Allergies a la Carte: is there a problem with genetically modified foods? (NIEHS News).

What's in a name? Ask genetically modified (GM) foods. They go by many names, ranging from the sinister ("Frankenfoods") to the adoring ("super crops"), depending on who's doing the naming. Although there are clear benefits to the use of this technology--for example, genetic modification could reduce the amount of allergenic substances in foods such as peanuts, the most common food allergen--there is also growing concern among the general public about whether foods modified by recombining DNA from widely different organisms are safe.

A conference titled "Assessment of the Allergenic Potential of Genetically Modified Foods," organized and sponsored by the National Toxicology Program, the U.S. Environmental Protection Agency, the U.S. Food and Drug Administration (FDA), and the NIH, was held 10-12 December 2001 in Chapel Hill, North Carolina, to address this question. Clinicians, bench scientists, government regulators, industry personnel, and policy analysts summarized the current state of the knowledge, examined the issues, and made recommendations for setting research priorities to improve risk assessment.

GM foods are products of plants engineered by biotechnology (no GM animal products are currently approved for the U.S. market). GM crops contain either genes from other plant, animal, or bacterial species, or modified genes constructed in the laboratory and not found in nature. These "borrowed" genes confer some advantage such as pest resistance, herbicide tolerance, longer shelf life in the supermarket, or increased nutritional value.

One unanswered human health question concerns allergenicity. GM foods often contain proteins that humans may not have ingested before or that they may have encountered in a different context (for example, as a glycosylated protein in the original plant but as a nonglycosylated protein in a GM food). Might such novel proteins cause allergic reactions in genetically predisposed people?

Reason for Concern?

In his keynote address, Dean Metcalfe, chief of the Laboratory of Allergic Diseases at the National Institute of Allergy and Infectious Diseases, explained that an allergic reaction is a complex immune system response to an antigen--a protein or piece of a protein that is recognized by the immune system as a potential allergen. Antigens come from foreign proteins found in substances such as food, fungi, bacteria, viruses, pollen, and cells from transplanted tissues. They trigger the production of anti-bodies, which protect the body by neutralizing the "invader."

The immune response generally provides protection against foreign substances. In genetically predisposed individuals, however, exposure to certain proteins may cause an over-reaction to an ordinarily innocuous substance. A later reaction between the antigen and the antibody releases chemicals that affect many different tissues, causing symptoms ranging from minor skin rashes, headaches, vomiting, and diarrhea, to, in rare instances, anaphylaxis and death.

Metcalfe emphasized that the mechanisms involved in allergic reactions are highly complex because of their interdependency on other molecular conditions in both the body and the environment. For example, a person may have an allergic response to a food only when there is also some kind of infection present. People can also develop tolerance or sensitivity to different allergens depending on their exposure and stage of physical development. Babies and children are more prone to allergies because of their immature immune systems. Children are not born with the ability to tolerate food proteins; as they are weaned and begin to eat food, they gradually develop tolerance to food proteins. Approximately 80% of children with allergies outgrow them at some point.

In the United States, around 7 million people have documented food allergies. A Mayo Clinic study published in the August 1999 (part 1) issue of the Journal of Allergy and Clinical Immunology showed that a third of the cases of anaphylaxis in the United States were due to food allergies, whereas a British study published in the December 1996 issue of Clinical and Experimental Allergy showed 50% of the cases in England were caused by food allergies (a discrepancy that may be due to study design). There are 150-175 deaths per year from food allergy reactions in the United States. The majority of people who die from food allergies also have asthma.

The only treatment for food allergies is dietary avoidance, which depends upon being able to identify the source of exposure and treat reactions should they occur. This defines the central problem in regard to the safety of GM foods: because GM foods are not currently labeled, it is impossible to know whether the produce one buys at the supermarket contains possibly allergenic transgenic proteins.

Many scientists believe GM food safety could be well characterized by clinical trials using double-blind food challenge tests in which subjects sample foods under immediate medical supervision. However, such tests are not routinely conducted on GM foods.

Determining Allergenicity

Three criteria are currently used to determine if a transgenic protein is safe for human consumption. First, a sequence comparison to food proteins known to elicit allergic reactions is conducted to see whether the novel protein has a linear sequence of amino acids similar to known allergens. Scientists then test the reaction of antibodies to known food antigens in the new food. Finally, they run test tube assays to determine how well a protein withstands digestion. These same criteria can be useful for crops produced by more conventional agricultural crossbreeding as well. But questions remain as to the effectiveness of these methods for assessing the safety of foods with novel proteins

The bioinformatic tools and data-bases available to compare sequence homology were developed to look at evolutionary relationships between different organisms. In predicting allergenicity, the critical questions involve much more subtle differences within organisms that are not necessarily revealed by available computer programs and search engines. One issue is that there is no standardization of how many amino acids should be looked for in a sequence. The fewer the number of amino acids in the sequence search, the more possible matches, and many of those matches may not be valid indicators of allergenicity. On the other hand, the greater the number of amino acids in the sequence search, the higher the likelihood of missing a sequence that may cause a problem. The question is determining the optimal number of search sequences.

Robert Hamilton, director of the Johns Hopkins Dermatology, Allergy, and Clinical Immunology Reference Laboratory, pointed out that another problem with the comparison of the primary amino acid structure to proteins already in databases is that allergic reactions often arise while or after proteins are metabolized. In such cases, this technique could not reveal allergenic potential.

Research scientist Tong-Jen Fu of the FDA's National Center for Food Safety and Technology discussed the reliability of digestion assays for determining food safety. This concept assumes that all or most food allergens resist digestion more than other foods. This is not necessarily a safe assumption to make; although many food allergens are indeed stable during digestion, many other major allergens are broken down by gastric enzymes, and these cannot be detected in the digestion stability assays. Also, due to a lack of standardization, there is considerable variability in results from different laboratories that use different ratios of enzymes to test proteins in their digestion assays. Furthermore, because in vitro tests use much higher amounts of enzymes than what is found in the human digestive tract, these assays do not simulate what actually occurs in human digestion.

The Future of GM Foods

Although GM foods may offer great benefits, certain concerns must be assuaged before these foods can be accepted as a net gain. Current methods for assessment have not been validated as robust indicators of safety; alternative strategies including animal models and immunoassays need to be developed. The clear identification and articulation of the challenges posed by widespread deployment of novel proteins in our food supply is a vital step toward improving risk assessment and preventing adverse health effects that could arise from eating GM foods.

In an upcoming issue, EHP will publish a mini-monograph resulting from research presented at this meeting.