Biosafety Protocol Update: The "Precautionary Approach" and Zero Tolerance for Unapporved Varieties

Thomas P. Redick

With the passage of the biosafety protocol, and the ongoing debate over the interpretation of that document, commodities shipments from the U.S. to the European Union ("EU") and Japan are being threatened by a standard for assessing the risks of genetically modified organisms ("GMOs") that many argue is unscientific. This article explores the current "zero tolerance" regulatory environment for GMOs produced using an antibiotic resistant marker gene (e.g., the varieties of "B.t. corn" denied entry to the EU). When regulators single out biotechnology process for a "zero tolerance" standard, they isolate a single DNA sequence as something worthy of more regulatory protection than a known carcinogen or radioactive isotope. If we follow this mutant strand of DNA on its journey through the world, we will find truth to be much stranger than fiction.

On January 29, 2000, the text of the long-awaited biosafety protocol – the Cartagena Protocol on Biosafety ("Protocol") to the Convention on Biological Diversity ("CBD") – was agreed to by representatives of nearly every trading partner of the United States. A few days after the Protocol text issued from the Montreal meeting, the EU announced that its interpretation of the "precautionary approach" would allow it to continue its "Great Refusal" of commodity shipments from the United States without running afoul of its obligations under trade agreements. In March meetings of committees of the Codex Alimentarius ("Codex," the international standard-setting body for food safety, an agency of the United Nations Food and Agriculture Organization ("FAO")), the EU sought adoption of the "precautionary approach" as a general principle of food safety (specific to GMOs). More recently, the EU nations have initiated efforts to impose documentation requirements on commodities shipments as part of the further implementation of the Protocol. As a result, the U.S. is addressing the issue of what "precaution" is appropriate to a commodities shipment containing GMOs on two fronts: in Codex and in the Protocol. It is apparent, based upon the EU’s most recent amendments to its Regulation 90/220, that the EU will consider the presence of a few molecules of antibiotic resistant DNA sufficient to bar commodities shipments from the U.S.

It is difficult to rationalize decisions barring entire commodities shipments based on a few molecules of DNA, particularly when molecules of various toxins present in commodities shipments (at tolerances set well below levels known to be safe) are not barred. As a result, the EU has made a concerted effort to extend its "precautionary" interpretation of the Protocol into the realm of trade law and influence the World Trade Organization ("WTO"). The EU has proposed that the "precautionary approach" in the Protocol should be adopted as a "general principle" by the Codex. The EU would then use the "precautionary approach" as a general principle, allowing reversal of the burden of proof for issues relating to food safety and environmental impacts of GMOs. With this reversal of the burden of proof, the EU and other nations would seek to support their "zero tolerance" standard for unapproved GMOs with "scientific" evidence of vanishingly small "threats" to human health (such as the use of antibiotic resistance marker genes).

GMOs in U.S. export crops are increasingly common, with half the soybeans and one-third of the corn planted to GMOs. Soybeans are still making it to the EU, in part due to the absence of antibiotic resistant marker genes. Acting separately, both the EU and Japan have adopted "zero tolerance" for unapproved varieties of GMO crops arriving in commodities shipments bound for food processing. Nations adopting "zero tolerance" for unapproved varieties are expected to use the "precautionary approach" to justify an irrational fear of sequences of DNA. Rather than accept small levels of inadvertent commingling (called "adventitious" in industry parlance), these overseas regulators are requiring shipments to test out to "zero" GMO content in ultra-sensitive DNA testing.

As a result of this "zero tolerance" policy, much of the corn grown in the U.S. is expected to fail the test for export to the EU (at a rate of about $200 million per year in lost exports). See U.S. Department of Agriculture ("USDA") web site at http://usinfo.state.gov/admin/006/eur108.htm. Shipments to Japan are also at risk. While soybeans are being segregated from unapproved varieties, the threat posed by "zero tolerance" for unapproved GMO varieties stifles innovation and increases production costs, without any identifiable benefit to consumers. Protecting consumers from harmless strands of DNA is a costly endeavor with vanishingly small, if non-existent, benefits to consumers overseas.

The EU’s Interpretation of the "Precautionary Approach"
Simply stated, the EU considers the "precautionary approach" in the biosafety protocol to require an importing nation to take extra precautions in evaluating the food safety risks posed by GMOs. The EU considers a "precautionary approach" to food safety to be justified by raising any hypothesis of food safety risk that may require testing – even risks that a near-consensus of scientific experts find "vanishingly small" in relation to genuine food safety concerns, like the presence of an antibiotic resistant marker gene. In contrast, the U.S. would not restrain trade pending testing of every remote and hypothetical food safety risk that could be posited for a particular GMO.

The risks identified in several decades of scientific literature evaluating risks of GMOs are now familiar to risk assessors: (1) allergenicity – where a genetically modified food contains a known or unknown allergen; (2) toxicity – if a new toxin were to be introduced unintentionally; (3) creation of resistant pathogenic organism (e.g., if the antibiotic resistance gene in B.t. corn were to "jump" to a toxic strain of E.coli, or herbicide resistance to a related weedy species of rapeseed); and (4) creation of resistant agricultural pests due to selection pressure from GMO "plant pesticides" such as B.t. corn. The U.S. convened an eminent panel of scientists and policymakers under the direction of the National Research Council, the operating arm of the National Academy of Sciences, and found that U.S. regulatory policy, on balance, was effectively addressing these risks. See http://www.nap.edu/books/0309069300/html/ . The report issued by this panel was assailed from both sides of this polarized issue, with pro-biotechnology commentators accusing the report of singling biotechnology out as a process, while opponents of agricultural biotechnology considered the panel biased in favor of the technology.

The EU prepared a white paper on food safety in January 2000 that stated its position. See http://europa.eu.int/comm/dg24/library/pub/pub06_en.pdf . Echoes of the "precautionary" sentiment surfaced in scientific journals, questioning whether the appropriate tests have been used in determining whether allergens or toxins are present in food produced from GMOs. Activists and scientists sympathetic to their cause are contending GMOs should be treated as bundles of food additives, each of which needs to be fed to rats in large doses. (See, e.g., Erik Millstone, Eric Brunner and Sue Mayer, Beyond Substantial Equivalence, 401 Nature 525 (Oct. 7, 1999)). This foray into treating food as if it were a drug has been greeted with alarm by leading experts in food safety. (See Steven L. Taylor, Susan L. Hefle (letter response published in 402 Nature 575 (Dec. 9, 1999). See also Peter Kearns, Paul Mayers, Substantial Equivalence is a Useful Tool (letter response published in 401 Nature 640 (Oct. 14, 1999)). The Organization for Economic Cooperation and Development ("OECD") revisited its version of the "substantial equivalence" standards and suggested that there is a "possibility" of adverse effects from genetically modified food in the future in its report on the Agricultural Outlook.

In response to consumer concerns at home and abroad, the U.S. Food and Drug Administration ("FDA") is seeking public comment on its policy of substantial equivalence, and bills are pending in the U.S. Congress that would direct the FDA toward a "food additive" approach. See S. 2315, the "Genetically Engineered Food Safety Act," introduced March 29, 2000, by Senators Daniel Patrick Moynihan (D-NY), Barbara Boxer (D-CA) and Harry Reid (D-NV), and a similar bill, H.R. 3883, introduced by Rep. Dennis Kucinich (D-OH). A report released by the Committee on Science’s Subcommittee on Basic Research assesses the benefits and risks of genetically modified plants and plant-derived foods, and recommends changes in federal regulation. See Seeds of Opportunity: An Assessment of the Benefits, Safety, and Oversight of Plant Genomics and Agricultural Biotechnology, http://www.house.gov/science/smithreport_041300.pdf.

Under the "substantial equivalence" standard, new genetically modified foods are reviewed for new allergens or other toxins in a process more elaborate than any prior food – leading many food safety experts to conclude that they are probably much safer than those already on the market (which are "generally recognized as safe" but may pose some unknown allergy and toxicity risks). Using this process, GMOs from the U.S. have generally qualified as "substantially equivalent" under long-standing regulatory standards developed by the OECD. When a known or suspected allergen is found, the GMO requires labeling (and, in practice, is simply not marketed at all, but returns to the lab where biotechnology can create a hypoallergenic variety).

The U.S. has supported "substantial equivalence" as the only scientifically supportable standard for review of GMO food safety. If the EU succeeds in taking the "precautionary approach" language in the Protocol and inserting it into the Codex process, the EU will greatly expand the potential impact of the Protocol on U.S. grain exports.

What the EU could not achieve in the Protocol talks (a global extension of its current moratorium on new GMOs), it may eventually impose through the marketplace’s reaction to the "zero tolerance" standard for unapproved varieties. In adopting a "zero tolerance" policy, the EU has spun out a web of commercial reactions that reaches throughout the chain of commodity commerce. If allowed to continue for long, "zero tolerance" of unapproved DNA would have impacts all the way back to the lab benches of innovators working on the next generation of innovation in agricultural biotechnology. "Zero tolerance" standards create a web so fine that any perturbation caused by the commingling of unapproved DNA (a single grain of corn, one soybean, or the DNA-laced residue of an unapproved GMO) at any point in the chain of commerce could result in the loss of an entire shipment. While segregation costs may promote innovation in genetic tests for sale to EU regulators, it is expected to have a chilling effect on creation of new GMO varieties.

In adopting "zero tolerance" due to concern over remote health risks, the EU creates a global disincentive for innovation in agricultural biotechnology that could be detrimental to human health by impeding beneficial innovation. Unfortunately, in the post-protocol "zero tolerance" environment, a pharmaceutical application of a specialty crop emerging from the pipeline (e.g., "Golden Rice" with Vitamin A or other "nutriceutical" innovations) will enter a more hostile receiving environment when it is test marketed in the U.S. The innovator cannot escape the threat posed by "zero tolerance" for an unapproved variety simply by deciding not to export his own crop.

A "Precautionary Approach" to Biodiversity Conservation
The EU’s continuing restraints on approval of GMOs for import may be inconsistent with the objectives of the CBD and the Terms of Reference for the Protocol, particularly if the EU’s "precautionary approach" to food safety were to be copied by a developing country. The primary objectives of the CBD are to conserve biological diversity, find sustainable uses for it, and share the benefits with everyone involved in the process. Developing countries have significant interests in ensuring food security and their own biotechnology industries, and to draw wealth from the DNA mother lode that biodiversity represents. As a result, for any GMOs that pose a low known risk to human health and the environment while promising significant benefits to the primary goal of biodiversity, both the CBD and the Protocol should require prompt approval and distribution of those GMOs. Any anti-GMO decision (or non-decision pending review) that results in the hastening of destruction of biological diversity contradicts the express mandate of the Protocol and the Convention it amends.

A "precautionary approach" to new GMOs that cannot coexist with the innovative use of genetic resources elsewhere in the world should not be tolerated in the CBD. The eminent environmentalist and microbiologist Rene Dubos foresaw the potential for technology transfer to developing countries in the earliest days of biotechnology. Stating that the "potential benefits are large and the dangers purely hypothetical," he urged the developing nations to share in the wealth of knowledge that biotechnology offers: "DNA recombinant research can be carried out almost anywhere, because it requires only simple equipment, unless put into a cumbersome straight jacket by unreasonable safety measures. . . . It enables even poor countries to engage in the most sophisticated field of biological science. It promises practical applications in medicine, agriculture, and industry." Gerard Piel and Osborn Segerborg, Jr., THE WORLD OF RENE DUBOS at 243 and 244 (Henry Holt, 1990), reprinted from The New York Times (Apr. 21, 1977). This vision of an interdependent, innovative developing world making sustainable use of genetic resources should not be lost in the current media focus on the high-paying patents of multinationals and the doom-saying prophets of Greenpeace.

To prevent the transboundary migration of the EU’s "precautionary approach" to food safety, the U.S. will need to gather scientific data proving that low risk GMOs help to improve human health and the conservation of biodiversity. This data would help to overcome this "precautionary" assumption and prevent the EU’s interpretation from spreading intolerance of agbiotech around the world. With both the law and the facts rebutting its presumption of hazardous DNA sequences, the EU will have to reconsider its "zero tolerance" standard for innovation in agricultural biotechnology.

The "Science" Behind "Zero Tolerance": Peering Through the Emperor’s New Clothes
The EU’s decision to ban antibiotic resistant marker genes in its recent amendments to Regulation 90/220 (an ex post facto endorsement of the EU’s prior rejection of Ciba’s B.t. corn due in part to the use of an antibiotic resistance marker) illustrates the "fear of DNA" at its most extreme form. Long before the EU had its unfortunate encounter with mad cows and lost faith in the science of risk assessment, agbiotech research labs around the world used antibiotic marker genes to help them locate the genes they had inserted in crops (e.g., making the B.t. corn germplasm resistant to antibiotics). Researchers correctly predicted that this gene, if it were ever to emerge from the corn nucleus to enter the gut of a cow intact, would promptly break down to biologically inactive nucleic acids and be absorbed as food.

The FDA studied antibiotic resistance in the Calgene "Flavr Savr" tomato (the first genetically modified food submitted in the U.S.). The FDA found that antibiotics resistant to DNA, while mobile between bacteria, did not have much hope of getting out of the GMO it was implanted in with its mobility intact. The world’s leading experts convened for the FAO and World Health Organization ("WHO"), and largely agreed with the FDA and OECD’s risk assessment process for GMO food risks. The FAO/WHO report called the risk of antibiotic resistance "vanishingly small" and urged everyone to focus on the real risks and benefits.

If antibiotic resistance were portrayed in a pie chart, the share of resistance attributable to GMOs (assuming transfer were proved to occur fairly frequently) would be a "vanishingly small" line on the chart. With feedlots providing cattle with subtherapeutic doses of antibiotics, selection pressure already exists for antibiotic resistant bacteria. These bacteria pose a genuine food safety risk that merits more attention than an extensive risk assessment and "zero tolerance" risk management for the hypothetical emergence of a lone hypothetical bacterium carrying DNA acquired from B.t. corn. When the EU bends over to focus too much attention on the risks of toxic microbes in cowpies, they may miss the charging bull of microbial food safety behind them. More importantly for purposes of the biosafety protocol, the EU ignores the impacts that its "zero tolerance" policy could have on progress toward the broader objectives of the CBD.

While the scientific process of risk assessment has served us well in the U.S., providing years of safe use of biotechnology, the EU’s fear of naked DNA has led to a form of "analysis paralysis" that appears intended to exclude U.S. grain imports that pose no significant risk to human health. With a reasonable tolerance for unapproved GMOs, the EU’s adverse impact on innovation in agricultural biotechnology could be greatly reduced.

As the tolerance for GMO commingling ratchets decreases from 5% GMOs (in Japan for approved GMOs) to 1% (in the EU for approved GMO corn and soybeans) and finally to zero (both the EU and Japan for any unapproved GMO), the measures necessary to achieve those tolerances could become exponentially costly. For example, a self-pollinating crop of soybeans may co-exist with other export-approved soybeans at 10 feet and meet a 5% tolerance. It could require 10 to 20 feet distance to neighboring crops to achieve a tolerance of 1%, with zero percent posing practical challenges and many uncertainties that have yet to be resolved in practice. Safe distances for corn pollen, rapeseed, and other crops pollinating across large distances are much more problematic than soybeans.

Rather than stand idly by while the EU’s regulatory web forms this cocoon of avoidance costs triggered by "zero tolerance" regulation around agbiotech innovation in the U.S., a compelling appeal to the conscience of the EU and the other parties to the CBD should be undertaken. The EU’s "precautionary" approach to food safety should not become an international standard at Codex without a great deal of precautionary analysis of the impact it would have on the future of biotechnology and the conservation of biological diversity.

One unfortunate unintended consequence of "zero tolerance" is the creation of potential nuisance liability for unapproved varieties of GMOs used in agriculture. A grower of crops bound for export could have a claim for private nuisance against a negligent grower of an unapproved GMO variety, if the grower of the unapproved variety does not take appropriate steps to prevent commingling of unapproved varieties (e.g., from pollen drift) during the growing season or post-harvest. Faced with these private nuisance problems, state legislators or regulatory authorities may use whatever tools are available to manage the problem of GMO varieties that are unapproved overseas, including public nuisance statutes and state-level permitting programs. (For further details regarding the law of nuisance and unapproved varieties, see Thomas P. Redick and Christina G. Bernstein, Nuisance Law and the Prevention of "Genetic Pollution": Declining a Dinner Date with Damocles, 30 ELI Environmental Reporter 10328 (May 2000)). If reasonable tolerances for unapproved GMOs could be established throughout the commodities trading partners of the U.S., the threat of commercial nuisance liability from unapproved varieties would be greatly reduced.

"Zero tolerance" for unapproved GMOs creates a barrier to entry for innovators everywhere – particularly the undercapitalized innovators in the developing and transition nations who would like to have the tools to capitalize their genetic resources. A broad range of future innovation could be chilled by these unreasonable "zero tolerance" standards. Innovation is not well served by a surprise regulatory decision that arrives after a ten-year innovation pipeline is reaching its conclusion and a product is ready to market. With sufficient advance notice, the agbiotech industry could address some of these "vanishingly small" risks, perhaps using alternatives to antibiotic marker genes in future innovations.

The CBD should not provide a home for a "zero tolerance" food safety standard that prevents progress in agricultural biotechnology. All innovation in food production should be shared as widely as possible with developing countries under the terms of the CBD. As a "precautionary approach" to new DNA sequences spreads around the globe, the most important form of innovation that the Convention would promote – the fullest possible utilization of genetic resources – would be stifled.

While the Protocol is a bundle of contradictory statements that reflect the differing positions of the parties, and lawyers will be debating the contradictions for many years to come, there is one clear path through the Protocol and the 21st Century. If the Protocol is interpreted in the spirit of conservation and sustainable development, the parties to the Protocol will embrace innovation in biotechnology along with the science of careful risk assessment. Properly applied, the Protocol will lead nations seeking improvements in human health and environmental protection to adopt biotechnology more rapidly than they otherwise would. If the Protocol is read to focus "precautionary approach" only at the risks of GMOs, as certain misguided Europeans would have the world do, the Protocol could fail in its mission of protecting biodiversity.