RACHEL'S ENVIRONMENT & HEALTH WEEKLY

February 1, 2001

BIOTECH--THE BASICS

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.

** 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.

** 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.

** 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:

a) 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.

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.

b) 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.

c) 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.

d) 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.

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.


January 17, 2001

BIOTECH: THE BASICS BIOTECH: THE BASICS

Genetic engineering is the process by which genes are altered and transferred artificially from one organism to another. Genes, which are made of DNA, contain the instructions according to which cells produce proteins; proteins in turn form the basis for most of a cell's functions. Genetic engineering makes it possible to mix genetic material between organisms that could never breed with each other. It allows people to take genes from one species, such as a flounder, and insert them into another species, such as a tomato -- thus, for example, creating a tomato that has some of the characteristics of a fish.

Starting in the 1980s and accelerating rapidly in the past decade, companies have begun using genetic engineering to insert foreign genes into many crops, including important foods such as corn and soybeans.[1] Just in the past few years, genetically engineered ingredients have begun appearing in many foods in U.S. supermarkets; they have been detected in processed foods such as infant formulas, drink mixes, and taco shells, to name a few examples.[2] These foods are not labeled, so consumers have no way to know when they are eating genetically engineered food.

Genetic engineering is an extremely powerful technology whose mechanisms are not fully understood even by those who do the basic scientific work. In this series, we will review the main problems that have been identified with genetically engineered crops.

Most genetically engineered crops planted worldwide are designed either to survive exposure to certain herbicides or to kill certain insects. Herbicide tolerant crops accounted for 71% of the acreage planted with genetically engineered crops in 1998 and 1999, and crops designed to kill insects (or designed both to kill insects AND to withstand herbicides) accounted for most of the remaining acreage. A small proportion (under 1%) of genetically engineered crops planted in 1998 and 1999 were designed to resist infection by certain viruses.

Genetically engineered herbicide-tolerant crops are able to survive applications of herbicides that would ordinarily kill them. The U.S. food supply currently includes products made from genetically engineered herbicide-tolerant crops including "Roundup Ready" canola, corn, and soybeans which are engineered to withstand applications of Monsanto's Roundup (active ingredient, glyphosate), as well as crops engineered to survive exposure to other herbicides.

Genetically engineered pest-resistant (or pesticidal) crops are toxic to insects that eat them. For example, corn can be engineered to kill the European corn borer, an insect in the order lepidoptera (the category that includes butterflies and moths). This is accomplished by adding genetic material derived from a soil bacterium, BACILLUS THURINGIENSIS (Bt), to the genetic code of the corn. BACILLUS THURINGIENSIS naturally produces a protein toxic to some insects, and organic farmers sometimes spray Bt on their crops as a natural pesticide. In genetically engineered "Bt corn," every cell of the corn plant produces the toxin ordinarily found only in the bacterium.

Unfortunately, genetically engineered crops can have adverse effects on human health and on ecosystems. And by failing to test or regulate genetically engineered crops adequately, the U.S. government has allowed corporations to introduce unfamiliar substances into our food supply without any systematic safety checks.

Here are some of the reasons why we might not want to eat genetically engineered crops:

** Ordinary, familiar foods can become allergenic through the addition of foreign genes.

Genetic engineering can introduce a known or unknown allergen into a food that previously did not contain it. For example, a soybean engineered to contain genes from a brazil nut was found to produce allergic reactions in blood serum of individuals with nut allergies. Allergic reactions to nuts can be serious and even fatal. Researchers were able to identify the danger in this particular case because nut allergies are common and it was possible to conduct proper tests on blood serum from allergic individuals. In other cases, testing for allergenic potential can be much more difficult. When genetic engineering causes a familiar food to start producing a substance previously not present in the human food supply, it is impossible to know who may have an allergic reaction.

** Genetic engineering has the potential to make ordinary, familiar foods become toxic.

In some cases, new characteristics introduced intentionally may create toxicity. The Bt toxin as it appears in the bacteria that produce it naturally is considered relatively safe for humans. In these bacteria, the toxin exists in a "protoxin" form, which becomes dangerous to insects only after it has been shortened, or "activated," in the insect's digestive system. In contrast, some genetically engineered Bt crops produce the toxin in its activated form, which previously only appeared inside the digestive systems of certain insects.[5] Humans have little experience with exposure to this form of the toxin. Furthermore, in the past humans have had no opportunity or reason to ingest any form of the Bt toxin in large quantities. When the Bt toxin is incorporated into our common foods, we are exposed each time we eat those foods.[6, pgs. 64-65.] And of course, a pesticide engineered into every cell of a food source cannot simply be washed off before a meal.

Toxicity can also result from characteristics introduced unintentionally. For example, a plant that ordinarily produces high amounts of a toxin in its leaves and low amounts in its fruit could unexpectedly begin to concentrate the toxin in its fruit after addition of a new gene.

Unpleasant surprises of this sort can result from our ignorance about exactly how a foreign gene has been incorporated into the engineered cell. Foreign genes can be added to cells by various methods; among other options, they can be blasted into cells using a "gene gun," or a virus or bacterium can be used to carry them into the target cells.[7] The "genetic engineer" who sets this process in motion does not actually control where the new genes end up in the genetic code of the target organism. The "engineer" essentially inserts the genes at a random, unknown location in the cell's existing DNA. These newly-inserted genes may sometimes end up in the middle of existing genetic instructions, and may disrupt those instructions.

A foreign gene could, for example, be inserted in the middle of an existing gene that instructs a plant to shut off production of a toxin in its fruit. The foreign gene could disrupt the functioning of this existing gene, causing the plant to produce abnormal levels of the toxin in its fruit. This phenomenon is known as "insertional mutagenesis" -- unpredictable changes resulting from the position in which a new gene is inserted.[8] Genetic engineering can also introduce unexpected new toxicity in food through a well-known phenomenon known as pleiotropy, in which one gene affects multiple characteristics of an organism.

** Genetically engineered crops can indirectly promote the development of antibiotic resistance, making it difficult or impossible to treat common human diseases.

Whatever method is used to introduce foreign genes into a target cell, it only works some of the time, so the "genetic engineer" needs a way to identify those cells that have successfully taken up the foreign genes. One way to identify these cells is to attach a gene for antibiotic resistance to the gene intended for insertion. After attempting to introduce the foreign genes, the "engineer" can treat the mass of cells with an antibiotic. Only those cells that have incorporated the new genes survive, because they are now resistant to antibiotics.

From these surviving cells, a new plant is generated. Each cell of this plant contains the newly introduced genes, including the gene for antibiotic resistance. Once in the food chain, in some cases these genes could be taken up by and incorporated into the genetic material of bacteria living in human or animal digestive systems. A 1999 study published in APPLIED AND ENVIRONMENTAL MICROBIOLOGY found evidence supporting the view that bacteria in the human mouth could potentially take up antibiotic resistance genes released from food.[9] Antibiotic resistance among disease-causing bacteria is already a major threat to public health; due to the excessive use of antibiotics in medical treatment and in agriculture, we are losing the ability to treat life-threatening diseases such as pneumonia, tuberculosis, and salmonella. By putting antibiotic resistance genes into our food, we may be increasing the public health problem even further.

The British Medical Association, the leading association of doctors in Britain, urged an end to the use of antibiotic resistance genes in genetically engineered crops in a 1999 report. "There should be a ban on the use of antibiotic resistance marker genes in GM [genetically modified] food, as the risk to human health from antibiotic resistance developing in micro-organisms is one of the major public health threats that will be faced in the 21st Century. The risk that antibiotic resistance may be passed on to bacteria affecting human beings, through marker genes in the food chain, is one that cannot at present be ruled out," the Association said.

To be continued.

By: Rachel Massey - Who is a consultant to Environmental Research Foundation.

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