FEATURE When Does Similar Mean the Same: A Case for Relaxing Standards of Substantial Equivalence in Genetically Modified Food Crops Stephen L. Love1 University of Idaho, Aberdeen Research and Extension Center, Aberdeen, ID 83210-0530

Plant genetic engineering is rapidly mov- regulations have remained as strict or stricter present great possibilities for rapidly ing from theory to application. Transgenic than those initially adopted. improving the quantity and quality of food tomatoes (Lycopersicon esculentum Mill.), In the United States, three federal agencies available. The use of these techniques does potatoes (Solanum tuberosum L.), cotton are responsible for regulating genetically not result in food which is inherently less safe (Gossypium hirsutum L.), corn (Zea mays modified organisms, APHIS, EPA, and the than that produced by conventional means.” L.), soybeans [Glycine max (L.) Merrill], and Food and Drug Administration (FDA). The Assuming this is true, there should be little other crop plants are now being commer- role of APHIS, under the Plant Quarantine concern for the safety of foods derived from cially produced and sold. As useful genes are Act, is to ensure that modified organisms do genetically modified plants. However, identified and technical knowledge is ad- not become weedy or pestilent. The EPA caution is wise when utilizing any new tech- vanced, an expanding number of crop plants regulates only organisms that have pesticidal nology. For this reason, confirming food will be genetically modified. This technol- activity and assures environment safety with safety is a critical part of the science of ogy has the potential to help solve numerous respect to the specific pesticidal gene creating improved plant cultivars through production and marketing problems com- product. The FDA becomes involved if a biotechnology, especially in the early stages mon to horticultural crops. Unfortunately, modified organism is to be used as food and of consumer acceptance. However, certain the high cost of developing genetically engi- oversees all food safety issues. It is respon- elements of the current use of the substantial neered cultivars may limit the use of this sible for determining that foods from geneti- equivalence concept add extensive develop- technology in minor-use horticultural crops. cally modified crops are both safe and nutri- mental costs to genetically modified food These costs come from numerous develop- tionally adequate. In Canada, Health and crops. The present interpretation of substan- mental activities, including basic genetic re- Welfare Canada is responsible for regulating tial equivalence dictates that the level of any search, field testing, meeting regulatory re- all aspects of genetically modified organisms measurable constituent in a genetically quirements, marketing, and public relations destined for food use. Agriculture Canada modified cultivar must be similar or equal to work. Improving almost any crop is techni- regulates organisms associated with that in the cultivar from which it was derived. cally possible; however, unless these costs agriculture that are not destined for food use. Under this definition, there is no limit to the are minimized, neither private companies This paper discusses a concept known as number of constituents that must be mea- nor publicly funded research programs will substantial equivalence as it relates to safety sured. For any crop the number that could be be able to afford to use these genetic ad- and nutrition, and consequently, includes the considered nutritionally and toxicologically vances for improvement of most horticul- areas of regulation that fall under the juris- important is immense. If plants from every tural crops. Thus, this technology will not diction of FDA and Health and Welfare transformation event must be analyzed for help the majority of horticultural producers Canada. every imaginable constituent, using samples solve problems and meet increasingly strin- Substantial equivalence is the concept es- from multiple sites and years, developmental gent environmental policies. tablished by a joint committee of the Food costs will skyrocket. For this reason, a bal- Meeting federally mandated regulations and Agricultural Organization (FAO) and ance must be struck between ensuring food for food and environmental safety is one of World Health Organization (WHO) and safety and holding costs to a level that allows the major costs of developing genetically adopted by regulatory agencies in the United this technology to add to food availability. modified cultivars. The content of these regu- States and Canada, as well as in Europe, as a The immediate need is to answer two impor- lations is still in a state of flux. In the future, guide to assess the safety status of food crops tant questions about establishing substantial they may become more stringent, or may be developed via biotechnology (FAO/WHO, equivalence: 1) What is the appropriate modified, or even removed, as definitive data 1991). In current practice, establishing comparative standard within a crop? 2) What and experience show safety issues to be of substantial equivalence involves confirma- are the critical constituents to be analyzed for little or no concern to the public. This latter tion that nutritional composition (meaning any given crop? trend is already occurring with respect to natural toxicants and nutritional components) I believe that the concept of substantial field testing and production. Over the past of genetically modified food crops is similar equivalence is an appropriate one for several years, field testing has become much to or identical with that of the original, unal- evaluating genetically modified crop plants, simpler as the U.S. Dept. of Agriculture/ tered crops from which they were derived. if substantial equivalence is appropriately Animal and Plant Health Inspection Service Because introduction of cultivars of defined. Establishing substantial equivalence (APHIS) and the Environmental Protection genetically modified crops into the food chain for specific prioritized constituents of Agency (EPA) have relaxed standards for is a recent phenomenon, procedures to be genetically modified cultivars is important. handling genetically engineered plant used in establishing substantial equivalence For each crop these critical constituents will materials. However, food safety-related are still being developed. This evolution differ. The thesis of this paper is that ap- includes both identification of acceptable plication of standards for establishing comparatives and generation of lists of key substantial equivalence should be similar to Received for publication 23 July 1999. Accepted compositional constituents. guidelines historically used in traditional for publication 22 Nov. 1999. Manuscript number A 1991 FAO/WHO report states that, breeding and that a limited number of impor- 99717 of the Idaho Agricultural Experiment Station. “Biotechnology has a long history of use in tant constituents can be predetermined for The cost of publishing this paper was defrayed in part by the payment of page charges. Under postal food production and processing. It represents most crops. Having had considerable experi- regulations, this paper therefore must be hereby a continuum embracing both traditional ence with potatoes, I will use this crop as an advertisement solely to indicate this fact. breeding techniques and the latest techniques example, to illustrate the principles I feel 1Research Professor. E-mail address: slove@ based on molecular biology. The newer bio- should dictate the determination of substan- uidaho.edu technological techniques, in particular, tial equivalence.

HORTSCIENCE, VOL. 35(5), AUGUST 2000 803 FEATURE

EARLY PROCEDURAL as part of the definition of substantial equiva- The range of variability for these same PRECEDENCE lence will provide some flexibility in the constituents among genetically modified po- process of cultivar improvement through bio- tatoes derived from a single cultivar falls Early efforts to establish substantial technology, with little or no change in the within much narrower confines. This is dem- equivalence for genetically modified pota- nutritional value of the overall potato food onstrated by a summary of 1992 trials with toes were closely scrutinized by both re- crop. ‘Russet Burbank’ derived clones transformed search groups and regulatory agencies. Con- A review of 257 release documents for with a Bacillus thuringensis gene (Table 2). sequently, evaluations were thorough and North American potato cultivars revealed There were slight differences among the included over 20 biochemical constituents very little reliance on nutritional constituents clones for several constituents, probably (Lavrik and Love, 1994). Also, only the origi- as selection criteria or as a basis for release because of insertion effects, somaclonal varia- nal cultivar from which the genetically modi- (see references cited in Chase, 1992). There tion, or unknown causes, but the range was fied cultivars were derived was used for are two exceptions. One is for a group of very narrow when compared to that for comparison. Constituents compared included compounds called glycoalkaloids, natural genetically dissimilar cultivars. not only nutritional and toxicological com- toxicants with known mammalian toxicity Historical precedence from past cultivar ponents, but also agronomic characteristics for which a voluntary ceiling has been estab- development work tends to support using and measures of processing quality. Compo- lished (Sinden, 1991). Glycoalkaloid con- varietal range for substantial equivalence sitional constituents analyzed in these early centration was documented in 31% of the comparisons rather than equivalence within studies included total solids, glycoalkaloids, total release documents and in nearly all a single cultivar. This precedent lends cre- sugars, proteins, vitamin C, fats, ash, dietary documents published since 1973. The second dence to a broader definition for the concept fiber, thiamine, pyridoxine, folic acid, nia- constituent is total tuber solids, measured as of substantial equivalence. However, there is cin, riboflavin, calcium, copper, iron, iodine, tuber dry matter or estimated from measure- one argument for requiring an original culti- magnesium, phosphorus, potassium, sodium, ment of tuber specific gravity. Total solids is var and its genetically modified counterparts and zinc. This early work set a precedent for an important quality factor and the most to be virtually identical for some constitu- subsequent procedures and resulted in ex- important determinant of culinary appeal in ents. The compositional nature of each po- pectations by regulatory agencies that each potatoes (Murphy et al., 1967). Dry matter tato cultivar determines its usefulness for the genetically modified cultivar be exactly equal content is documented in nearly all release preparation of specific in-home or industri- to its original counterpart for all of these documents published since 1958 and in many ally processed food products. Within the po- constituents. This resulted in a situation as early as 1935 (see references cited in tato industry, lists are maintained of cultivars wherein requirements, with respect to the Chase, 1992). acceptable for certain products (Talburt, definition of equivalence, are above what Information on only four other nutritional 1975). If a genetically modified cultivar is may actually be necessary given the FAO/ constituents has been published in release substantially different from its original coun- WHO guidelines for establishing substantial documents of traditionally bred cultivars, terpart, but is sold under the same name, equivalence. These guidelines state, “The despite the fact that a much longer list is difficulties may arise for consumers or some product to be assessed is the food plant and, required on consumer packages (Pennington segments of the potato industry. For pota- more specifically, those parts of it that will be and Wilkening, 1997). These are reducing toes, the constituents for which changes are consumed. The standard used for purposes of sugars (glucose and fructose), sucrose, pro- most likely to create problems (because they comparison must be the traditional plant or tein, and vitamin C, and were listed in less are critical components of product quality) food.” (FAO/WHO, 1991). With regard to than 3% of release documents. In each case, are total solids and reducing sugar content. potatoes, the “traditional plant or food” is an this information was included as part of the aggregate of hundreds of traditionally bred cultivar description, not as evidence of value IMPORTANT NUTRITIONAL AND cultivars. If this is considered, using as the or acceptability. BIOCHEMICAL CONSTITUENTS only acceptable comparison equivalence to Within each constituent, concentrations the original cultivar is more stringent than is published in release documents varied widely The FAO/WHO guidelines for safety as- dictated by the above guidelines. Also, pota- among cultivars (Table 1) (see references sessment of genetically modified cultivars toes are not an important source of many of cited in Chase, 1992). The natural variability contain recommendations that compositional the constituents currently being measured, was even greater among potato breeding analyses focus on constituents that are of meaning small changes in content will not clones that we have evaluated at the Univ. of major nutritional importance. A quote from meaningfully alter the quality of the overall Idaho since 1978 for the Western Regional the guidelines reads, “Whenever changes are food supply. Coordinating Committee (WCC-27), a group made in the process by which a food is made of potato breeders in the western United or a new process is introduced, the implica- CONCEPT OF EQUIVALENCE IN States (Table 1). Breeders consider this tions for the safety of the product should be TRADITIONAL BREEDING variability to be normal, natural, and examined. The scope of the examination will acceptable. depend on the nature of the perceived con- Almost 200 potato cultivars are currently produced and sold in the United States, Canada, and Europe. They vary for any given Table 1. Ranges of concentrations of nutritional and toxicological constituents of potato cultivars as trait, including concentrations of nutritional published in release documents and as evaluated for the Western Regional Coordinating Committee constituents and natural toxicants. This vari- (WRCC-27) from 1978–1997. ability has been largely ignored by breeders, z y entirely ignored by consumers and regula- Release Documents WRCC-27 Data tory agencies, and is considered normal for Constituent Minimum Maximum Minimum Maximum –1 x the species. Thus, the standard for accept- Glycoalkaloids (mg·kg FWB) 5.0 180.0 4.0 432.0 ability in traditionally bred cultivars is much Total solids (%) 15.5 26.1 15.2 27.2 Reducing sugars (% DWB)w 0.10 1.20 0.01 1.70 looser than for those derived from biotech- Sucrose (% DWB)w 0.31 0.71 0.11 1.20 nology. Thus, genetically modified cultivars, Protein (% DWB)w 6.3 9.6 2.5 10.0 having concentrations of key constituents Vitamin C (mg·kg–1 FWB)x 149.0 350.0 100.0 329.0 that are within the range expressed by these zDerived from potato release documents listed in Chase, 1992. commercially produced cultivars (rather than yTaken from reports of the Western Regional Potato Variety Trials, 1978–97, Aberdeen Research and being identical to the cultivar from which Extension Center, Univ. of Idaho, Aberdeen. they originate) should be considered sub- xFWB indicates measurements made on a fresh-weight basis. stantially equivalent. Adopting this concept wDWB indicates measurements made on a dry-weight basis.

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