to maintain integrity and safety

Use of more holistic (“systems biology”) aspects of modern biotechnology:

Marker Assisted Selection (MAS): a non-GM biotechnologyGuide and accelerate the traditional breeding processGenetically complex properties possible (e.g. enhanced nutrition, taste and yield potential, pest and blight resistance, and

tolerance to drought, heat, salinity and flooding).

Use of existing crop varieties and related wild relatives in traditional breeding programmes to develop varieties with enhanced characteristics useful in contemporary agriculture.

Marker Assisted Selection (MAS)

Novel upland rice variety bred using marker-assisted selection and client-oriented breeding released in

Jharkhand, India

Monday, May 4, 2009By Katherine Steele http://greenbio.checkbiotech.org/news/novel_upland_rice_variety_bred_using_marker_assisted_selection_and_client_oriented_br A novel upland rice variety, Birsa Vikas Dhan 111 (PY 84), has recently been released in the Indian state of Jharkhand. It was bred using marker-assisted backcrossing with selection for multiple quantitative trait loci (QTL) for improved root growth to improve its performance under drought conditions. It is an early maturing, drought tolerant and high yielding variety with good grain quality suitable for the direct seeded uplands and transplanted medium lands of Eastern India.

Genetics of high-rise riceLaurentius A. C. J. Voesenek and Julia Bailey-Serres

Nature, 460: 959-960

Hattori, Y. et al. Nature 460, 1026-1030 (2009).

SNORKEL1, SNORKEL2 genesTHREE different gene regions on THREE different chromosomesTransferred to short, non-flood responsive rice by natural breeding assisted by MAS

The Use of GM in Agriculture - SummaryThe New Genetics tells us that GM in crop production:

Has no basic scientific foundationConceptually and technically flawed; not technically neutralYesterday’s technology based on yesterday’s understanding of genes and genetics

GM possesses inherent unpredictability for health and the environment which is currently impossible to quantify.The release of viable GMOs into the environment is not justified and possibly irresponsible as once released into the environment GMOs cannot be recalled.

There already exist proven alternatives to meet future food needs in a sustainable manner, a role that GM in its current form is unable to fulfil:

"Genetic-modification technologies just treat the symptoms rather than dealing with the causes", Hans Herren, president of the Millennium Institute, Arlington, Virginia (USA); co-chair of the International Assessment of Agricultural Knowledge, Science and Technology for Development (IAASTD). [Nature, 455: 850-852, 2008].

The Precautionary Principle

"When an activity raises threats of harm to human health or the environment, precautionary measures should be taken, even if some cause and effect relationships are not fully established scientifically"

‘Wingspread Statement on Chemically-Induced Alterations to immune system.’ Environmental Health Perspectives, 104:4, August 1996.

Random insertion or splicing of the GM gene:Insertional Mutagenesis

Foreign gene or “transgene” unit

Random Insertion/Splicing

Host genome

Disruption of host gene functions at short/long distances and even on separate chromosomes

GM gene insertion:Selects for active regionsDirect gene disruptionNot a “clean” process; deletions (loss) of host genesGM gene element mediated disturbances

The Mutational Consequences of Plant Transformation

Jonathan R. Latham, Allison K.Wilson and Ricarda A. Steinbrecher

Journal of Biomedicine and BiotechnologyVolume 2006, Article ID 25376, Pages 1–7

Tissue culture phase and gene insertion process combine to cause “… genome-wide mutations can number from hundreds to many thousands per diploid genome. Despite the fact that confidence in the safety and dependability of crop species rests significantly on their genetic integrity, the frequency of transformation-induced mutations and their importance as potential biosafety hazards are poorly understood.”

Potential Health Effects of GM Foods : Some Current Evidence for Unexpected Toxic and Allergenic Events

Laboratory animal feeding studies with GM food raise worrying health concerns

•Rats fed GM tomatoes developed stomach ulcerations

•GM peas caused allergic reactions in mice

•Rats fed GM oilseed rape developed enlarged livers, often a sign of toxicity

•GM potatoes fed to rats caused excessive growth of the lining of the gut similar to a pre-cancerous condition

The USA Experience• No baseline data - where did we start from?• No labelling; no exposure data - who eats what?• GM food ingredients at present account for only a

small part of the US diet (maize, less than 15%; soya bean products less than 5%)

• No human feeding trials• No official epidemiological data• If GM food was causing changes to common

conditions (e.g. allergy, auto-immune disease, cancer) there is absolutely no way that we could know!

• Scientifically indefensible, uncontrolled experiment!!

Bt toxin Impact on Health - Generally unknownArtificial and totally novel; constructed from modified genes of a

soil bacterium, a reservoir of more than 100 Bt insecticides

Ex. 44% difference in GM Bt176 maize

Consequences of GM Mutagenic EffectsDisturbed structure and nutritional composition

Consequences of GM Mutagenic Effects Disturbed structure and nutritional composition

Effects of low doses of Roundup herbicide

Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Gasnier C, Dumont C, Benachour N, Clair E, Chagnon MC, Séralini GE.Toxicology, 2009 Jun 17. [Epub ahead of print].

Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells. Benachour N and Seralini, GE. Chem Res Toxicol, 22: 97-105, 2009.

Time- and dose-dependent effects of roundup on human embryonic and placental cells. Benachour N, Sipahutar H, Moslemi S, Gasnier C, Travert C, Séralini GE.Arch Environ Contam Toxicol, 53: 126-133, 2007.

Control human embryonic 293 cells Same cells treated only 24 h with 0.05% Roundup