THE FAILINGS OF THE PRINCIPLE OF SUBSTANTIAL EQUIVALENCE IN REGULATING
John Fagan, Ph.D., Professor of Molecular Biology, Maharishi University of Management
The concept of substantial equivalence has been used in Europe, North America, and elsewhere around the world as the basis of regulations designed to facilitate the rapid commercialization of genetically engineered foods. For instance, European Commission (EC) regulations concerning novel foods and food ingredients apply the concept of substantial equivalence to both the safety testing and to the labeling of genetically engineered foods. Genetically engineered foods classified as substantially equivalent are spared from extensive safety testing on the assumption that they are no more dangerous than the corresponding non-genetically engineered food (1). Using similar arguments, genetically engineered foods classified as substantially equivalent are not required to be labeled as genetically engineered (2). The effect of these regulations has been to allow genetically engineered foods to enter the market place without sufficient testing to assure safety and without sufficient labeling to allow consumers to decide for themselves whether or not to purchase and eat these novel foods. The health of the population of Europe is thus being placed at risk.
The fundamental inadequacies of this approach have been discussed
previously. For instance, one article presented in the Proceedings of the
Organization for Economic Cooperation and Development (OECD) Workshop on
Food Safety Evaluation (3), came to the following conclusions:
(1) Because the concept of substantial equivalence has no dimensions, it cannot be used as a predictor of which novel foods will require substantial safety testing in animals.
(2) Depending on the nature of the novel food, the usefulness of the concept of substantial equivalence in determining the necessity for extensive safety testing ranges from useful to negligible.
(3) The number and range of safety tests required is best determined, not by the concept of substantial equivalence, but by the nature of the product under consideration.
At first glance the term substantially equivalent implies that two foods are equivalent in all characteristics that are of importance to the consumer-safety, nutrition, flavor, and texture. However, in actual practice the investigator compares only selected characteristics of the genetically engineered food to those of its non-genetically engineered counterpart. If that relatively restricted set of characteristics is not found to be significantly different in these two, the genetically engineered food is classified as substantially equivalent to the corresponding non-genetically engineered food and is required to be neither tested further nor labeled as genetically engineered.
The argument supporting this practice is that since most of the characteristics of a particular genetically engineered food are similar to those of its non-genetically engineered counterpart, it must be the case that the genetically engineered food is substantially equivalent to its non-genetically engineered counterpart with respect to all characteristics relevant to the consumer. This is obviously a fallacious argument, and should not be used as the basis for avoiding more extensive testing and for avoiding the labeling of genetically engineered foods. Most critically, if characteristics important to food safety are not evaluated directly, the safety of consumers will be in jeopardy.
Any claim of substantial equivalence is only as good as the series of tests upon which that claim is based. In practical terms, if a genetically engineered food is different from its non-genetically engineered counterpart, that difference will be detected only if a test is carried out that is capable of measuring the specific characteristic which is different between the two. Therefore, if the tests prescribed for determining substantial equivalence do not include one or more tests capable of quantitating the characteristic which happens to be different in the genetically engineered food compared to its non-genetically engineered counterpart, the genetically engineered food will be wrongly classified as substantially equivalent to its non-genetically engineered counterpart.
Currently, the testing procedures required in Europe, North America and elsewhere consist almost exclusively of specific chemical and biochemical analytical procedures designed to quantitate a specific nutrient or a specific toxin or allergen. These tests focus on specific components of a food that are suspected to be altered in that particular genetically engineered food, based on the known characteristics of its non-genetically engineered counterpart, and based on the known characteristics of the genes introduced into that organism. For instance, in its assessment of Roundup Ready soybeans, Monsanto quantitated a few of the allergenic proteins known to be normally produced in soybeans, showing that genetic manipulations had not accidentally caused Roundup Ready soybeans to produce higher than normal levels of those allergens.
Important as these studies are, however, they fail to even begin to assess one very substantial class of risks that are inherent in genetically engineered foods. That class of risks consists of health hazards resulting from the unanticipated side-effects of genetic engineering. Such testing schemes are completely incapable of detecting unsuspected or unanticipated health risks that are generated by the process of genetic engineering, itself.
It is a scientific fact that the process of genetic engineering often gives rise to unanticipated side-effects. These can-and have been shown to-introduce unforeseen allergens and toxins into foods and unexpectedly reduce nutritional value. Not every genetically engineered food will have these problems, but there is a finite probability that any given genetic modification will lead to unanticipated side-effects that result in food characteristics that threaten the health of consumers.
For instance, in 1989 Showa Denko K.K. marketed tryptophan that had been produced in genetically engineered bacteria as a nutritional supplement in the USA. When this product was placed on the market, it made thousands of consumers ill. Of these, 1500 were permanently disabled and 37 died. Analysis by high pressure liquid chromatography indicated that this product was more than 99.6% pure tryptophan. However, these also contained traces of a highly toxic contaminant. This toxin accounted for less than 0.01% of the total mass of the product but this was sufficient to seriously threaten health.
According to the measurements made, the genetically engineered tryptophan was equal in purity, and thus substantially equivalent, to previous preparations that had been produced using natural bacteria. However it was clearly not substantially equivalent with regard to human safety. If other tests had been required, such as animal or human feeding tests, which are capable of screening broadly for harmful substances, the fact that this material was not substantially equivalent would have been obvious. However, those tests were not done.
Health Risks in Derivatives
Another example of how the concept of substantial equivalence can lead to abuses is the claim that is commonly made that corn oil from genetically engineered corn need not be labeled as genetically engineered because the process of oil production separates the oil from all potentially toxic or allergenic constituents of corn and that the composition of the oil itself is identical to that obtained from non-genetically engineered corn. Similar arguments have been used to justify the deregulation of oil from genetically engineered soybeans.
The problems with these arguments are two: First, corn oil is not chemically pure. It is well known that corn oil still contains sufficient corn proteins to elicit allergic reactions in individuals who are highly allergic to corn. Therefore it is highly likely that it will also contain small amounts of the genetically engineered proteins present in genetically engineered corn. An individual who is allergic to these proteins would be likely to react negatively to oil derived from genetically engineered corn. Second, only the major constituents of genetically engineered corn oil have been examined in assessing substantial equivalence. However, some of the minor constituents of this oil, which were ignored in this assessment, could be of substantial significance to the nutritional value or the safety of this product. For instance, genetic manipulations could unexpectedly alter oil metabolism by a number of mechanisms, generating a toxic fatty acid derivative. Thus, this claim of substantial equivalence is superficial and should not be used as an argument to justify avoidance of further testing and labeling.
Clinical Tests Needed
Given that genetic engineering can introduce unexpected health hazards into foods, it is logical that every genetically engineered food should be subjected to tests that are capable of detecting a wide range of unforeseen health threats. Yet, at present, the liberal use of the concept of substantial equivalence makes it possible to avoid such testing.
What additional tests are required? Tests are needed that are capable of screening for a wide range of diverse allergens and toxins. It is not possible within the scope of this document to discuss in detail the deficiencies in the current system and the measures required to rectify this situation. (This subject is discussed in Assessing the Safety of Genetically Engineered Foods, a Science-Based, Precautionary Approach, by the author) In short, what is missing in current testing programs is clinical tests in which humans are fed the genetically engineered food in question both short-term and long-term.
Human tests are of primary importance because animals are poor models for assessing the human health impacts of foods. In particular, animal tests provide virtually no useful information regarding the allergenicity of food to humans.
Only clinical tests have the broad specificity and relevance to human physiology needed to detect the wide range of allergens and toxins that might result from unexpected side-effects of the genetic engineering process. Without such tests, the full range of allergens and toxins that can be introduced via the process of genetic engineering cannot be detected, and without such tests, it is impossible to assure that a given genetically engineered food is in fact free from health-damaging characteristics.
Need for Labeling
Even if more stringent testing is implemented, it is essential that genetically engineered foods be labeled as genetically engineered. No testing scheme can ever be exhaustive. Therefore some residual risk of undetected health damaging characteristics will always remain with foods that have been produced using a technique, such as genetic engineering, that is capable of introducing into a food a wide range of unexpected side effects. For instance, if clinical experiments are carried out for 3 years, longer term health effects may be overlooked that take 5 or 10 years to manifest. Invariably, residual risk remains regardless of the tests carried out and regardless of the testing period chosen. Labeling these foods as genetically engineered allows consumers to choose for themselves whether or not to accept this residual risk.
Industry has stiffly opposed proposals that would have required genetically engineered foods to undergo clinical testing similar to that which is standard for novel food additives. The expense and time required for testing is perceived as a hindrance to commercialization of genetically engineered foods. However, in the long run, more rigorous testing will be good, not only for consumers, but also for industry.
Without such testing some genetically engineered foods that seriously damage the health of consumers will enter the market. Thus, this short-sighted approach to safety assessment clearly favors commercial interests while placing the health of the entire population at risk. Not only does this abrogate scientific responsibility and basic humanitarian values, but it is also bad business, because it will inevitably lead to loss of consumer confidence in genetically engineered foods.
1. Regulation EC /95 of the European Parliament and of the Council Concerning Novel Foods and Food Ingredients, Article 3.4.
2. Regulation EC /95 of the European Parliament and of the Council Concerning Novel Foods and Food Ingredients, Article 8.1.
3. OECD, DSTI/STP (95)18, Paris, 1995, pages 79-87.
4. Does Medical Mystery Threaten Biotech? Science, P age 619, 2 November 1990
5. An Investigation of the Cause of the Eosinophilia-Myalgia Syndrome Associated with Tryptophan Use, New England Journal of Medicine, 323: 357-365, 1990.
6. EMS and Tryptophan Production: A Cautionary Tale, TIBTECH, 12:346-352, 1994.
John B. Fagan, Ph.D. Professor of Molecular Biology Maharishi University of Management (Maharishi International University 1971 to 1995) 1000 North Fourth Street Fairfield, Iowa, 52557-1078 Phone(515) 472-8342 Fax (515) 472-5725 email email@example.com