IV. Current Regulation of GE/NBTs in Agriculture

Thirty years ago, the White House published an overarching regulatory regime for agriculture research and products, the 1986 U.S. Coordinated Framework for the Regulation of Biotechnology (CF), which relied on existing laws to regulate GE products.

In a Faustian bargain to placate hostile politicians, please eager regulators, calm anxious industry, and protect worried consumer activists, the White House announced a risk-based regulatory framework that focused on the particular risk a biotechnology product might present, rather than on the genetic modification technique used to develop it. However, agency interpretations and implementation mainly ignored this risk-based guidance, and instead imposed a regulatory approach that required premarketing and even pre-field-testing review of new GE organisms. The rigorous and often dilatory case-by-case reviews constituted a level of scrutiny far in excess of what would be required for the same product achieved through less precise methods of conventional non-molecular modification.

The regulations (or guidances) actually implemented under the Coordinated Framework incorrectly claimed to be product-focused and risk-based, but are, in fact, process-based because they are in most cases triggered by the use of virtually any r-DNA modification, regardless of the existence of a demonstrable hazard. The USDA, EPA, and FDA are the principal agencies regulating GE crops, pesticides, herbicides, drugs, foods and animals. They address the products’ hypothetical hazards to agriculture, the environment, and/or human and animal health. Thus, for example, depending on the crop and trait, one, two, or all three of these agencies may independently evaluate and regulate an agricultural product. In many cases, all of the reviews are arguably superfluous, creating uncertainty and significant expense for product developers.

In addition to the product-specific reviews, the National Environmental Policy Act (NEPA) requires that an environmental assessment or environmental impact statement be prepared for any “major federal action” that may have a significant impact on the “human environment.” Accordingly, a GE product review requires yet another separate review to comply with NEPA, except for evaluations performed by the EPA, whose reviews are considered to be equivalent to those required under NEPA.

U.S. Department of Agriculture

The Department of Agriculture (USDA), through its Animal and Plant Health Inspection Service (APHIS), is responsible for the regulation of genetically engineered plants. The Plant Protection Act (formerly the Plant Pest Act) has long regulated the importation and interstate movement of listed organisms (plants, bacteria, fungi, viruses, etc.) that are plant pests. A plant that an investigator might wish to introduce into the field is either on the prohibited list of plant pests, and therefore requires a permit, or it is not regulated.

For the regulation of r-DNA modified plants, APHIS extended the original concept of a plant pest (something known to be harmful) and invented a new category — “regulated article” — specifically defined as a potential plant pest to capture virtually every r-DNA-modified plant for case-by-case review, regardless of its potential risk.

In order to perform a field trial with a regulated article, a researcher must apply to APHIS and submit extensive paperwork before, during, and after the field trial. After conducting field trials for a number of years at many sites, the researcher must then submit a vast amount of data to APHIS and request “deregulation,” which is equivalent to approval for unconditional release and sale. These requirements make genetically engineered plants extraordinarily expensive to develop and test. The cost of discovery, development, and regulatory authorization of a new trait introduced between 2008 and 2012 averaged $136 million (about a quarter of which were regulatory compliance costs), according to Wendelyn Jones of DuPont Pioneer, a major corporation involved in crop genetics.

APHIS’s regulatory approach to r-DNA-modified plants is difficult to justify. Plants have long been selected by nature, as well as bred or otherwise manipulated by humans, for enhanced resistance or tolerance to external threats to their survival and productivity, such as insects, disease organisms, weeds, herbicides, and environmental stresses. Plants have also been modified for qualities attractive to consumers, such as seedless watermelons and grapes and the tangelo, a tangerine-grapefruit hybrid.

For new varieties of plants, risk is a function of certain characteristics of the parental plant (such as weediness, toxicity, or ability to “outcross” with other plants) and of the introduced or modified gene or genes. In other words, it is not the source or the method used to introduce a gene but its function that determines how it contributes to risk. Plant breeders conduct assessment of the risks and determine the approach to managing the new varieties. New varieties of plants (whichever techniques are used to craft them) that normally harbor relatively high levels of various toxins are analyzed carefully to ensure that levels of those substances remain in the safe range. Celery, squash, and potatoes are among the crops in need of such attention.

Under USDA’s APHIS, however, it is primarily plants made with the newest, most precise techniques that are subjected to more extensive and burdensome regulation, independent of the level of risk. Thus, the concept of “regulated article” turns on its head the common-sense notion that the degree of safety regulation — i.e., government intrusion — should be commensurate with the risk of a product, process or activity.

The regulated article construct, which is based on the possibility that the presence of part of a regulated plant pathogen could confer plant pest risk on the GE plant, is bureaucratically contrived and scientifically baseless. It leads to incongruous results. For instance, plant transformation involving synthetic or non-pathogen-derived DNA introduced by a different technique such as biolistics is not subject to regulatory consideration by APHIS. In contrast, an identical product created using a process involving the plant pathogen Agrobacterium or the S35 promoter from Cauliflower Mosaic Virus becomes a “regulated article,” while as a practical matter none of these should be subject automatically to case-by-case review.

APHIS has advised that NBTs do not trigger oversight by APHIS because the agency lacks the statutory authority under the Plant Protection Act to regulate if the resultant organism does not contain DNA from a plant pest.

Food and Drug Administration

Since 1992 the Food and Drug Administration (FDA) has had a science- and risk-based approach toward “novel foods” made with any technology. FDA’s Center for Food Safety and Nutrition does not impose discriminatory regulation based on the use of one technique or another, but conducts a more extensive review if, for example, the food contains a substance completely new to the food supply, has increased levels of a toxin, or would expose consumers to an unexpected allergen. In addition, FDA has resisted calls for mandatory labeling of genetically engineered foods as not materially relevant information under the federal Food, Drug and Cosmetic Act, and as not consistent with the statutory requirement that food labeling must be accurate and not misleading.

In implementing its policy, FDA created a Plant Biotechnology Consultation Program to work cooperatively with developers of GE plants to help them ensure foods made from their new GE plant varieties are safe and lawful. In this program, FDA evaluates the safety of food from the new GE crop before it enters the market. While established as a voluntary program, GE plant developers routinely participate with FDA to consider food safety and nutritional issues, such as whether the GE plant contains a new toxin or allergen or is as nutritious as its traditionally bred counterpart.

FDA has asserted regulatory jurisdiction over GE animals, taking advantage of a perceived regulatory vacuum. In 2008 the FDA’s Center for Veterinary Medicine issued guidance that said that the altered DNA within every genetically engineered animal would be evaluated as a veterinary drug and subjected to the same onerous premarket approval procedures and regulations as drugs (such as pain relievers and anti-flea medicines used to treat animals). The rationale offered was that a genetically engineered construct “that is in a [GE] animal and is intended to affect the animal’s structure or function meets the definition of an animal drug.”

The failure of this approach is obvious from FDA’s taking more than 20 years to complete a review of a faster-growing a GE salmon made by a company that first approached FDA in 1993. Today neither that salmon, nor any other GE food animal is marketed in the U.S. Although the FDA finally approved the GE salmon in 2015, Congress has prohibited its sale until such time that guidelines for its labeling are finalized. In contrast, the GE salmon has been approved in Canada and is popular among consumers there.

FDA similarly struggled for a protracted time to approve a limited field trial of a GE mosquito which was designed to reduce the population of these disease-carrying insects. Eventually FDA had to defer to EPA’s broad authority over pesticides and transferred jurisdiction to that more suitable agency.

The once-promising sector of GE food animals in the U.S. has virtually disappeared. They were first developed 30 years ago in land-grant university laboratories, but those animal-science innovators have grown old without gaining a single approval for their work. Many academic researchers who have introduced promising traits into animals have moved their research to other nations, particularly Brazil. Many younger animal scientists have simply abandoned the field. As for the faster-growing salmon, regulators kept it in regulatory limbo while imposing costs of more than $75 million on its developers. Genetically engineered animals could be regulated elsewhere and under different paradigms at far less time and cost.

There is reason to worry that the use of “new breeding techniques,” or NBTs, may not fare any better at FDA than the salmon. For example, a University of Minnesota animal scientist has used the TALENs technique to edit a gene in the Holstein dairy cattle breed to duplicate the DNA sequence of the hornless (polled) gene found in the Angus beef cattle breed. This gene editing results in Holstein cattle which exhibit the hornless trait, a modification that provides greater animal welfare for dairy cattle (i.e., by making mechanical dehorning unnecessary) and greater safety for dairy farmers (i.e., avoidance of being gored). But FDA has refused to consider the Holsteins under the same approach it uses for GE foods. Rather, FDA has asserted that the Holstein cattle contain a “new animal drug” and that, therefore, the animals cannot be released or marketed until a new animal drug approval is granted.

Environmental Protection Agency

The EPA regulates field tests and the commercial use of pesticides under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). In 2001, the agency issued final rules for the regulation of GE plants and created a new concept, “plant-incorporated protectants” (PIPs), defined as “pesticidal substances produced and used by living plants,” but EPA regulation captures such pest-resistant plants only if the “protectant” has been introduced or enhanced by the most precise and predictable GE techniques.

Extensive testing is required for registration of these new “pesticides,” including gathering copious data on the parental plant, the genetic construction, and the behavior of the test plant and its interaction with various species, among other factors. (These requirements could not be met for any plant with enhanced pest-resistance modified with older, cruder techniques, which are exempt from the FIFRA rules.) While FIFRA provides a 10-acre research exemption for pesticides, it does not apply to PIPs.

The EPA conducts repeated, redundant case-by-case reviews: before the initial trial, when trials are scaled up or tested on additional sites, and again if even minor changes have been made in the plant’s genetic construct. The agency repeats that review again at commercial scale. The agency’s classification of living plants as pesticides, even though the regulatory term is “plant-incorporated protectants,” has been vigorously and widely condemned by the scientific community for decades.

The assessment of genetically engineered crops within the EPA is intended to regulate the pesticidal property rather than the crop itself. For instance, a GE Bt-containing crop is evaluated principally through assessment of the PIP (the expressed Bt protein), provided the transformed crop otherwise shows similarity (in weediness and outcrossing potential) to its non-transformed counterpart. But the newly-introduced pesticidal trait and the plant itself are indivisible.

EPA’s classification of fragments of DNA, nucleotides, and genes as pesticides has created its own set of incongruities. In contrast to crops created by conventional breeding, in which the genetic basis for the new traits is often complex and uncharacterized (because the techniques employed are less refined), GE crops (in which the genetic changes are more circumscribed) with new or enhanced pesticidal properties must be reregistered as pesticides at periodic intervals, and the seed or nursery stock must bear a pesticide label. Fines have been imposed on companies importing seeds from winter nurseries when they have not had the proper pesticide import permits.

Not surprisingly, only three crops engineered for disease resistance — papaya, plum and potato — have managed to receive EPA approval, in spite of the ease with which resistance genes can be transferred or edited. In contrast, the multitude of disease-resistant crops developed using traditional breeding methods faced no premarket regulatory review.

As to NBTs, under FIFRA there is an exemption for “pesticidal substances produced through conventional breeding of sexually compatible plants,” so a lot depends on whether or not CRISPR-cas9 is considered conventional breeding by the EPA. The agency has not yet made a decision.

The Toxic Substances Control Act (TSCA) regulates chemicals other than pesticides. GE microorganisms are “new chemicals” subject to pre-market approval for testing and commercial release. Captured for review is any “new” organism that contains combinations of DNA from sources that are not closely related phylogenetically. As molecular genetic engineering techniques can easily create new gene combinations with DNA from disparate sources, EPA concludes that these combinations therefore “have the greatest potential to pose risks to people or the environment,” according to the agency press release that accompanied the rule.

From a risk perspective, EPA’s statement is a non sequitur. The particular genetic technique employed to construct new strains is irrelevant to risk, as is the origin of a snippet of DNA that may be moved from one organism to another. What matters is its function. Scientific principles and common sense dictate the questions that are central to risk analysis for any new organism. How hazardous is the original organism from which DNA was taken? Is it a harmless, ubiquitous organism found in garden soil, or one that causes illness in humans or animals? Does the newly transferred genetic material code for a potent toxin? Does the genetic change merely make the organism able to degrade oil more efficiently, or does it have other effects, such as making it more resistant to being killed by antibiotics or sunlight?

NBTs have created concern at EPA, where there are internal pressures to declare that all forms of molecular modification create “new chemicals,” which would still further expand the agency’s regulatory reach under TSCA. If EPA were to adopt this broader “new chemicals” approach, there is legitimate concern that products from these new techniques would face the same fate as r-DNA-modified microorganisms, only one of which has been approved by EPA since it declared them to be new chemicals in 1997.