Goodman And Farley-Zoucha Presentation NAND 26 April

Evaluating the Safety and Efficacy ofGMOs in Relation to Food AllergiesRichard E Goodman, FAAAAIProfessor Dept. of Food Science & TechnologyUniversity of Nebraska—Lincoln, USArgoodman2@unl.eduElaine Farley-Zoucha, RD, LMNTEZ Nutrition Consulting, PCezoucha@eznutritionconsulting.com19 April 2018www.allergenonline.orgObjectives Understand how the prescribed safety evaluationprocess identifies potentially hazardous (allergenic)proteins in GM crops Identify the risks of food allergen contamination inprepared and packaged foods compared to the risksof new GM crops Understand the impact of labeling foods ascontaining “GMO”, vs contains peanut, vs. containsgluten, including the impact on food costs Explain the pros/cons of food allergy testing vselimination diet and the role the RDN has in thetreatment of food allergiesExperience of RE Goodman – 20 years GMO Safety BS Biology & 3 years Grad work Plant taxonomy Hollister-Stier Labs (5 years – standardizing pharmaceutical allergenicextracts, 1980-85) PhD 1985 - 1990 Dairy Science / Molecular Biology Seven years postdoc in Immunology (Cornell & Univ. Michigan) Former employee: Monsanto (7 years – GMO food safetyassessment- primarily on allergenicity) Current (13 years): Research Professor, Univ. of Nebraska FoodAllergy Research and Resource Program– Manager of AllergenOnline.org– Lead Investigator on a number of GM safety studies– Chair of the WHO / IUIS Allergen Nomenclature Subcommittee 2014after joining in 2007.– Grants from Gov’t, biotech companies and non-profit organizations1

The Changing Food SupplyGMOsAdaptationGenetically Modified Organisms(GMOs): What are they? What foods are they in?and How are they assessed for safety? All organisms have DNA, RNA, Proteins andmetabolites. Most have 10,000 genes/proteins Humans have selected plants for genetic advantages– Growth under certain conditions– Nutrients– Food Processing attributes Humans in different geographies have different “safefoods” (US, EU, China, India, Japan, Thailand) 7.5 Billion People 9.5 Billion by 2050! How will we feed them all? Scientists started transferring DNA in1980’s .GMO to resist insects and allow low-tillfarmingGMOs: One functional gene added to thousandsin a complex organism for a specific purpose First developed and approved GM crops in 1996. Hasmarkedly reduced insecticide applications Bacillus thuringienis: 1 gene out of 5,000 genes &proteins, this bacteria used as an organic pesticide– GM Plants express Cry 1 Ab or Cry 1 Ac protein that inhibitsgrowth of moth larvae (caterpillars) that eat the plants– Cry 1 A is an alternative to the chemical pesticidesincluding: Thimet, Furadan and Counter chemicalinsecticides (which have toxicity in mammals includinghumans)– Cry 1 A has no toxicity in mammals at 5 g per kg body weight– Cry 1 A has no known allergenicity– Cry 1 A has no anti-nutrient effects in mammals2

GMO One Bacillus thuringiensis gene transferredinto GM crops: Cry 1Ab in corn orCry 1Ac in cotton instead of whole BT organic sprayDNA (cry 1 A gene) from Bacillus thuringiensistransferred into corn and cottonmRNAproteinAmino acidstranslationLystranscriptionIleMetAlaCry 1AProtectionagainstspecificinsectpestsHisTrpTyrCys LeuAlaCysPro7GM Crop Benefits - 85% of soy & cornCurrently 100 GMOs Insect resistance Herbicide tolerance Viral resistance Nutritional – high tempfrying oil, Omega 3Fatty AcidsFuture GMO products Stop plant pathogens Golden Rice Reduced acrylamide Reduced inflammation?Benefits Fewer chemicalinsecticides, saferground water Lower # farm workers Lower energy needs More nutritious foods Less expensive foods Reduce plant od Supply risks: Potentialglobal GM solutionsBacterial Wilt Disease ofbananas -Pepper ProteinsGolden RiceBeta-CaroteneCitrus Greening Disease (Huanglongbing) Globalepidemic with Bacterial disease spread by sucking insects thatare becoming resistant to chemical pesticides (2 GM varieties)3

Basic GM Safety Evaluation 10 million Evaluate the gene source Literature / www– Allergenicity– Toxicity Function of the gene and protein, metabolites Sequence comparison to known––––AllergensToxinsCeliac glutensDo nutrient composition in field trials Evaluate protein abundance, digestibility bypepsin If indicated, do additional testsAllergenic foods & Celiac Disease Out of hundreds of foods most are safe for mostpeople but Peanuts, a number of tree nuts, seeds, are commonallergenic sources for 2% to 6% of consumers Crustacean shellfish are common allergenic sources Wheat & soybeans are moderately common allergens Milk, eggs are common allergenic sources Boney fish – common allergenic sources Celiac disease occurs in 1.3% due to glutens inwheat, barley, rye and a few to oats FEW PROTEINS in each of these are the hazardsA small percent of the entire population areallergic to any one food (most due to specific IgE)MAJOR ALLERGENICSampson JACI (2004) 113:805Table 1. Prevalence of food allergies in the USFoodMilkyoung children2.5%Egg1.3%0.2%Peanut0.8%0.6%Tree al all foodsGoodman FARRPadults0.3%124

Food SensitizationProteinspecific IgEElicitationAllergen database for sequence comparisonsAllergenonline Homepage version 17 (January 2017)http://www.allergenonline.orge5

Results of Bioinformatics Is the source of the new protein a knownallergenic source or the protein known to beallergenic? YES/NO? Is the amino acid sequence nearly identical toa known allergen? YES/NO? If YES to either, do serum IgE tests with serafrom appropriate allergic subjects! OK, or DROP product?6

Celiac Disease: T cell reaction to glutens of wheat- turns into Autoimmunity: Genetic factor – MHC Class II, DQ2.5 or DQ8 30% of population, only 1.3% have CDNative gliadin with“Q”s (Gln), may bedeamidated to “E”s(Glu) by TG2, immunogenicityTissue Transglutaminase(TG2) is a wound healingenzyme, normally x-linksbasement membrane, notdeamidation of foodproteins!(Bethune and Khosla, 2008, PLOS Pathol)ClassOrderFamilySubfamilyTribeGenusNo evidence these induce CDCELIAC DATABASEFirst version 2012 updated 2017EFSA 2017 demandsThe updated beta version meetsEFSA requirements7

Allergenic foods & Celiac Disease Out of hundreds of foods most are safe for mostpeople but Peanuts, a number of tree nuts, seeds, are commonallergens for a few people Crustacean shellfish are common allergens Wheat & soybeans are allergens for a few Milk, eggs for a few Boney fish for a few Celiac disease occurs in 1.3% due to glutens inwheat, barley, rye and a few to oats FEW PROTEINS in these are the hazard!Labels of Allergens processed foodcan be verified or challenged byCONFIRMATION BY TESTSLabels of Allergens processed foodCan be verified or challenged by BY TESTSAntibodies against proteinsin allergenic sources:(peanuts, eggs etc.)Validated ELISA or lateralflow strips: manufacturedby Neogen, rBiopharm andothersExtraction method can bevery importantLaboratory needs certification: ISO 17025:2005FARRP at UNL; Romer; Eurofins; RSSL-UK8

Allergen Labeling of ProductsCan be overly conservative &misleadingNon-GMO,certified vegan,organic greensNot proven safer GMO Risks of Allergy – to 20181. Soybean – 2S albumin from Brazil nut,transferred to soybean in early 1992-19961. Before the allergen(s) of Brazil nut were known2. Nordlee and Taylor IgE binding and SPT 3. Pioneer stopped development did not go to FDA2. StarLink corn, Cry 9 C 1999 - EPA1.2.3.4.Stable in pepsin, but that was the only “fault”No sequence identity to allergensLow abundance 500 Million lost due to bad regulatory decisionGMOs that have been throughthe approval process areAS SAFE as non-GM varietiesSo, are these misleading?279

Who do CONSUMERS TRUST for information onvaccines, GMO-free and Gluten-free Diets: Celebrities!Celebrity voices on GMOsOprah WinfreyDr. Oz (MD-tv star)Mr. Jeff Smith (anti-GM activist)Unsubstantiated “science” ofmolecular biologistGilles Seralini in rats!But NOT Hundreds ofControlled Studies byacademic or companyscientists !Experience of Elaine Farley-Zoucha– RDN, LMNT University of Nebraska – Lincoln, BS in Nutrition andDietetics University of Iowa Hospitals & Clinics – DieteticInternship EZ Nutrition Consulting, PC – Founder & CEO Common Ground – Volunteer for 2 years Farmer – Row Crops and Cow/Calf operationThe RDN’s Role in FoodAllergies Identification (Allergens for allergicconsumers) Treatment (Avoidance and epipens) Support10

Humans are omnivores We eat, thrive & reproduce on diverse foodsIn “balanced diets” Plants––––COMPONENTS weneedDNARNAGrainFruitsFoliageRootsProteins Animals– Mammals, reptiles, birds. Fish– Insects Fungus / yeasts Bacteria Jelly csEthanolImmune systemneeds challengesBacteria, viruses,parasites. & FOODDiagnosis Symptoms (consistent with known allergies orCD) Family History of Allergies Physical Exam Skin Test (Extracts or fresh fruits / veggies) Blood Test (Specific Serum IgE) Elimination Diet Oral Food Challenge (Gold standard but rare)NO PERFECT TEST!Food Sensitivity vs Allergy A food intolerance, or a foodsensitivity occurs when a person hasdifficulty digesting a particular food and onlyinvolves the digestive system. This can leadto symptoms such as intestinal gas,abdominal pain or diarrhea. Food allergy is an immune system reactionthat occurs soon after eating a certain food.Even a tiny amount of the allergycausing food can trigger signs and symptomssuch as digestive problems, hives or swollenairways11

TreatmentFood Sensitivity Elimination Diet FodMap DietFood Allergy Avoid AllergenCeliac Disease Avoid gluten (wheat, barley, rye, maybe oats)Experimental Treatment Anti-IgE TherapyOral ImmunotherapyEarly Exposure TherapySupport Educate Public Science-based Resources Support Groups12

GM Controversy – What seems true to you?Successful Biotech Crops Unsubstantiated claims: Food allergy isincreasing due to GMsoybean Rats get cancer fromeating approved GMOcorn There is no valid testingfor food safety3713

Apr 19, 2018 · Allergenic foods & Celiac Disease Out of hundreds of foods most are safe for most people but Peanuts, a number of tree nuts, seeds, are common allergens for a few people Crustacean shellfish are common allergens Wheat & soybeans are allergens for a few Milk, eggs for a few Boney fi