In the last issue, we looked at hazards associated with eating genetically engineered foods: unexpected allergic reactions; unexpected toxicity; and the development of antibiotic resistance.[1] It is increasingly clear that genetic engineering is neither precise nor predictable; "genetic engineers" are tampering with the instructions for basic cell functions, without understanding fully how those instructions work.

• One source of unpredictable effects is the use of "promoter" genes. As we saw in REHN #716, the aim of genetic engineering is to take a gene from one organism and insert it into another organism. However, organisms have elaborate defense mechanisms to prevent foreign genes from affecting them, so a gene moved from a bacterium to a plant will not automatically work in its new host. To overcome the target organism's defenses and make the new gene function, it is necessary to add a "promoter" gene -- a genetic switch that "turns on" the foreign gene.

  The promoter of choice in most cases is derived from a plant virus called the cauliflower mosaic virus. Known as the CaMV 35S promoter, this genetic sequence causes hyperexpression of other genes. A gene is hyperexpressed when the proteins for which it contains instructions are produced in excessive amounts -- perhaps ten to a thousand times as great as normal levels. Because the CaMV 35S gene is so powerful, in addition to "turning on" the target gene, it may also "turn on" other genes near where it is inserted, causing the engineered cell to display unpredictable new features.[2]

• Plants can defend themselves against the intrusion of foreign genetic instructions through the phenomenon of "gene silencing," in which the cell blocks expression of the foreign DNA. Silencing may occur in unpredictable ways in genetically engineered plants. For example, a recent study found that infection with the cauliflower mosaic virus could trigger silencing of a newly inserted trait for herbicide tolerance, which was linked to the CaMV 35S promoter. Apparently, the plant defended itself against the infection through silencing of the viral genes. At the same time, it silenced other newly-inserted genes.[3]

• Genetically engineered foods may also produce unexplained health effects in laboratory animals. An article published in The Lancet by Stanley Ewen and Arpad Pusztai reports on a study of laboratory rats fed genetically engineered potatoes.[4] The potatoes were designed to produce a substance known as galanthus nivalis agglutinin (GNA), which is ordinarily found in snowdrops (a type of flower). The purpose of adding GNA to potatoes was to increase resistance to certain insects and other pests.

  Ewen and Pusztai worked with three groups of rats. One received the genetically engineered potatoes designed to produce GNA; the second received ordinary, non-engineered potatoes, without GNA; and the third group received ordinary, non-engineered potatoes mixed with a dose of GNA. Ewen and Pusztai studied the changes that occurred in the digestive systems of the rats in each group.

  The researchers found that eating engineered or non-engineered potatoes with GNA was associated with certain changes in the rats' stomachs. In addition, the engineered GNA potatoes were associated with certain intestinal changes NOT found in the rats fed ordinary potatoes laced with GNA. The researchers do not know the reason for these additional changes. They could be due to a "positioning effect" -- the foreign gene may have been inserted at a location in the existing genetic material that caused it to disrupt normal functioning of an existing gene. Or it could be due to the activity of other genetic material inserted along with the target gene, such as the promoter.

  Pusztai was forced to retire from his research position at the Rowett Research Institute in Scotland after he spoke publicly about the results of his work. (See REHN #649.) His article in The Lancet is one of only a few animal feeding studies that have been published on the altered foods that are now present, unlabeled, in our grocery stores.

• In some cases, genetically engineered crops can have altered nutritional content. One study found that glyphosate-tolerant soybeans had significantly altered levels of naturally occurring compounds known as isoflavones, which are thought to have some health benefits.[5] The consequences of changes like this could be minor in some cases and serious in others. The important lesson is that when we eat soy, corn, or other important foods that have been genetically altered, we may not be getting the nutrient mix we could expect in the past. As long as these altered foods are unlabeled, we do not have the information we need to make informed choices about the foods we eat.

  Last fall, corn products in U.S. supermarkets were found to be contaminated with "StarLink" corn, a genetically engineered variety approved only for use as animal feed due to concerns about possible allergic reactions in humans.[6] The contamination was detected by a non-governmental organization, Friends of the Earth, working as part of a national collaborative effort, the Genetically Engineered Food Alert coalition. Had Friends of the Earth not taken responsibility for testing foods -- a function that should be performed by government -- we could have continued to consume unapproved StarLink corn with no way to trace the health consequences. We do not know what other errors may already have occurred; and since we do not know when we are eating genetically engineered foods, we have no way to watch for links between eating these foods and developing certain illnesses. Those who favor the rapid and unregulated introduction of genetically engineered foods into our food supply often say genetic engineering is really nothing new; it is simply an extension of conventional agricultural breeding techniques. In fact, as Michael Hansen of Consumers Union explains in a review article, there are some obvious differences.[2]

• Gene transfers across natural boundaries: Conventional breeding transfers genetic information among organisms that are related to one another -- members of the same species, or related species, or (rarely) of closely-related genera. (Genera is the plural of genus; a genus is a biological grouping that includes multiple species.) Genetic engineering, on the other hand, may transfer genes from any organism to any other organism (fish to fruit, bacteria to vegetables, etc.).

• Location of gene insertion: Variations of a gene are known as alleles. Genes are carried in chromosomes, and each gene has a specific place in a chromosome. Conventional breeding shuffles alleles of existing genes. In general, conventional breeding does not move genes from one place to another in a chromosome. Genetic engineering, on the other hand, inserts genes that were not in the original chromosome of the target organism. These genes may be inserted in unpredictable locations in the chromosome, producing unforseeable changes in the plant.

• Extra genetic material: Genetically engineered foods contain extra genetic material that is unrelated to the target characteristics. This extra genetic material can include vectors, which are added to move genes across natural barriers; promoters, added to "turn on" the foreign genes; marker genes, added to show the engineer whether the target gene has been successfully inserted; and random extra genetic material that the engineer inserts unintentionally. Here is a brief discussion of each of these categories:
  1. Vectors: Genetic engineering often uses "vectors," genetic sequences derived from viruses or bacteria, to move genes into the target cell. One vector used frequently is derived from agrobacterium tumefaciens, a bacterium that causes tumors in plants by inserting DNA from its own genetic code into the genetic code of the plant. A study published in Proceedings of the National Academy of Sciences in January 2001 reported that agrobacterium may be able to insert DNA into human cells as well.[7]

     When agrobacterium infects a plant under natural conditions, the genes are incorporated only into the infected part of the plant; they do not move throughout the plant and are not passed on to subsequent generations. In contrast, when agrobacterium genes are used as vectors in genetic engineering, the resulting plant includes agrobacterium genes in all its cells. Conventional breeding does not require the use of vectors.

  2. Promoters: As we have seen, most genetically engineered crops include the CaMV 35S "promoter" gene to "turn on" the foreign gene and overcome normal cell defense mechanisms. Viral promoters are not necessary for conventional breeding.

  3. Marker genes: As we saw in REHN #716, genetic engineering often involves the insertion of antibiotic resistance marker genes. This does not occur in conventional breeding.

  4. Unintentional additions: Sometimes genetic engineers introduce additional genetic material into the target cell without knowing it. Last spring, for example, newspapers reported that Monsanto's Roundup Ready (glyphosate-tolerant) soybeans contained extra fragments of DNA that the company's genetic engineers were not aware of having introduced.[8]

On the basis of these points, some people would say that genetic engineering is "very different" from conventional breeding, whereas others would say that it is only "somewhat different." Either way, the differences have obvious implications for the ways in which governments should regulate genetically engineered foods. At a minimum, governments should require companies to conduct pre-market safety tests related to the special hazards associated with genetic engineering, and any altered foods allowed onto the market should be labeled.

[To be continued.]

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Rachel Massey is a consultant to Environmental Research Foundation.

1. For a thorough collection of resources on agricultural biotechnology, see AgBioTech InfoNet, maintained by Benbrook Consulting Services at http://www.biotech-info.net/.

2. Michael K. Hansen, "Genetic Engineering is Not an Extension of Conventional Plant Breeding; How Genetic Engineering Differs from Conventional Breeding, Hybridization, Wide Crosses, and Horizontal Gene Transfer," available at http://www.consumersunion.org/food/widecpi200.htm. Also see Michael Hansen and Ellen Hickey, "Genetic Engineering: Imprecise and Unpredictable," in Global Pesticide Campaigner, Vol. 10, No. 1, April 2000, available from Pesticide Action Network (415-981-1771; panna@panna.org; www.panna.org/).

3. Nadia S. Al-Kaff and others, "Plants Rendered Herbicide-Susceptible by Cauliflower Mosaic Virus-Elicited Suppression of a 35S Promoter-Regulated Transgene," Nature Biotechnology Vol. 18 (September 2000), pgs. 995-999.

4. Stanley W. B. Ewen and Arpad Pusztai, "Effect of Diets Containing Genetically Modified Potatoes Expressing galanthus nivalis Lectin on Rat Small Intestine," The Lancet Vol. 354, No. 9187 (October 16, 1999), pgs. 1353-1354.

5. Marc A. Lappe and others, "Alterations in Clinically Important Phytoestrogens in Genetically Modified, Herbicide-Tolerant Soybeans," Journal of Medicinal Food Vol. 1, No. 4 (July 1999), pgs. 241-245.

6. Andrew Pollack, "Case Illustrates Risks of Altered Food." New York Times October 14, 2000. Available at http://www.biotech-info.net/altered_food.html.

7. Talya Kunik and others, "Genetic Transformation of HeLa Cells by agrobacterium," Proceedings of the National Academy of Sciences, published online before print (January 30, 2001). Full text available for U.S. $5 at http://www.pnas.org/cgi/doi/10.1073/pnas.041327598.

8. James Meikle, "Soya Gene Find Fuels Doubts on GM Crops," The Guardian (London) (May 31, 2000). Available at http://www.guardianunlimited.co.uk/gmdebate/Story/0,2763,326569,00.html Also see "Monsanto GM Seeds Contain 'Rogue' DNA," Scotland on Sunday (May 30, 2000). Available at http://www.biotech-info.net/Rogue_DNA.html.

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