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Evaluating the Safety and Efficacy of GMOs in Relation to Food Allergies

Richard E Goodman, FAAAAIProfessor Dept. of Food Science & Technology

University of Nebraska—Lincoln, USA

rgoodman2@unl.edu

Elaine Farley-Zoucha, RD, LMNTEZ Nutrition Consulting, PC

ezoucha@eznutritionconsulting.com

19 April 2018

www.allergenonline.org

Objectives • Understand how the prescribed safety evaluation

process identifies potentially hazardous (allergenic) proteins in GM crops

• Identify the risks of food allergen contamination in prepared and packaged foods compared to the risks of new GM crops

• Understand the impact of labeling foods as containing “GMO”, vs contains peanut, vs. contains gluten, including the impact on food costs

• Explain the pros/cons of food allergy testing vs elimination diet and the role the RDN has in the treatment of food allergies

Experience of RE Goodman – 20 years GMO Safety

• BS Biology & 3 years Grad work Plant taxonomy

• Hollister-Stier Labs (5 years – standardizing pharmaceutical allergenic extracts, 1980-85)

• PhD 1985 - 1990 Dairy Science / Molecular Biology

• Seven years postdoc in Immunology (Cornell & Univ. Michigan)

• Former employee: Monsanto (7 years – GMO food safety assessment- primarily on allergenicity)

• Current (13 years): Research Professor, Univ. of Nebraska Food Allergy 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 2014 after joining in 2007.

– Grants from Gov’t, biotech companies and non-profit organizations

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The Changing Food Supply

Adaptation

GMOs

Genetically Modified Organisms (GMOs): What are they? What foods are they in? and How are they assessed for safety?

• All organisms have DNA, RNA, Proteins and metabolites. 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 “safe foods” (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 in 1980’s….GMO to resist insects and allow low-till farming

GMOs: One functional gene added to thousands in a complex organism for a specific purpose

• First developed and approved GM crops in 1996. Has markedly 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 inhibits

growth of moth larvae (caterpillars) that eat the plants

– Cry 1 A is an alternative to the chemical pesticides including: Thimet, Furadan and Counter chemical insecticides (which have toxicity in mammals including humans)

– 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 mammals

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GMO = One Bacillus thuringiensis gene transferred into GM crops: Cry 1Ab in corn orCry 1Ac in cotton…instead of whole BT organic spray

mRNA protein

Cry 1AProtectionagainst specific insect pests

transcription

translation

DNA (cry 1 A gene) from Bacillus thuringiensistransferred into corn and cotton

MetAla

ProCys

Ala

Ile

LysTrp

Cys Leu

HisTyr

Amino acids

GM Crop Benefits - 85% of soy & corn

Currently ~ 100 GMOs

• Insect resistance

• Herbicide tolerance

• Viral resistance

• Nutritional – high temp frying oil, Omega 3 Fatty Acids

Future GMO products

• Stop plant pathogens

• Golden Rice

• Reduced acrylamide

• Reduced inflammation?

Benefits

• Fewer chemical insecticides, safer ground water

• Lower # farm workers

• Lower energy needs

• More nutritious foods

• Less expensive foods

• Reduce plant pests– Bacteria

– Viruses

– Insects

– Nematodes

Food Supply risks: Potential global GM solutions

Citrus Greening Disease (Huanglongbing) …Global epidemic with Bacterial disease spread by sucking insects that are becoming resistant to chemical pesticides (2 GM varieties)

Bacterial Wilt Disease of bananas -Pepper Proteins

Golden Rice Beta-Carotene

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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– Allergens

– Toxins

– Celiac glutens

– Do nutrient composition in field trials

• Evaluate protein abundance, digestibility by pepsin

• If indicated, do additional tests

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 allergenic 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 in wheat, barley, rye and a few to oats

• FEW PROTEINS in each of these are the hazards

Goodman FARRP 12

A small percent of the entire population are allergic to any one food (most due to specific IgE)MAJOR ALLERGENIC Sampson JACI (2004) 113:805

Table 1. Prevalence of food allergies in the USFood young children adultsMilk 2.5% 0.3%Egg 1.3% 0.2%Peanut 0.8% 0.6%Tree nuts 0.2% 0.5%Fish 0.1% 0.4%Shellfish 0.1% 2.0%Total all foods 6% 3.7%

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Food Sensitization

Protein specific IgE

Elicitation

Allergen database for sequence comparisonsAllergenonline Homepage version 17 (January 2017)http://www.allergenonline.orge

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Results of Bioinformatics• Is the source of the new protein a known

allergenic source or the protein known to be allergenic? YES/NO?

• Is the amino acid sequence nearly identical to a known allergen? YES/NO?

• If YES to either, do serum IgE tests with sera from appropriate allergic subjects!

• OK, or DROP product?

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(Bethune and Khosla, 2008, PLOS Pathol)

Native gliadin with “Q”s (Gln), may be deamidated to “E”s (Glu) by TG2, > immunogenicity

Tissue Transglutaminase (TG2) is a wound healing enzyme, normally x-links basement membrane, not deamidation of food proteins!

Celiac Disease: T cell reaction to glutens of wheat - turns into Autoimmunity: Genetic factor – MHC Class II, DQ 2.5 or DQ8 ~30% of population, only 1.3% have CD

Class

Order

Family

Subfamily

Tribe

Genus

No evidence these induce CD

CELIAC DATABASEFirst version 2012 updated 2017EFSA 2017 demandsThe updated beta version meetsEFSA requirements

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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 fish for a few

• Celiac disease occurs in ~1.3% due to glutens in wheat, barley, rye and a few to oats

• FEW PROTEINS in these are the hazard!

Labels of Allergens processed food can be verified or challenged by CONFIRMATION BY TESTS

Labels of Allergens processed food Can be verified or challenged by BY TESTS

Antibodies against proteins in allergenic sources: (peanuts, eggs etc.)

Validated ELISA or lateral flow strips: manufactured by Neogen, rBiopharm and others

Extraction method can be very important

Laboratory needs certification: ISO 17025:2005FARRP at UNL; Romer; Eurofins; RSSL-UK

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Allergen Labeling of ProductsCan be overly conservative & misleading

Non-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 known

2. Nordlee and Taylor… IgE binding and SPT+

3. Pioneer stopped development did not go to FDA

2. StarLink corn, Cry 9 C ~ 1999 - EPA1. Stable in pepsin, but that was the only “fault”

2. No sequence identity to allergens

3. Low abundance

4. $500 Million lost due to bad regulatory decision

GMOs that have been through the approval process are

AS SAFE as non-GM varieties

So, are these misleading?

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Who do CONSUMERS TRUST for information on vaccines, GMO-free and Gluten-free Diets: Celebrities!

But NOT Hundreds of Controlled Studies by academic or company scientists !

Celebrity voices on GMOsOprah Winfrey Dr. Oz (MD-tv star) Mr. Jeff Smith (anti-GM activist)Unsubstantiated “science” of molecular biologistGilles Seralini in rats!

Experience of Elaine Farley-Zoucha– RDN, LMNT

• University of Nebraska – Lincoln, BS in Nutrition and Dietetics

• University of Iowa Hospitals & Clinics – Dietetic Internship

• EZ Nutrition Consulting, PC – Founder & CEO

• Common Ground – Volunteer for 2 years

• Farmer – Row Crops and Cow/Calf operation

The RDN’s Role in Food Allergies• Identification (Allergens for allergic

consumers)

• Treatment (Avoidance and epipens)

• Support

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Humans are omnivores…We eat, thrive & reproduce on diverse foodsIn “balanced diets”

• Plants– Grain

– Fruits

– Foliage

– Roots

• Animals– Mammals, reptiles, birds. Fish

– Insects

• Fungus / yeasts

• Bacteria

• Jelly fish

COMPONENTS we needDNARNA

ProteinsLipidsCarbohydratesVitaminsMineralsPolyphenolicsEthanol

Immune system needs challengesBacteria, viruses, parasites.. & FOOD

Diagnosis• Symptoms (consistent with known allergies or

CD)

• 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 food

sensitivity occurs when a person has difficulty digesting a particular food and only involves the digestive system. This can lead to symptoms such as intestinal gas, abdominal pain or diarrhea.

• Food allergy is an immune system reaction that occurs soon after eating a certain food. Even a tiny amount of the allergy-causing food can trigger signs and symptoms such as digestive problems, hives or swollen airways

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TreatmentFood Sensitivity

• Elimination Diet

• FodMap Diet

Food Allergy

• Avoid Allergen

Celiac Disease

• Avoid gluten (wheat, barley, rye, maybe oats)

Experimental Treatment

• Anti-IgE Therapy

• Oral Immunotherapy

• Early Exposure Therapy

Support• Educate Public

• Science-based Resources

• Support Groups

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GM Controversy – What seems true to you?

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•Unsubstantiated claims:• Food allergy is

increasing due to GM soybean

• Rats get cancer from eating approved GMO corn

• There is no valid testing for food safety

Successful Biotech Crops