Henry Miller | October 8, 1999
In their paper1 criticizing "substantial equivalence" applied to foods from recombinant organisms, Millstone et al appear to misunderstand the term. (Read the article as is appeared in Nature magazine.)
They also appear to be unaware of the extant regulatory standards for new foods generally, and of the experience with and the scientific consensus about assessing the safety of products derived through recombinant DNA techniques.
The history of the term "substantial equivalence," first applied to food by work at OECD, is important. In 1986, the OECD's Group of National Experts on Biotechnology reached a consensus that: "While rDNA techniques may result in the production of organisms expressing a combination of traits that are not observed in nature, genetic changes from rDNA techniques will often have inherently greater predictability compared to traditional techniques, because of the greater precision that the rDNA technique affords"; and "It is expected that any risks associated with applications of rDNA organisms may be assessed in generally the same way as those associated with non-rDNA organisms."2
Others echoed this consensus. In 1992, Nature editorialized that "the same physical and biological laws govern the response of organisms modified by modern molecular and cellular methods and those produced by classical methods ... [Therefore] no conceptual distinction exists between genetic modification of plants and microorganisms by classical methods or by molecular techniques that modify DNA and transfer genes."3
The OECD's experts group subsequently took up food safety specifically, concluding in a 1993 report that: "Modern biotechnology broadens the scope of the genetic changes that can be made in food organisms, and broadens the scope of possible sources of foods. This does not inherently lead to foods that are less safe than those developed by conventional techniques. Therefore, evaluation of foods and food components obtained from organisms developed by the application of the newer techniques does not necessitate a fundamental change in established principles, nor does it require a different standard of safety."3
In that same report, the group described the concept of substantial equivalence in new foods 97 not, as asserted by Millstone et al, as a scientific principle, but merely as a kind of regulatory shorthand for defining those new foods that do not raise safety issues that require special, case by case scrutiny. (The appropriation of the concept and the name, both borrowed from the US Food and Drug Administration's definition of a class of new medical devices that do not differ materially from their predecessors - and, thus, do not raise new regulatory concerns - was suggested by a member of the OECD experts group, senior US White House adviser John J. Cohrssen.) It bears repeating that substantial equivalence was intended to be a conceptual tool for government regulators, not a scientific formulation.
The FDA's approach to novel foods is instructive. The FDA's policy is the most risk-based and scientifically defensible of those currently applied, and, in effect, uses the concept of substantially equivalent. The FDA's 1992 policy on products from "new plant varieties" applies irrespective of whether the plant arose by gene-splicing or "conventional" genetic engineering methods.5 The FDA does not routinely subject foods from new plant varieties to premarket review or to extensive scientific safety tests. Instead, it considers that the usual safety and quality control practices used by plant breeders - mostly chemical and visual analyses and taste testing - are generally adequate for ensuring food safety.
Additional tests are performed, however, when suggested by the product's composition, characteristics or history of use. For example, potatoes are generally tested for a the glycoalkaloid solanine, because this natural toxin has been detected at harmful levels in some new potato varieties that were developed with conventional genetic techniques.
The FDA's policy defines certain safety-related characteristics of new foods that, if present, would require greater scrutiny by the agency.
These include the presence of a substance that is completely new to the food supply, an allergen presented in an unusual or unexpected way (for example, a peanut protein transferred to a potato), changes in the levels of major dietary nutrients, and increased levels of toxins normally found in foods.
(The absence of such characteristics, in effect, defines foods that are substantially equivalent to earlier products, although the FDA does not formally use the concept.)
By considering only recombinant DNA-mediated genetic changes as novel, Millstone et al are inconsistent. They demand extensive, difficult to perform, hugely expensive "biochemical and toxicological" tests on gene-spliced plants, but not on the dozens of new plant varieties improved with more crude traditional techniques of genetic modification such as hybridization that enter the marketplace each year without special labeling or premarket review. They are apparently unperturbed by the fact that many products on the market are from "wide crosses," hybridizations in which genes are moved from one species or one genus to another to create a variety of plant that does not and cannot exist in nature. They seem likewise unimpressed by the fact that thousands of foods containing gene-spliced ingredients or from hybridization have been consumed routinely and safely by consumers in Europe and North America.
All of this suggests that the agenda of Millstone et al is something other than a fair, complete and scientific explication of the issues surrounding the assessment of food safety.
Henry I. Miller, MS, MD [Dr. Miller was the founding director of the US FDA's Office of Biotechnology, 1989-93 and a member of the OECD Group of Experts on Biotechnology.]
Senior Research Fellow, Hoover Institution, Stanford University, Stanford, CA 94305-6010, 650.725.0185, [email protected]
