Genetically Modified Crops:

Past, Present and Future

Gary Marchant, Ph.D., J.D .

Lincoln Professor of Emerging Technologies, Law & Ethics

gary.marchant@asu.edu

National Institute of Oilseed Products

83rd Annual Convention

March 14, 2017

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/data-products/adoption-of-genetically-engineered-crops-in-the-us/recent-trends-in-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., 2000-16Source: 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 useUse of less environmentally harmful

herbicides Less tilling of soilsWater 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.0111629http://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 EU-

funded 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?

“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

Biotechnology Is Not New

Corn was created by the

Native American Indians

some 8,000 years ago by

domestication of a wild

grass-like plant called

teosinte.

What is Natural? Example: Corn

Only 4 Naturally Occurring

North American Foods

Prakash, C.S. (2001). The Genetically Modified Crop Debate in the Context of Agricultural Evolution. Plant Physiology 126:8-15.

BlueberryJerusalem

Artichoke

Sunflower Squash

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 speciesDisease or insect resistance

Physiological improvements

Stress tolerance

Grain or plant composition

Lack of precisionUsually 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 mutagenesisOver 2000 varieties in commercial production

“Shotgun” approach induces many other mutations in addition to selected traitNational 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 under-cooked

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

0

800

1600

Non GM GM

Lysine content in maize grain (mg/kg)

Purple

TomatoesBlood 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.

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

CRISPR

“Clustered regularly interspaced short palindromic repeats”

https://www.youtube.com/

watch?v=2pp17E4E-O8

Genome editingBased on cutting DNA & allowing natural repair of the cut

http://aws.labome.com/figure/te-164-1.png

DNA sequences• DNA sequence to be edited

• Cut DNA at site to be edited

1. Insert genes into specific sites

2. Trait correction/conversion

• Replace one allele with another

ATTGGGATCAAGC

ATCGGGATCTAGC

Provide a copy of DNA needed to replace gap

• Desired DNA added at

designated spot

Option 1:

Source: Perry Hackett

Relative Risks

Gene-editing Technology

regulation uncertain

Nature Biotech. (2013)

31: 794-802

Low --- Likelihood of Unintended Change High

Unregulated

Regulated

Technologies and Regulation

Item USA Canada EuropeNew

ZealandTransgenic 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