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HENRY I. MILLER

GREGORY CONKO

The Science of Biotechnology Meets the Politics of Global Regulation

Global regulation should be guided by science, not unsubstantiated fears.

These are difficult times for agricultural biotechnology. Outside the United States, there is widespread public and political opposition to importing grains grown from recombinant DNA­engineered, or "gene-spliced," seeds. Governments have imposed moratoriums on commercial-scale cultivation of plants, and recombinant DNA­derived foods have been banished by big supermarket chains. Vandalization of field trials by environmental activists is frequent and largely not being prosecuted. The once principally science-driven regulatory agencies of Western Europe are increasingly dominated by politically motivated bureaucrats who capitulate to the pressure of protectionism-minded business interests and hysterical activists.

In the United States as well, regulators have imposed discriminatory, unscientific rules that hinder agricultural and food research as well as product development. Oversight of product testing and commercialization at the Department of Agriculture and the Environmental Protection Agency has long been focused not on the likely risks of products but on the use of the most precise and predictable techniques of genetic modification. In other words, the trigger to regulation has been not product characteristics thought to pose a risk to human health or the environment but merely the use of a new and superior technology. In April 2000, under pressure from antitechnology extremists and the Clinton administration, the Food and Drug Administration (FDA) reversed a much-praised long-standing policy and also toed the line, announcing a new requirement that all gene-spliced foods come to the agency for premarket evaluation.

Opponents of biotechnology raise the specter of various potential threats to the environment and human health--assertions that are supported by neither the weight of evidence nor the judgments of the scientific community. Nevertheless, antibiotech campaigners represent a growing political force, and their demands for a novel legal standard for the evaluation of new technologies are being heard. Under intense political pressure from environmental groups, national and international bodies are introducing more restrictive and burdensome regulatory regimes that fly in the face of scientific consensus. The greatest effect of such regulation will be to hobble the work of academic researchers and small innovative companies that provide the substrate of research on which product development depends. The effect will be to diminish the overall potential application of gene splicing to agriculture and food production, and, in particular, to delay or deny the benefits of the "gene revolution" to the poorest and neediest parts of the world.

The discovery of gene-splicing techniques some 30 years ago was heralded as a signal advance for the future of medicine, agriculture, and other applications. Foods and pharmaceuticals developed with this new biotechnology have been available in the United States and around the world for nearly two decades. During that time, a wide consensus has grown in the scientific community that because gene splicing is more precise and predictable than older techniques of genetic modification, such as cross-breeding or induced mutagenesis, it is at least as safe. In its highly regarded 1987 report, U.S. National Academy of Sciences concluded that "the risks associated with the introduction of recombinant DNA­engineered organisms are the same in kind as those associated with unmodified organisms and organisms modified by other methods." A U.S. National Research Council (NRC) panel two years later went even further, concluding that, "Recombinant DNA methodology makes it possible to introduce pieces of DNA, consisting of either single or multiple genes, that can be defined in function and even in nucleotide sequence. With classical techniques of gene transfer, a variable number of genes can be transferred, the number depending on the mechanism of transfer; but predicting the precise number or the traits that have been transferred is difficult, and we cannot always predict the [behavior] that will result. With organisms modified by molecular methods, we are in a better, if not perfect, position to predict the [behavior]."

Of course, the introduction of species or varieties into new environments can have adverse environmental effects, such as the damage caused by zebra mussels in the Great Lakes or kudzu vines in the South. Similarly, changes in the genetic makeup of plants can change the nutritional and/or toxicological composition of foods derived from those plants. In other words, risk is a function of the characteristics of the original organism, any genetic changes that are made in it, and the environment into which it may be introduced. But none of the risks that may be associated with gene-spliced organisms is inherent in the method of production, and certainly none is unique to recombinant DNA manipulation. Consequently, the 1987 and 1989 reports also advised that judgments about safety should be based on the specific characteristics of each individual product, not on the methods used to develop it. A subsequent report released by the NRC in April 2000 reiterated support for those earlier findings. Nevertheless, the United States and many foreign nations have developed regulatory systems that single out all gene-spliced products for uniformly heightened scrutiny, regardless of the level of risk individual products pose. This approach violates a primary principle of sound regulation: that the degree of scrutiny should be commensurate with risk.

The hidden peril of precaution

The adoption by so many nations of poorly conceived, discriminatory rules illustrates the perverse appeal of the status quo in decisions about safety and regulation. This tendency is captured in the intent of a relatively new risk avoidance philosophy, dubbed the "precautionary principle" by its advocates. Although a single standard statement of the supposed principle does not exist, its thrust is that regulatory measures should usually be taken to prevent or restrict an activity that raises conjectural threats of harm to human health or the environment, even when there is incomplete scientific evidence as to their magnitude or potential impacts. This is sometimes (misleadingly) represented as "erring on the side of safety." In practice, the precautionary principle is interpreted to mean that a product or technology should be assumed to be guilty until its innocence can be proven to a standard demanded by its critics, leaving much arbitrariness and a standard that can seldom be met.

Of course, caution has much to recommend it. Few would dispute that potential risks should be taken into consideration before proceeding with any new activity. In practice, however, the precautionary principle establishes a lopsided decisionmaking process that is inherently biased against change and therefore against innovation. Focusing mainly on the possibility that new products may pose theoretical risks, the precautionary principle ignores very real existing risks that could be mitigated or eliminated by those products. Elizabeth M. Whelan, president of the American Council on Science and Health, has aptly summed up the shortcomings of the precautionary principle. She observes that it always assumes worst-case scenarios, distracts consumers and policymakers from known and proven threats to human health, and ignores the fact that new regulations and restrictions may divert limited public health resources from genuine and far greater risks.

If the precautionary principle had been applied decades ago to innovations such as polio vaccines and antibiotics, regulators might have prevented occasionally serious, and sometimes fatal, side effects by delaying or denying approval of those products, but that precaution would have come at the expense of millions of lives lost to infectious diseases. One is also reminded of activists' persistent but ill-conceived opposition to fluoridation (and even chlorination!) of water and to vaccination against childhood diseases. These activities have risks, after all, and application of the precautionary principle would bias the regulatory system against not only taking them but even comparing them. Instead of demanding an assurance of safety that approaches absolute certainty, a more sensible goal would be to balance the risk of accepting new products too quickly against the risks of delaying or forgoing new technologies. Oblivious to such prudence, advocates continue pressing for precautionary regulation and have targeted recombinant DNA technologies for an array of burdensome new rules.

The implementation of regulations that discriminate against gene-spliced foods will stall agricultural progress and exact a substantial human toll.

Not satisfied with erecting national restrictions piecemeal, the environmental movement has increasingly focused its attention on international frameworks for regulation. The precautionary principle has already been inserted into such "soft" declarations as the 1990 Bergen Declaration and the 1992 Rio Declaration on Environment and Development as well as into more binding multilateral treaties, including the 1992 Convention on Biological Diversity and the 1992 Framework Convention on Climate Change. Thus also will the future of agricultural biotechnology be put in jeopardy by the stepwise progression of three international policies: the UN Industrial Development Organization's (UNIDO's) 1992 Code of Conduct for field trials, the Cartageña Protocol on Biosafety agreed to in January 2000 in Montreal, and the Codex Alimentarius Commission's deliberations on standards for biotech-derived foods.

One of recombinant DNA technology's great advantages is that, at least in theory, it became available almost immediately to those outside the industrialized world. Since it easily builds on traditional agriculture and microbiology to help improve regionally important crops, gene splicing could be an important element in increasing food production in developing countries. But because most developing nations had never enacted biotechnology-specific regulation--and the UN began to see such regulation as a growth industry--UNIDO drafted a Code of Conduct in 1992 as a framework to "provide help to governments in developing their own regulatory infrastructure and in establishing standards" for research on and use of organisms developed with recombinant DNA techniques.

This ill-conceived proposal describes regulatory requirements in the most stringent, unscientific, and self-serving terms. The document asserts that "[t]he UN is an obvious system through which to coordinate a worldwide effort to ensure that all [research and commercial applications of gene-spliced organisms are] preceded by an appropriate assessment of risks." But the code lacks even a rudimentary understanding of risk analysis, as it singles out all recombinant DNA­engineered organisms for heightened scrutiny but neglects conventionally produced organisms, even if they are known to pose risks.

The code requires the establishment of new environmental bureaucracies and demands that impoverished developing countries divert resources to regulate even small-scale field trials of obviously innocuous crops of local agronomic value, such as cassava, potatoes, rice, wheat, and ornamental flowers. By contrast, no oversight, no paperwork, and no bureaucracy are required for the testing of new variants of indigenous plants or microorganisms crafted with traditional techniques of genetic manipulation.

Nothing at all redeems these regulations or the "make-work" program they require. The worldwide scientific consensus on this point calls for the scope of oversight and the degree of scrutiny to be based on the risk-related characteristics of products, whether these products are living organisms or their inert by-products. The UNIDO drafters made a mockery of that pivotal point of scientific consensus as they forged ahead with a contradictory, expensive, and regressive regulatory system. In the process, they erected steep barriers to R&D, particularly for developing countries that aspire to meet some of their economic development and food security goals through gene splicing of locally or regionally important plants.

Burdensome national bureaucracies enforcing ill-conceived and excessive regulation will needlessly slow progress toward many of these goals. Agricultural biotechnology is particularly vulnerable, because although innovation is high, market incentives are often small and fragile. Vastly increased paperwork and costs for field testing will be potent disincentives to R&D in many countries. Such regulations remove an important tool of crop breeders: the ability to readily and rapidly test large numbers of new varieties in field trials. For example, each year an individual breeder of corn, soybean, wheat, or potato commonly tests in the field as many as 50,000 distinct new genetic variants. But overregulation of the type envisioned by the UNIDO Code of Conduct effectively prevents such intensive research.

The Biosafety Protocol

While UNIDO was aiming at boosting national regulation of biotechnology, another UN initiative, the Convention on Biological Diversity (CBD), began to target international regulation. A product of the 1992 UN Conference on Environment and Development, the CBD addresses a broad spectrum of issues related to the protection of biological diversity. Its stated intention, "the conservation of habitats in developing nations," is commendable. And the agreement's specific goals are crafted to sound universally appealing: identifying and monitoring components of biological diversity; adopting measures for ex situ conservation (that is, preserving seeds or sperm in repositories); and integrating genetic resource conservation considerations into national decisionmaking and adopting incentives for the conservation of biological resources. Although on the surface the goals appear unobjectionable, further inspection reveals that they are heavy on centralized planning and implementation, making them cumbersome and inflexible--not desirable characteristics in a piece of legislation intended to protect the most dynamic system on the planet. But whatever one's concerns about the convention, they pale in comparison to the liabilities of the Biosafety Protocol, developed under the mandate of the CBD.

The CBD required parties to establish their own national means to regulate what it calls Living Modified Organisms (LMOs): a neologism for plants, animals, and microorganisms developed with advanced biotechnologies. It also provided for, but did not require, the negotiation and adoption of a biosafety protocol regulating the "safe transfer, handling, and use of any [LMO] . . . that may have an adverse effect" on biological diversity. The parties pushed ahead, however, and formally began negotiating the protocol in 1993, even though a scientific panel established by the UN Environment Programme to review the need for such a protocol had advised that it would "divert scientific and administrative resources from higher priority needs" and "delay the diffusion of techniques beneficial to biological diversity, and essential to the progress of human health and sustainable agriculture."

After nearly seven years of negotiation, during which scientific considerations were conspicuously absent, the Cartageña Protocol on Biosafety was finalized and adopted at a meeting in Montreal in January 2000. Yet again, the parties agreed on a scheme that singles out recombinant DNA­engineered products for extraordinary regulatory scrutiny in spite of a total lack of evidence that such products deserve such special attention.

The goal of the UN's biosafety protocol is ostensibly to ensure that the development, handling, transport, field testing, and use of recombinant DNA-manipulated organisms in the environment are "undertaken in a manner that prevents or reduces the risks to biological diversity, taking also into account risks to human health." It was also hoped, by supporters of gene-splicing technology composing the Miami Group (a coalition of six major agricultural exporting countries), that a multilateral agreement would promote regulatory uniformity and predictability, so that the development of gene-spliced organisms could proceed. But even a cursory examination of the protocol shows that the agreement has less to do with legitimate concerns about public health and the environment and more to do with trade protectionism and pandering to antitechnology sentiments.

The primary regulatory mechanism of the Biosafety Protocol is the Advanced Informed Agreement (AIA), which requires the importing nation's government to approve or reject the first shipment of each new variety of LMO intended to be released into the environment. Governments can consider scientific, environmental, and even socioeconomic factors in their decisions. Under the protocol, the importing nation is given 270 days in which to make its decision, but there is no provision for the enforcement of this time limit, and the government's failure to respond does not imply consent.

Given U.S. dominance in gene splicing, foreign countries can practice protectionism under the cloak of environmentalism by creating barriers to gene-spliced products.

The essence of agricultural research is getting large numbers of experiments into field trials as rapidly and easily as possible, so one can imagine how a regulatory delay of nine months or more will adversely impede the transnational flow of improved seeds and other agricultural products. Yet, although the entire AIA process could have been opposed on principle, the Miami Group nations surrendered to the antibiotechnology movement on the issue of the AIA provisions and attempted only to carve out an exemption for their large agribusiness constituents. The Miami Group settled for an exemption from the burdensome AIA procedures for shipments of grains, fresh fruits and vegetables, and other harvested agricultural goods that are intended for use as food, animal feeds, or for processing. This alternative approval mechanism provides some protection for large shipments of commodity grains, the largest current source of LMO export, but does so at the expense of researchers wishing to export a broad spectrum of new varieties of crop plants, animals, and beneficial microorganisms for testing and use. Worse still, procedures and institutional mechanisms for ensuring compliance were left to be negotiated at a later date, even though the exact nature of these mechanisms is itself likely to be the subject of substantial debate.

Perhaps the primary point of contention will be resolving a precise legal definition for the precautionary principle language included within the Biosafety Protocol. The exact phraseology mentions a "precautionary approach," and uses the description of that term incorporated within both the Rio Declaration on Environment and Development and the CBD: "When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically." Debates on putting this concept into practice will doubtlessly revolve around measurements of "cost effectiveness," appropriate methods of risk analysis, and the acceptable resolution of intergovernmental disputes. But given the inability (or unwillingness) of precautionary principle advocates heretofore to settle on an exact definition of the obligations of regulators, with due recourse for deficiencies and defaults, proponents of sound science, legal certainty, and due process are likely to face an uphill battle.

One could easily question the wisdom of entering into an agreement that has so many unresolved issues. But with their special-interest AIA exemption secured, both the Miami Group governments and the biotechnology industry now claim, at least publicly, that the Biosafety Protocol establishes a uniform international framework under which they can operate and gives importing nations no more right to exclude biotech products than they had before completion of the agreement. Miami Group governments must now rely heavily on the General Agreement on Tariffs and Trade (GATT) and its World Trade Organization (WTO) to ensure free and open trade for gene-spliced commodity exports. One spokesman for the U.S. Biotechnology Industry Organization has argued that, regardless of what the Biosafety Protocol allows nations to do, under the WTO, international shipments of biotech goods may not be refused without a valid scientific demonstration of a true risk.

In general, this is a reasonably valid understanding of nations' rights and obligations under the WTO. The GATT/WTO Agreement on the Application of Sanitary and Phytosanitary Measures (SPS) ostensibly requires nations to introduce compelling scientific evidence in defense of their environmental and public health measures. But protectionism-minded regulators are unlikely to feel constrained by that legal obligation. For example, the European Union (EU) continues to resist a WTO decision overriding an EU ban on beef imported from the United States that was imposed because of concerns about artificial growth hormones. And as noted in a recent communication from the Commission of the European Communities on the precautionary principle, the WTO specifically gives countries leeway in enacting regulatory measures intended to protect the environment. Although WTO member nations are prohibited from discriminating against imported goods versus domestic goods, the GATT specifically allows WTO members to place environmental goals above their general obligation to promote trade. (Thus, given U.S. companies' dominance in gene splicing, foreign countries can effectively practice protectionism under the cloak of environmentalism.)

Given its recent history, it is not unlikely that the WTO will hold "precautionary" regulatory actions to be valid even when they do not meet the standards of scientific evidence otherwise demanded by the SPS, if those actions have been taken under the Biosafety Protocol. Conceivably, claims of adherence to the Biosafety Protocol could become a regulatory "safe harbor" in WTO jurisprudence; that is, as long as nations do not discriminate between the development or use of domestic versus imported gene-spliced products, they may then be free to prohibit importation of those products.

Ultimately, it is not clear that the WTO will overrule any but the most blatant abuses of precautionary regulation. Thus, rather than creating a uniform, predictable, and scientifically sound framework for effectively managing legitimate risks, the Biosafety Protocol establishes an ill-defined, unscientific, global regulatory process that permits overly risk-averse, incompetent, or corrupt regulators to hide behind the precautionary principle in delaying or deferring approvals.

The Codex Alimentarius

Not satisfied with this remaining uncertainty in how the WTO will handle its relationship to the Biosafety Protocol, the EU and environmental activists are trying to undermine the WTO more directly by writing the precautionary principle into the standards of the Codex Alimentarius Commission, the joint food standards program of the UN World Health Organization and Food and Agriculture Organization. In March of this year, Codex convened a Task Force on Foods Derived from Biotechnology specifically to address issues related to gene-spliced products. And at least two other Codex groups, the Committee on General Principles and the Committee on Food Labeling, are also reviewing rules specific to gene-spliced foods.

The prospect of poorly conceived, overly burdensome Codex standards for gene-spliced foods is ominous. Although parties to the Codex Alimentarius Commission are not directly bound by its principles, the WTO tends to defer to Codex principles for guidance on acceptable regulatory decisions, and members of the WTO will, in principle, be required to follow them. Jean Halloran, of the antibiotechnology group Consumers International, characterized Codex standards as a legal defense against WTO challenges to countries that arbitrarily stop trade in gene-spliced foods. "The Codex is important because of the WTO. If there is a Codex standard, one country cannot file a challenge [for unfair trade practices] against another country that is following the Codex standard. But when there is no Codex standard, countries can challenge each other on anything."

The first meeting of the Codex Task Force on Foods Derived from Biotechnology began auspiciously, with Thomas J. Billy, the temporary chairman of the Codex (and administrator of the U.S. Department of Agriculture's Food Safety and Inspection Service), noting the scientific consensus that biotech is a continuum of new and old technologies. He also stipulated that the risk-based characteristics of a new product (for example, changes in allergenicity or levels of endogenous toxins) are what are important for safety evaluations, regardless of the production techniques used.

Unfortunately, the group ignored Billy's scientific approach and moved deliberately toward circumscribing only food products made with gene splicing. Uncharacteristically, the U.S. delegation was part of the problem rather than the solution. Faced with such antagonism to the scientific consensus at such international meetings, the U.S. delegation commonly sets the tone by insisting on adherence to scientific principles and explaining the scientific basis for its own regulatory policy. This time, however, the United States could hardly insist on science-based regulation, having decided to surrender its own regulatory agenda to politics: Only a few weeks later, the U.S. FDA would announce a pending change in its own policy. (The U.S. delegation to the Codex committee is chaired by an FDA official.) Though the details of this new proposal won't be known until it is published late in 2000 or early in 2001, the agency has already announced that it will require all gene-spliced plants to undergo what amounts to a de facto premarket evaluation.

This impending deterioration in domestic regulatory policy tied the U.S. delegation's hands at the Codex meeting and will continue to do so in other international forums. As a result, Codex is en route to introducing various discriminatory and even bizarre requirements more appropriate to potentially dangerous prescription drugs or pesticides than to gene-spliced tomatoes, potatoes, and strawberries. Among the most egregious is a concept called "traceability": an array of technical, labeling, and record-keeping mechanisms to keep track of a plant "from dirt to dinner plate," so that consumers will know whom to sue if they get diarrhea from gene-spliced prunes. Here again, a once largely science-based organization has fallen prey to political machinations. The result will be to hobble research important for improving the productivity, and even the safety, of foods.

Precarious precautions

More than one billion people in the world now live on less than a dollar a day, and hundreds of millions are severely malnourished. By increasing the efficiency of agriculture and food production in myriad ways, recombinant DNA­engineered products can significantly increase the availability and nutritional value of foods and reduce their cost. But the application of the precautionary principle and the implementation of regulations that discriminate against gene-spliced foods will stall progress and exact a substantial human toll.

The unpredictability of "precautionary" regulation increases the financial risk of an already speculative endeavor. Although its proponents contend that the precautionary principle should not be used "as a disguised form of protectionism," there is no clearly defined evidentiary standard that could be used scientifically to satisfy demands for an assurance of "safety." Under its new standard of evidence, regulatory bodies can arbitrarily require any amount and kind of testing they wish. Consequently, claims of disguised protectionism are inherently difficult, if not impossible, to prove. Nor is there any procedural safeguard built into precautionary regulation that would serve to make such (barely) disguised protectionism less likely.

Ironically, many gene-spliced plants could also have tremendous environmental value, because they will require less synthetic pesticides and herbicides as well as less additional land devoted to farming. The UN itself has often cited increased cultivation of land for farming as the greatest challenge to biodiversity, and yet its regulatory initiatives will discourage the widespread application of some of the most promising techniques for enhancing agricultural productivity.

One wonders what the positive impacts would have been if, instead of imperiously anointing itself the world's biotechnology regulator, the UN had undertaken to explain to the world's opinion leaders and citizens the continuum between old and new biotechnology, the greater precision and predictability of the newer techniques, and the benefits that would accrue from overseeing the new biotechnology in a way that makes scientific and common sense.

Recommended reading

J. H. Adler, "More Sorry Than Safe: Assessing the Precautionary Principle and the Proposed International Biosafety Protocol," Texas International Law Journal 35 (2000): 173­205.

F. B. Cross, "Paradoxical Perils of the Precautionary Principle," Washington & Lee Law Review 53 (1996): 851­925.

H. I. Miller, Policy Controversy In Biotechnology: An Insider's View (Austin, Tex.: R. G. Landes Co., 1997).

H. I. Miller and G. Conko, "The Protocol's Illusionary Principle," Nature Biotechnology 18 (2000): 360­361.

J. Morris, ed., Rethinking Risk and the Precautionary Principle (London: Butterworth Heinemann, 2000).

National Academy of Sciences, Introduction of Recombinant DNA-Engineered Organisms into the Environment: Key Issues (Washington, D.C.: National Academy Press, 1987).

National Research Council, Field Testing Genetically Modified Organisms: Framework for Decisions (Washington, D.C.: National Academy Press, 1989).


Henry I. Miller, a senior research fellow at Stanford University's Hoover Institution, served as director of the FDA's Office of Biotechnology from 1989 to 1994. Gregory Conko is director of food safety policy with the Competitive Enterprise Institute in Washington, DC.