GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...

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GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
GM Oh?
 A Lay of the Land • Health Impact • What’s Next?

Mary Anne Smith, PhD RD
Evidence Analyst, Practice-based Evidence in Nutrition
GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
Financial Interest Disclosure
(over the past 24 months)

   No relevant financial relationships with any
             commercial interests
GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
Terminology
• GMOs: “organisms (i.e. plants, animals or
  microorganism) in which the genetic material (DNA)
  has been modified in a way that does not occur
  naturally by mating and/or natural recombination” –
 World Health Organization, 2014

• Synonyms: bioengineering, genetic engineering,
  gene biotechnology, recombinant DNA technology
GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
Why Bother with GM?

  Herbicide        Insect         Disease               Stress
  Tolerance      Resistance      Resistance           Resistances

 Pollination   Product Quality      Altered          Stacked Traits
  Control                        Yield/Growth

                                                ISAAA. GM Approval Database. 2018
GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
>10 Million Hectares
1 - 5 Million Hectares
GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
15 Foods (182 Events)             GM Foods in Canada
    Approved to Date          Crop Hectrage in Canada, 2016
Alfalfa (3)                           Grown in 2016                                 Where in Stores?
Apple (3)
Canola (23)                     Alfalfa                                                    Produce
Cotton (25)                     Canola                                        Sweet Corn? • Zucchini • Yellow
Flax (1)                        Corn                                                        Squash
Corn (67)                       Soybean                                               Processed
                                                                                   Canola  4%      Foods
Papaya (1)                      Sugar Beet                                     Oils • Sugars & sweeteners •
                 Non-GM Crops 94%        GM Crops 6%                           Papaya juices and foods • Soy
Potato (27)
                                                                                lecithin, beverages, protein
Rice (2)                            Imported in 2016-17
Salmon                                                                           powders, puddings, tofu •
                                                                                   Soy 1%
Soy (21)                        Cottonseed Oil                                      Processed corn foods
Squash (1)                      Papaya                                             Corn 1%Seafood
Sugar Beet (2)                  Squash                                                      Salmon
                                                                                      Sugar Beet &
Sugar Cane (1)                  Salmon                                                  Meat & Dairy
                                                                                        Alfalfa 0%
Tomato (4)                                                                      *Indirectly, as GM crops are
                                                                                often used as animal feed*
                                                                                CBAN. Where are genetically modified foods? 2018
                                                         USDA. GAIN Report. Canada Agricultural Biotechnology Annual 2017. 2017.
                                         ISAAA . Global Status of Commercialized Biotech/GM Crops: 2016. ISAAA Brief No. 52. 2016
GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
Regulatory Approach: Equivalence
• Premise: GM foods not
  substantially different from non-
  GM counterpart can be treated
  the same way

• Goal: Determine if the GM food
  is as safe as its non-GM
  counterpart

• Followed by: Canada, Australia,
  US and others.
 Zarrilli. Policy Issues in International Trade and Commodities Study Series No. 29. 2005
GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
Getting to Market
                                                               Canada

Approach to risk assessment                       Substantial equivalence
Pre-market safety assessment
Environmental assessment
Field trials
Animal feeding studies
Post-market monitoring
Waste & contingency plans

                               Adapted from: PEN®, 2016: Genetically Modified Organisms Background
GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
GM Labelling in Canada
                                                       • Voluntary labelling standard adopted in
                                                         2004
                                                       • Political and public interest in mandating
                                                         labelling, but efforts unsuccessful to date
                                                               • Bill C-291 – defeated May 2017 at second
                                                                 reading
                                                               • 2018 Canadian survey (n=1046):
                                                                      • 88.6% agree with mandatory labelling
                                                                      • 61% disagree that voluntary labelling is
                                                                        sufficient
USDA GAIN Report, 2017. Canada Agricultural Biotechnology Annual 2017.
Parliament of Canada, undated. Private Member’s Bill C-291. https://www.parl.ca/LegisInfo/BillDetails.aspx?Language=E&billId=8348744
Charlebois et al., 2018. Biotechnology in food: Canadian attitudes towards genetic engineering in both plant- and animal-based foods. Preliminary results.
GM OH? A LAY OF THE LAND HEALTH IMPACT WHAT'S NEXT? MARY ANNE SMITH, PHD RD EVIDENCE ANALYST, PRACTICE-BASED EVIDENCE IN NUTRITION ...
Identifying GM/non-GM in Canada
• Labels in accordance with
  standard - look for “genetic
  engineering” or “not a
  product of genetic
  engineering”                     www.nongmoproject.org

• Third-party audits - e.g. Non-
  GMO Project
• Certified Organic
                                    www.inspection.gc.ca
Health Impact
   Are GM foods safe?
How could GM foods affect our health?
         Toxins

  Allergens

  Antinutrients
                                   Horizontal Gene
                                   Transfer w/ Gut
                                   Microbiome

                     PEN® 2016, Genetically Modified Organisms Background
Do GM foods contain toxins or
antinutrients?
                                     Zdziarski et al., 2014
•   Critical review of toxicity studies (n=21, all 90 days duration)
•   Macroscopic and histological examinations of the GI tract
•   “All studies examining the GI tract concluded that there were no toxicological or
    pathological changes observed that could be related to feeding GM crops to rats”
•   BUT, ++ methodological issues

                             Van Eenennaam & Young, 2014
•   Narrative review of animal performance studies
•   15+ years of feeding trials in cattle, pigs, chicken, sheep, fish and others
•   Includes long term (2 year) and multiple generation (2-5) studies
•   Consistent consensus that the health and performance of GM and non-GM
    groups are comparable
                                                      Zdziarski et al. Environ Int. 2014;73:423-33
                                                      Van Eenennaam & Young. J Am Sci. 2014;92:4255-78.
Are there allergens?
• Dunn et al., 2017
                                                                          ?
   • Systematic review of 83 studies (34 human, 49 animal), no RCTs
   • Studies examined corn (23), wheat (6), rice (12) , soy (14), peanut
     (5), milk (1), other foods (16), GM-related products (9)

           Q1: Are GM                       Q2: Is the use of
          products more                       GM products
          allergenic than                    associated with
        their conventional                  the development
          counterparts?                        of allergies?
                No                                    ???
                                         Dunn et al. Ann Allergy Asthma Immunol. 2017;119:214-22.
Is horizontal gene transfer possible?
• Yes, but no evidence yet of natural
  occurrence
• Is it because there are natural barriers?
   • Dilution of rDNA?
   • Timing?
   • Inhibitory gut material?

• Or is it a detection issue?
• Evidence from narrative reviews
                                          Nicolia et al. Crit Rev Biotechnol. 2014;34(1):77-88.
                                          Rizzi et al. Crit Rev Food Sci Nutr. 2012;52:142-61.
How good is the evidence?

• Secondary analyses to date are not
  systematic reviews or meta-analyses
• Primary research issues:
   1. Volume of studies:
      • 1,409 articles on Pubmed since 2014
How good is the evidence?

• Secondary analyses to date are not
  systematic reviews or meta-analyses
• Primary research issues:
   1. Volume of studies:
      • 31,848 records before 2006 (Vain et al., 2007)
      • 1,409 articles on Pubmed since 2014
   2. Reliance on in vitro and animal models
How good is the evidence?

• Secondary analyses to date are not
  systematic reviews or meta-analyses
• Primary research issues:
   1. Volume of studies:
      • 31,848 records before 2006 (Vain et al., 2007)
      • 1,409 articles on Pubmed since 2014
   2. Reliance on in vitro and animal models
   3. Study duration – how long is long enough?
How good is the evidence?

• Secondary analyses to date are not
  systematic reviews or meta-analyses
• Primary research issues:
   1. Volume of studies:
      • 31,848 records before 2006 (Vain et al., 2007)
      • 1,409 articles on Pubmed since 2014
   2. Reliance on in vitro and animal models
   3. Study duration – how long is long enough?
   4. Conflicts of interest ~ 26% of published
      primary research (Sanchez, 2015)
What’s Next?
 Four things to look out for
1. Mandatory Labelling?
      • In the US, National Bioengineered Food Disclosure Law
        passed in 2016

      • USDA ‘proposed rule’ open for comments until July 3, 2018

      • Ongoing discussions:
             • Labelling of highly refined foods
             • GM yeast and enzyme
             • Thresholds for requiring a label

      • Is Canada next?
                                                  Agricultural Marketing Service, 2018. https://www.regulations.gov/document?D=AMS_FRDOC_0001-1709
Images from: USDA, National Bioengineered Food Disclosure Standard. https://www.ams.usda.gov/sites/default/files/media/ProposedBioengineeredLabels.pdf
2. GM Animals and By-products
• GM Atlantic salmon approved by
  Health Canada in 2016
• 4.5 tons entered Canadian market
  in spring of 2017
• Currently: eggs produced in
  Canada, fish grown in Panama
• Future: entirely produced in
  Canada at a new facility in PEI
• First GM animal – are others
  next?
                   CBAN, 2017. Update on the status of GM salmon production in Prince Edward Island, Canada.
3. Gene Editing with CRISPR/Cas9
                                                        CRISPR guide sequence
• Precise insertion and sequence of novel
  DNA – hence, gene editing
                                       DNA memory sequence
• Greatly decreases risk of random
  mutations
• Bacterial memory system to
  protect from foreign DNA                                                         Cas9

• Should these products be tested the
  same way as those developed with older
  methods?

                                Thurtle-Schmidt & Lo. Biochem Mol Bio Educ. 2018;42(2):195-205.
4. GM Plants as Drug Factories
• “Plant molecular farming” or “pharming” – using GM plants
  to create pharmaceutical proteins
• Examples:
   • Antibodies for HIV, anthrax
   • Vaccines for H5N1, influenza, rabies, rotavirus
   • Drugs for Ebola, Fabry disease, Gaucher disease, malaria

            Potential for:                   Challenges:
  •   Improved speed              •   Dosing for edible vaccines
  •   Lower cost                  •   Plant glycosylation
  •   Improved safety (?)         •   Purification
  •   Edible vaccines (?)         •   Processing
                                                 Yao et al. Int J Mol Sci. 2015;16(12):28549-65.
                                                      Shen et al. Mol Plant. 2018;11(6):776-88.
Everyone is entitled
 to his own opinion,
but not his own facts.
      - Daniel Patrick Moynihan
References
• World Health Organization. Frequently asked questions on genetically modified foods. May 2014 [cited 2015 Sep
  30]. Available from: http://www.who.int/foodsafety/areas_work/food-technology/faq-genetically-modified-
  food/en/
• U.S. Department of Agriculture. Coexistence factsheets. 2015. Available from: ISAAA. GM Approval Database [cited
  2018]. Available from: http://www.isaaa.org/gmapprovaldatabase/default.asp
• ISAAA. Global status of commercialized biotech/GM crops: 2016. ISAAA Brief No. 52. 2016. Available from:
  http://www.isaaa.org/resources/publications/briefs/52/download/isaaa-brief-52-2016.pdf
• Canadian Biotechnology Action Network. Where are genetically modified foods? 2018. Available from:
  https://cban.ca/wp-content/uploads/cban-gm-food-chart-poster-2018-copy.jpg
• US Department of Agriculture GAIN Report. Canada Agricultural biotechnology annual. 2017. Available from:
  https://gain.fas.usda.gov/Recent%20GAIN%20Publications/Agricultural%20Biotechnology%20Annual_Ottawa_Can
  ada_12-21-2017.pdf
• Zarrilli S. International trade in GMOs and GM products: national and multilateral legal frameworks. Policy Issues in
  International Trade and Commodities Study Series No. 29. 2005. United Nations Publication: Geneva Switzerland.
  Available
  from: www.fao.org/fileadmin/user_upload/gmfp/resources/UNITED%20NATIONS%20CONFERENCE%20ON%20TRA
  DE%20AND%20DEVELOPMENT.en.pdf
• PEN®. Genetically Modified Organisms Background. 2016.
• Parliament of Canada. Private Member’s Bill C-291. 2016. Available from:
  https://www.parl.ca/LegisInfo/BillDetails.aspx?Language=E&billId=8348744
• Charlebois et al. Biotechnology in food: Canadian attitudes towards genetic engineering in both plant- and animal-
  based foods. Preliminary results. 2018. Available from:
  https://cdn.dal.ca/content/dam/dalhousie/pdf/management/News/News%20%26%20Events/Dalhousie%20GMO
  %20Food%20Study%202018%20(EN).pdf
• Zdziarski et al. GM crops and the rat digestive tract: a critical review. Environ Int. 2014;73:423-33. Abstract
  available from: https://www.ncbi.nlm.nih.gov/pubmed/25244705
References (cont)
• Van Eenennaam & Young. Prevalence and impacts of genetically engineered feedstuffs on livestock populations. J Am Sci.
  2014;92(10):4255-78. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/25184846

• Dunn et al. The allergenicity of genetically modified foods from genetically engineered crops: a narrative and systematic
  review. Ann Allergy Asthma Immunol. 2017;199(3):214-22. Abstract available from:
  https://www.ncbi.nlm.nih.gov/pubmed/28890018

• Nicolia A, Manzo A, Veronesi F, Rosellini D. An overview of the last 10 years of genetically engineered crop safety research.
  Crit Rev Biotechnol. 2014 Mar;34(1):77-88. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/24041244

• Rizzi et al. The stability and degradation of dietary DNA in the gastrointestinal tract of mammals: implications for horizontal
  gene transfer and the biosafety of GMOs. Crit Rev Food Sci Nutr. 2012;52(2):142-61. Abstract available from:
  https://www.ncbi.nlm.nih.gov/pubmed/22059960

• Sanchez MA. Conflict of interests and evidence base for GM crops food/feed safety research. Nat Biotechnol.
  2015;33(2):135-7. Citation available from: https://www.ncbi.nlm.nih.gov/pubmed/25658276

• Agricultural Marketing Service. National Bioengineered Food Disclosure Standard. 2018. Available from:
  https://www.regulations.gov/document?D=AMS_FRDOC_0001-1709

• Canadian Biotechnology Action Network. Update on the status of GM salmon production in Prince Edward Island, Canada.
  2017. Available from: https://cban.ca/wp-content/uploads/GM-Salmon-International-Bulletin-Oct-2017.pdf

• Thurtle-Schmidt & Lo. Molecular biology at the cutting edge: a review on CRISPR/CAS9 gene editing for undergraduates.
  Biochem Mol Biol Educ. 2018;46(2):195-205. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/29381252

• Yao et al. Plants as factories for human pharmaceuticals: applications and challenges. Int J Mol Sci. 2015;16(12):28549-65.
  Abstract available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691069/

• Shen Q et al. The genome of Artemisia annua provides insight into the evoluation of Asteraceae family and artemisinin
  biosynthesis. Mol Plant. 2018;11(6):776-88. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/29703587
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