Genetically Modified Crops: Past, Present and Future

Genetically Modified Crops: Past, Present and Future National Institute of Oilseed Products 83 rd Annual Convention March 14, 2017 Gary Marchant, Ph.D., J.D. Lincoln Professor of Emerging Technologies, Law & Ethics gary.marchant@asu.edu

The First GM Food: FlavrSavr Tomato In early 1990s, Calgene develops GM late ripening tomato called FlavrSavr 1992: FDA approves new Variety 1993: Public concerns prompt additional FDA review (food additive) 1994: Final FDA approval, and tomatoes go on market 1997: FlavrSavr tomatoes taken off the market after poor sales

GM Foods Are Now Prevalent in United States In 2016, GM comprised: 94% of U.S. soybean 93% of U.S. cotton 92% of U.S. corn http://www.ers.usda.gov/dataproducts/adoption-of-geneticallyengineered-crops-in-the-us/recent-trendsin-ge-adoption.aspx >70% of all processed foods contain some GM ingredients Over 5 billion acres of GM crops have been planted North Americans estimated to have consumed >1 trillion food servings with GM ingredients

Adoption of genetically engineered crops in the U.S., 2000-16 Source: USDA, Economic Research Service using data from USDA, National Agricultural Statistics Service, June agricultural survey.

U.S. Approved GM Food Events (as of June 2016) 45 corn 34 potato 25 cotton 19 soybean 18 canola 7 tomato 3 sugar beet 4 alfalfa 3 radicchio 2 apple 2 papaya 2 squash 2 rice 2 cantaloupe 1 wheat 1 flax 1 bentgrass 1 plum 1 starch potato http://www.accessdata.fda.gov/scripts/fdcc/?set=biocon

GMOs Demonstrated Benefits Reduce pesticide use Use of less environmentally harmful herbicides Less tilling of soils Water quality protection through reduced soil erosion and run-off Reduced greenhouse gas emissions (less plowing and herbicide applications) Increased yields (less destruction of natural habitat) Reduced fumonisins (mycotoxin)

Figure 2. Impacts of GM crop adoption. Klümper W, Qaim M (2014) A Meta-Analysis of the Impacts of Genetically Modified Crops. PLoS ONE 9(11): e111629. doi:10.1371/journal.pone.0111629 http://127.0.0.1:8081/plosone/article?id=info:doi/10.1371/journal.pone.0111629

National Academy of Sciences (2016)

Earlier NAS Reports National Academy of Sciences (1992): Crops modified by molecular and cellular methods should pose risks no different from those modified by classic genetic methods for similar traits. National Academy of Sciences (2000): there is no strict dichotomy between or new categories of, the health and environmental risks that might be posed by transgenic and conventional plants

European Union (2010) The main conclusion to be drawn from the efforts of more than 130 research projects covering a period of more than 25 years of research and involving more than 500 independent research groups is that biotechnology, and in particular GMOs, are not per se more risky than conventional breeding technologies. - European Commission, A Decade of EUfunded GMO Research (2001-2010)

American Medical Association (2013) There is no evidence that unique hazards exist either in the use of rdna techniques or in the movement of genes between unrelated organisms The risks associated with the introduction of rdna-engineered organisms are the same in kind as those associated with the introduction of unmodified organisms.

American Association for the Advancement of Science (2013) the science is quite clear: crop improvement by the modern molecular techniques of biotechnology is safe. Another misconception used as a rationale for labeling is that GM crops are untested.

Yet GMOs Have Been at Most a Limited Success Strong rejection in EU Growing consumer and market rejection in USA Negative factors: Unnatural Regulatory burdens No obvious direct benefits to consumers Organized opposition Labeling debate

Un-Natural

Yuck Factor GM foods takes mankind into realms that belong to God and God alone - Prince Charles the anti-gmo discourse portrays transgenic organisms in terms of impurity and taboo breaking. They are referred to as pollution or contamination They are described as trespassing natural limits and transgressing boundaries, and sometimes as sinful and profaning sacred limits. -Jakub Kwiecinki, Genetically Modified Abominations?

Biotechnology Is Not New We have recently advanced our knowledge of genetics to the point where we can manipulate life in a way never intended by nature. We must proceed with the utmost caution in the application of this new found knowledge. Luther Burbank, 1906

What is Natural? Example: Corn Corn was created by the Native American Indians some 8,000 years ago by domestication of a wild grass-like plant called teosinte.

Only 4 Naturally Occurring North American Foods Blueberry Jerusalem Artichoke Sunflower Squash Prakash, C.S. (2001). The Genetically Modified Crop Debate in the Context of Agricultural Evolution. Plant Physiology 126:8-15.

Limitations of Traditional Breeding Slow process to develop new varieties. Not uncommon for 8 to 10 years from start to finish using traditional plant breeding techniques. Desired new or improved traits not always present in existing species Disease or insect resistance Physiological improvements Stress tolerance Grain or plant composition Lack of precision Usually get a collection of changes difficult to change just a single gene or trait

Though poorly known, radiation breeding has produced thousands of useful mutants and a sizable fraction of the world s crops, including varieties of rice, wheat, barley, pears, peas, cotton, peppermint, sunflowers, peanuts, grapefruit, sesame, bananas, cassava and sorghum. The mutant wheat is used for bread and pasta and the mutant barley for beer and fine whiskey. The mutations can improve yield, quality, taste, size and resistance to disease and can help plants adapt to diverse climates and conditions. Dr. Lagoda takes pains to distinguish the little-known radiation work from the contentious field of genetically modified crops, sometimes disparaged as Frankenfood. That practice can splice foreign genetic material into plants, creating exotic varieties grown widely in the United States but often feared and rejected in Europe. By contrast, radiation breeding has made few enemies.

Chemical and Nuclear Mutagenesis Over past few decades, many new varieties created by nuclear or chemical mutagenesis Over 2000 varieties in commercial production Shotgun approach induces many other mutations in addition to selected trait National Academy of Sciences: a mutation made by traditional techniques may be accompanied by many unknown mutations, which often have deleterious effects on the organism National Academy of Sciences (1987). Introduction of Recombinant DNA-Engineered Organisms into the Environment: Key Issues (Washington, D.C.: National Academy Press)

PNAS 105:3640-3645 (2008)

Risks from Natural Foods Kidney beans poisonous if undercooked Dozens of people killed each year from cyanide in peach seeds Potatoes with toxic levels of solanine Celery with toxic levels of psoralen Cyanogenic glycosides in cassava, lima beans, bamboo shoots Organic foods higher mycotoxins; food poisoning

No conceptual distinction exists between genetic modification of plants and microorganisms by classical methods or by molecular techniques that modify DNA and transfer genes. - National Research Council

Alan McHughen: Behind Ignorance Percentage of respondents who gave correct answer to the following yes/no questions: Are GM foods in US supermarkets? 48% Do ordinary tomatoes contain genes? 40% Would a tomato with a fish gene taste fishy? 42% If you ate a GM fruit, might it alter your genes? 45% Can animal genes be inserted into a plant? 30% McHughen consumers are not starting from a level field of ignorance, they start well behind ignorance, and must unlearn the incorrect information consumers have come to believe is true but isn t McHughen, Biotech J. (2007)

Regulatory Burdens

Several reasons that biotech companies supporting federal regulations for GM crops and foods: Need to know future regulatory requirements for long-term planning Avoid state-by-state regulatory patchwork Build public confidence Government affirmation of safety useful for defending against liability Create minimum floor of requirements to protect against renegade risk-taking companies

Coordinated Framework In 1980s, much controversy over whether new statutes (or even a new agency) were necessary to regulate biotechnology In 1986, U.S. government published Coordinated Framework for Regulation of Biotechnology Products Commitment to regulating biotechnology using existing federal infrastructure by adapting existing statutes to biotechnology products

Coordinated Framework Central premise: no new laws needed to regulate biotechnology The existing health and safety laws had the advantage that they could provide more immediate regulatory protection and certainty for the industry than possible with the implementation of new legislation. Moreover, there did not appear to be an alternative, unitary, statutory approach since the very broad spectrum of products obtained with genetic engineering cut across many product uses regulated by different agencies. (OSTP 1986)

Three Agencies Regulate Biotech Crops in the US The US Dept. of Agriculture determines whether the crop is safe to grow based on authority to regulate plant pests. For example, is it a threat to become a weed; what are its growth and flowering characteristics? Were any plant pests used in its development (e.g., Agrobacterium)? The Food and Drug Administration determines whether the crop is safe to eat. Is it substantially equivalent to other crops with respect to composition, nutrition, allergenicity, digestibility, etc.? The Environmental Protection Agency regulates crops that have pesticidal properties. Are they safe for humans, for non-target organisms, and for the environment?

Fairness Hundreds of safety tests are required for every GM food product prior to commercialization No safety tests required for non- GMO foods Source: A. McHughen, Pandora s Picnic Basket (2000)

Cost of Developing Biotech Plant Source: CropLife Int l

Biotech Plant: Time to Develop Source: CropLife Int l

Alan McHughen: Flaws in U.S. Regulatory Approach Good regulations serve two purposes: they must provide genuine protection from real hazards (primarily a scientific exercise) and they must also assuage public anxiety to instill confidence (primarily a political objective). Current regulations governing GMOs clearly do not meet the scientific objective and, considering the widespread and continuing public skepticism, do not appear successful in their political purpose.

And Now the Latest Development.

Lack of Direct Obvious Benefits to Consumers

First Generation of GM Foods: Input Traits Insect resistance e.g., Bt corn Herbicide resistance e.g., Round-Up Ready soybeans Plant disease resistance e.g., Papayas resistant to ring-spot virus

Second Generation of GM Foods Improved shelf life and quality of fruits and vegetables Crops with improved nutritional qualities (e.g., more healthy oils, more nutritious proteins) Reduction or elimination of allergens and toxins in foods Functional foods containing vitamins or pharmaceuticals Vaccines in foods Drought and salt-tolerant crops

Improved levels of essential amino acids High-lysine maize: Substitute for synthetic lysine in swine and poultry diets Lysine content in maize grain (mg/kg) 1600 800 0 Non GM GM

Purple Tomatoes Blood Oranges

Low Acrylamide, non Browning Potatoes

Nina Federoff, NY Times Food prices are at record highs and the ranks of the hungry are swelling once again. A warming climate is beginning to nibble at crop yields worldwide. The United Nations predicts that there will be one to three billion mire people to feed by midcentury. Civilization depends on our expanding ability to produce food efficiently, which has markedly accelerated thanks to science and technology. New molecular methods that add or modify genes can protect plants from diseases and pests and improve crops in ways that are both more environmentally benign and beyond the capability of older methods.

Golden Rice Vitamin A deficiency Affects 200 million children and woman About 500,000 children go blind each year 2 million children die each year Golden Rice may provide one of the many solutions Still Many Years Away from Reality

Organized Opposition

Mobilization of Organized GMO Opposition Organic food interests have spent millions supporting anti-gmo groups and campaigns

Commercial Barriers to GM Foods EU (and their trading partners) have restricted GM foods Some restaurants, stores and product manufacturers have banned GM ingredients (e.g., Chipotles, Whole Foods, Annie s) Many other companies trying to source non-gmo ingredients Concern about consumer backlash preventing introduction of other GM foods (eg GM wheat, salmon, etc)

The GMO Labeling Controversy

Regulatory Controversy: Should GM Foods Be Labeled? Major focus of U.S. anti-gm activists to require mandatory labeling of GM foods Other countries (e.g., EU, Japan, Korea) require GMO labeling 403(i) of the FFDCA governs FDA requirements for food labels FDA general policy on food labeling: [C]onsumers must be informed by appropriate labeling, if a food derived from a new plant variety differs from its traditional counterpart such that the common or usual name no longer applies to the new food, or if a safety or usage issue exists to which consumers must be alerted.

Purpose of Labeling: Trojan Horse for Anti-Choice? Recent study in EU found that mandatory labeling had virtually eliminated any ability to choose GM foods e.g., In UK, all major supermarket chains have banned all labeled GM products in response to pressure from same groups that lobbied for GM labeling Rep. Dennis Kucinich: I think if we were to come out immediately and say they should be banned, I m not quite sure if we could get the kind of constituency moving forward at this moment on that issue. I think the issue of labeling could achieve that in the short-term. Andrew Kimbrell, Center for Food Safety We are going to force them to label this food. If we have it labeled, then we can organize people not to buy it. David Bronner (Dr. Bronner s Magic Soaps) A labeling law would be the death of GMOs in the US.

Congress Finally Acts In July 2016, as Vermont mandatory GM labeling requirement about to take effect, Congress adopted legislation for a national policy on GM labeling S.764 - National Bioengineered Food Disclosure Standard ( Passed by Senate on July 7, 20-16 by vote of 63-30-7 Passed by House on July 14, 2016 by vote of 306-117-10 Signed by President Obama on July 29, 2016

Main Requirements of Federal GM Labeling Legislation Requires labeling of bioengineered food Labeling can be a text, symbol, or electronic or digital link, but excluding Internet website Uniform Resource Locators not embedded in the link, with the disclosure option to be selected by the food manufacturer Excludes foods served in restaurants Preempts any state GM labeling requirements Requires USDA to define specifics by rulemaking within 2 years e.g. threshold, status of gene editing, etc.

CRISPR Clustered regularly interspaced short palindromic repeats https://www.youtube.com/ watch?v=2pp17e4e-o8

Genome editing Based on cutting DNA & allowing natural repair of the cut DNA sequences DNA sequence to be edited Cut DNA at site to be edited Option 1: Provide a copy of DNA needed to replace gap 1. Insert genes into specific sites 2. Trait correction/conversion Replace one allele with another ATTGGGATCAAGC Desired DNA added at designated spot ATCGGGATCTAGC http://aws.labome.com/figure/te-164-1.png

Source: Perry Hackett

Relative Risks Nature Biotech. (2013) 31: 794-802 Gene-editing Technology regulation uncertain Regulated Low --- Likelihood of Unintended Change High Unregulated

Technologies and Regulation New Item USA Canada Europe Zealand Transgenic Yes Yes Yes Yes Cisgenic Yes Yes Yes Yes Mutant lines No Yes No No Transgenic in pedigree but not in plant No No Yes No Transformed without Agrobacterium No Yes Yes Yes Genome editing: deletions No?? No Genome editing: mutations or insertions Case by case Likely In Court Yes

January 2017 Regulatory Proposals USDA Fed. Reg. Jan. 19, 2017 The Agency s evaluations to date have provided evidence that most genetic engineering techniques. Do not result in a GE organism that presents a plant pest risk. Generally exempts most gene edited organisms from scope of regulated article FDA - Fed. Reg. Jan. 19, 2017 Requests public comment on how to regulate gene edited foods Suggests the agency is inclined to extend voluntary consultation for GM foods to gene edited foods

Released March 9, 2017

Concluding Thought