I. Bringing a Crop to Market - Time Frame: A general comparison for GMOs: From "Sustaining agbiotechnology through lean times", David McElroy Nature Biotechnology 21, 996 - 1002 (September 2003). [a. GMO b. Drug]

PS. Also takes about $500 M to get one crop to market!

II. The regulatory Process for Transgenic Crops in the US: Three main federal agencies - USDA, the EPA, and the FDA. (It's acronym time!)

1. Institutional Biosafety Committee (IBC), similar to an Institutional Review Board (IRB) - monitors potentially hazardous biological research and ensures compliance with biological safety procedures.

2. The USDA: Protects US agriculture and natural resources
Secretary of Agriculture Tom Vilsack

A. Animal & Plant Health Inspection Service (APHIS / USDA): APHIS protects US agriculture from pests and diseases under the Federal Plant Pest/ Quarantine Act (PPA) of 1957, and since 2002, the...

B. Biotechnology Regulatory Services (BRS) (Mission: Compliance and Enforcement)...Yikes!

Bottom Line: is it Safe to Grow?

• APHIS/BRS provides and regulates permits to field test (or 'introduce') transgenic crops.
  
  
• APHIS/BRS assumes that GMOs are pests (under the Federal Plant Pest Act) until proven otherwise. (defined as...'capable of causing damage to the agriculture, forestry, and natural resources of a country' ...)
  
  
• APHIS/BRS requires extensive data on the introduced gene construct, effects on plant biology, field tests over several years (somewhat similar to clinical trials), and effects on the ecosystem, including spread of the gene to other crops or wild relatives

• The BRS is now the main regulatory agency for biotech crops and transgenic livestock, cross-communicates with the EPA and FDA, **plus** works with foreign governments to create acceptable biotechnology standards, agreements, negotiations....(very important $Billion market we want to keep HAPPY)

3. The EPA: Ensures the safety of pesticides
-Lisa P. Jackson was sworn in as EPA Administrator on January 26, 2009.

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA): regulates pesticide distribution, sale, and use; and consequences of pesticide use. This includes plants and microbes producing pesticidal substances. Cry proteins are classified by the EPA as 'Plant-Incorporated-Protectants (PIPs)' - pesticidal substances that plants produce from genetic material added to the plant:

• "Plant-incorporated protectants (PIPs) are pesticidal substances produced by plants and the genetic material necessary for the plant to produce the substance. For example, scientists can take the gene for a specific Bt pesticidal protein, and introduce the gene into the plant’s genetic material. Then the plant manufactures the pesticidal protein that controls the pest when it feeds on the plant. Both the protein and its genetic material are regulated by EPA; the plant itself is not regulated."

EPA Bottom Line: Is it safe for the environment?

• Researchers determine risks of GMO to human health (whether the introduced gene or its product are toxic or allergenic, including and skin and eye irritation, as well as long-term effects including cancer, birth defects, and reproductive and neurological system disorders. )
  
  
• Determine environmental effects of the GMO, including effects on non-target organisms.
  
  
• Determine levels of pesticide residues in plant, soil, and food (with the FDA; see below)
  
  
• Follow an "Insect resistance management plan" (IRM) to slow down development of resistance in the target pest. (*IMPORTANT* Below!)
  
  
• EPA also regulates new uses of existing pesticides, such as use of herbicides together with herbicide-resistant transgenics (RoundUp Ready + BollGard Cotton).

but...do you understand each of the 'no's? Which of the folowing below is a PIP?

	Substance	USDA (safe to grow?)	EPA (safe for environment?)
Dipel (cry protein)	insecticide	no	yes
Bt-corn (cry protein)	insecticide in GMO	yes	yes
Roundup (glyphosate)	herbicide	no	yes
RR soybeans (EPSP protein)	enzyme in GMO	yes	no

4. FDA: ensures the safety of our foods and drugs as part of HHS
Commissioner of Food and Drugs Margaret A. Hamburg, M.D., was confirmed on May 18, 2009 (great bio!!!)

A. Federal Food, Drug, and Cosmetic Act (FFDCA). The FFDCA sets tolerance limits for pesticides and pesticide residues on and in food and feed, including herbicides used on herbicide-tolerant crops. The FDA's biotechnology policy treats substances added to food through genetic engineering as food additives if they are significantly different in structure, function, or amount than substances currently found in food. Since many of the GM food crops do not contain substances that are 'significantly different from those already in the diet' they do not do not require pre-market approval.

Bottom Line: Is it safe to eat? (see next point, though!)

• Currently FDA review is a voluntary, consultative process (stay tuned) to determine the safety of GM food, but since companies do have a legal obligation to ensure that food they sell meets required FDA safety standards, all manufacturers to date have voluntarily submitted their products for FDA review.
  
  
• The plant developer consults with the FDA to review safety, nutritional data and allergenicity.
  
  
• Additional investigation may be required if the GMO involves known allergens, altered nutrient levels, or antibiotic resistance markers.
  
  
• For instance, the FDA's review of the Flavr Savr "was requested by the tomato's developer, Calgene. They later submitted a food additive petition due to the presence of the kan-r gene. The FDA did not require special labeling for Flavr Savr tomatoes, since they maintained the essential characteristics of traditionally developed tomatoes".
  
  
• Although Ag-Bio companies consult with FDA staff and present large amounts of data on food safety, the lack of a formal review and approval process prevents that data from being part of the public record, and may reduce consumer confidence.

And just why is the FDA a voluntary step?

• 1994: FDA's policy for Foods developed by Biotechnology "Based upon the extensive history of safety of plant varieties developed through agricultural research, FDA has not found it necessary to review the safety of foods derived from new plant varieties. ...Substances that have a safe history of use in food do not require extensive premarket safety testing."
  
  
• 2000: FDA to strengthen Pre-Market review of Bioengineered Food: "Although the current consultative process has worked well, and the agency believes it has been consulted on all bioengineered foods currently on the market, FDA will require developers to notify the agency of their intent to market a GM food at least 120 days before marketing." (Note this is still being developed.)
  
  
• 2002: Genetically Modified Foods: Experts View Regimen of Safety Tests as Adequate, but FDA's Evaluation Process Could Be Enhanced  The GAO recently released a report (May 23, 2002) critical of the process of regulating GMOs, particularly on the role of the FDA: Summary: "As biotech foods grow more complex with multiple beneficial traits — corn, for example, that is both insect resistant and contains higher levels of vitamin E — premarket testing procedures will need to improve as well."

5. Beyond the US: International regulations

1. The European Union (EU) Until recently, the EU had an "overseas-market barrier" - a moratorium preventing importation of GMOs form the US. This cost farmers and distributors in the US billionsof dollars in export losses since 1998. (Why?)

2. World Trade Organization (WTO) goal is to create and maintain free and open international trade. They have always had a stormy relationship between GMO and non-GMO factions (mainly the USA and Argentina arguing with the EU).

June 2003: Trade dispute over GMOs: "The continuing lack of new approvals for GMOs in Europe has prompted the US to officially request WTO consultations with the EU. "The illegal moratorium [in Europe] has cost US farmers in excess of $1 billion in terms of lost grain exports... The Europeans have continued to present new non-science based hurdles at every juncture… We have no choice but to take this matter before the WTO for dispute resolution." Lisa Dry US BIO

Feb 7, 2005: Dispute resolution: Academic and Science Community Applauds WTO GMO Ruling "The WTO ruling today directs the EU to end its defacto moratorium on biotechnology-improved crops. Over 3,400 scientists, including 25 Nobel Laureates such as Dr. James Watson, Dr. Arthur Kornberg, Dr. Marshall Nirenberg, Dr. Paul Berg et al. have signed a declaration of support for agricultural biotechnology sponsored by the AgBioWorld Foundation. "The favorable ruling gives EU farmers the option to use safe, approved and proven tools to grow food crops, and gives consumers the right to choose those foods in grocery stores." (not everyone agrees...Union of Concerned Scientists)

19 May 2004 EU ends 6-year import ban on genetically modified food. "Under the new EU import rules, any biotech corn must be clearly labelled as harvested from a genetically modified plant. The decision applies to all 25 EU countries for 10 years."

 

3. The United Nations Cartagena Protocol on Biosafety went into effect on Sept 11, 2003, after the 50th nation signed in support: (6 October 2009 update: Reducing the Environmental Risks of Biotechnology)

• The first legally binding international agreement governing the transboundary movement, handling and use of living modified organisms (LMOs) resulting from biotechnology, also taking into account potential risks to human health and biological diversity.
  
  
• The agreement was approved by both proponents and opponents of transgenic crops.
• -- What do you think: Did the US sign? YOU TELL ME! The protocol required ratification by 50 nations before it took effect.
  
  
• International shipments that "may contain" transgenic food products must be labeled. The exact nature of the genetic modification need not be specified, but the agreement calls for negotiations on more specific labeling requirements in the future.
  
  
• Governments may use the so-called "precautionary principle" that states:
  • "where there is a threat of significant reduction or loss of biological diversity, lack of full scientific certainty should not be used as a reason for postponing measures to avoid or minimize such a threat"
    
    
• This gives countries the right to bar import of a transgenic product even in the absence of conclusive evidence that the product is not safe, allowing bans "when governments fear imported GMOs in food may have an adverse effect on biological diversity or human health"

Moral: "Public acceptance of GM foods ultimately depends on the credibility of the testing and regulatory process, which must be as rigorous as possible and based on the soundest of science. Given the striking increase in the number and types of transgenic plants on the market, the federal agencies responsible for regulating them must take steps to better coordinate their work and to expand public access to the regulatory process." From Cultivating Public Confidence in Genetically Modified Crops National Academy of Sciences, April 28, 2000

Objectives:

1. Bt and bugs: What is IRM? What is a refuge and why does the EPA require its use with Bt Corn and cotton? Are refuges working in practice?
2. Bt and Monarchs: What is the effect of Bt crops on Non-target insects? Compare the findings of the Losey et al Nature paper (now retracted) with the EPS's 2000 report and Sears et al. 2001 PNAS paper
3. Why isn't GM food labeled as such by the FDA? - Explain the reasons!
4. Explain the major findings of the developing discovery (8/06) of the escape of RoundUp Pro Creeping Bentgrass: Grass Created in Lab Is Found in the Wild . How does this finding relate to the StarLink Taco Shells, and the Prodigene story?
5. Explain the roles of the USDA (APHIS/BRS), the FDA, and the EPA in regulating GMOs.
6. Define PIPs!
7. Explain WHY the FDA approval is NOT required for GM crops!
8. What is the Cartagena Protocol on Biosafety and what are two of its main provisions?

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