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North Central Regional
Extension Publication NCR #551 |
Note to the reader: Most genetically engineered fruits and vegetables have not received final approval for marketing from the Food and Drug Administration (FDA) at this time. This publication is designed to explain the science of genetically engineered fruits and vegetables, not to give the perception of pre-approval endorsement by the United States Department of Agriculture (USDA) or by the publishing state.
Genetic (recombinant DNA) engineering is the manipulation of DNA molecules to produce modified plants, animals, or other organisms. DNA (deoxyribonucleic acid) is a double-stranded molecule that is present in every cell of an organism and contains the hereditary information that passes from parents to offspring. This hereditary information is contained in individual units or sections of DNA called genes. The genes that are passed from parent to offspring determine the traits that the offspring will have.
Through the work of the last 20 years, scientists can now isolate the gene or genes for the traits they want in one animal or plant and move them into another. It is not really that simple, since some traits involve more than one gene and some genes are hard to find. Nevertheless, each year scientists are learning better ways to locate and transfer genes.

Other researchers are using genes from chicken embryos and insect immune systems to try to make potatoes more disease resistant.
Another company is working to improve the flavor and sweetness in melons produced for the winter markets. Its researchers believe the same technology can be applied to peaches produced during the main crop season (Eckles).
To withstand the rigors of shipping, tomatoes must be picked at a stage the growers call "mature-green." Mature-green tomatoes have already absorbed all the vitamins and nutrients from the plant that they can, but have not started to produce the natural ethylene gas that triggers ripening.
The next step, called "degreening" or "ripening initiation," involves putting the green tomatoes in ripening rooms where ethylene gas is released. The green tomatoes spend 3 to 4 days in the ripening room before they are shipped at temperatures not lower than 50 degrees. Cooler temperatures destroy tomato flavor.
When consumers see tomatoes at the grocery store, they probably still are 3 to 4 days away from being ripe. Unfortunately, many consumers think that shipped-in winter tomatoes lack the taste and texture of vine-ripened tomatoes. In fact, according to one study, tomatoes rank #1 in produce items with which consumers are least consistently satisfied (The Packer's Study).
Calgene's scientists isolated the PG gene in tomato plants. The next step was to convert the tomato PG gene into a reverse image of itself called an antisense orientation. The scientists called this "reversed" tomato gene the Flavr Savr gene and reintroduced it into the plants.
In order to tell if the Flavr Savr gene was successfully reintroduced into the plants, Calgene scientists attached a gene that makes a naturally occurring protein that renders plants resistant to the antibiotic kanamycin. By exposing the plants to the antibiotic, Calgene scientists could tell which plants had accepted the Flavr Savr gene. The ones unaffected by kanamycin grow to have the desired traits of the Flavr Savr.
Once in a tomato plant, the Flavr Savr gene attaches itself to the PG gene. With the Flavr Savr gene adhering to it, the PG gene cannot give the necessary signals to produce the polygalacturonase enzyme that destroys pectin. One way of visualizing this is to imagine how hard it would be for people to function if we each had a mirror image of ourselves stuck to us.
If approved by the FDA, those plants with the Flavr Savr TM gene will be grown for commercial tomato production. The seeds will be planted and grown like any other fresh tomato plants, except the tomatoes can spend more days on the vine until they reach the desired flavor and texture before shipping. (Figure 1 summarizes the process.)
1. Market Demand
Before introducing any new product, including genetically engineered fresh produce, a company must be sure that the product has a market. Domestic consumption of fresh tomatoes is estimated at about 5 billion pounds a year with an estimated retail value of approximately $33.5 billion (Calgene, factsheet). Calgene Fresh, Inc., estimates that 85 percent of U.S. households purchase fresh tomatoes each year, with more than 50 million consumers purchasing three pounds of fresh tomatoes in a typical month. This level of consumption is occurring despite consumer dissatisfaction with the quality of fresh tomatoes.
2. Patenting the Technology
Patents protect a company's legal rights to a technology it invented. In February 1989, Calgene, Inc., was issued a U.S. patent on the use of the tomato polygalacturonase (PG) gene sequence, including the antisense (reverse) orientation of the gene. In April 1992, the company was issued a broad patent covering the use of the antisense technology in all plants to partially or completely inhibit specific gene expression.
After a patent is issued, other companies may challenge the patent if they believe they developed the technology first. At least two companies are challenging Calgene's patenting of the technology used to develop the Flavr Savr tomato.
3. Pre-market Testing
The FDA and the USDA require a company to conduct rigorous pre-market testing of genetically engineered food products before they become commercially available. The Flavr Savr tomato is probably the most studied tomato in history. It has undergone more than four years of comprehensive pre-market tests that examined the nutritional value, potential toxins, processing and horticultural traits, fungal resistance, softening rate, and other characteristics. In addition, Calgene Fresh, Inc., voluntarily submitted its safety data for rigorous review by an external panel of nationally recognized food safety experts. Their studies demonstrate that the Flavr Savr tomato is as safe and nutritious as any other fresh tomatoes.
Test results were submitted to both the FDA and the USDA, opened for public comment by both agencies, and published in a technical report that is available to the public (Redenbaugh et al.).
4. Regulatory Status
The FDA regulates food and food additives, including new genetically engineered foods. The USDA regulates whether genetically engineered plants can be grown and under what conditions.
In November 1990, Calgene requested an Advisory Opinion from the FDA on the use of the kanamycin resistance marker gene in tomatoes. In October 1991, it requested the FDA to issue a separate Advisory Opinion on the status of the Flavr Savr tomato as a food (under regulatory definition). To assure a thorough review of the safety of the new product, the company subsequently asked the FDA to review the marker gene used in the Flavr Savr as a food additive.
In May 1992, the company filed a Petition for Determination with the USDA requesting that the agency determine that the Flavr Savr tomato is a non-regulated article under federal law. In October 1992, the USDA determined the Flavr Savr tomato does not present a plant pest risk and therefore need not be regulated.
5. First on the Market
In April of 1994, outside experts of the FDA's Food Advisory Committee discussed the agency's evaluation of the Flavr Savr tomato in a public meeting. Members of the committee agreed with the FDA's preliminary assessment that all relevant safety questions about the new tomato had beer) resolved.
On May 18,1994, the FDA announced its findings that the Flavr Savr tomato is as safe as tomatoes bred by conventional means, in effect giving Calgene Fresh approval to market its new product. Calgene Fresh immediately began offering limited quantities of the new tomatoes grown from Flavr Savr seeds under the MacGregor'sR brand in selected midwestern and California markets.
Current methods of controlling the viruses focus on controlling aphids through repeated spraying of insecticides or oils. These preventive measures have failed to effectively control aphids that spread the viruses.
This approach bypasses aphid control methods to focus on the viruses themselves. The number of aphids in a squash field is less important if the squash cannot be infected by the disease they transmit.
The genes that produce the coat protein of the two viruses WMV-2 and ZYMV were introduced into the bacteria. Two DNA molecules called plasmids that were located within the bacteria transferred the two virus genes into squash plant cells.
Once inside the squash plant cells, scientists hoped the virus genes would become part of the squash plant's DNA, "vaccinating" it against the viruses. To be sure, Asgrow scientists attached marker genes for the antibiotic neomycin phosphotransferase to the virus genes before they were introduced into the bacteria. Plant cells containing the marker gene with the attached virus genes could grow more rapidly in the presence of the antibiotic than those that did not.
Scientists selected the plant cells that they knew had the virus genes and grew them into plants. With subsequent selections, researchers were able to separate the marker genes from the resistance genes, so the ZW-20 line contains no marker genes for antibiotic resistance.
1. Market Demand
Commercially acceptable squash varieties currently do not exist that can resist even one of the four most common viruses that affect squash. Asgrow believes that genetic engineering offers a means of developing squash hybrids that are protected from virus infection without altering the plants' desirable commercial or horticultural characteristics.
2. Patenting the Technology
Asgrow has applied for patents to protect the technology and the plants made resistant to the viruses by this approach. No decision has been made by the Patent Office regarding these applications, as this is written.
3. Pre-market Testing
Pre-market tests of the ZW20 squash compared its disease and pest resistance, pollination characteristics, weediness, possibility of genetic transfer to related species, mixing of the viral coat proteins with other virus proteins, and safety for human consumption to that of traditional squash plants. According to Asgrow, nutritional comparisons were not done because all squash is low in food value and does not contribute significantly to consumers' nutrient intake. Except for its resistance to the targeted viruses, the data indicated that the ZW-20 squash has the same horticultural characteristics as traditional varieties.
Asgrow says that the new squash carries no more risk of developing undesirable characteristics, and sometimes less, than traditional squash plants. For example, the company examined squash from supermarket shelves and found higher protein levels of WMV-2 and ZYMV viruses within fruit from plants that had been naturally infected with viruses in the fields than in the ZW-20 squash.
Pre-market testing results submitted to the USDA's Animal and Plant Health Inspection Service are available to the public from that agency.
4. Regulatory Status
In July 1992, Asgrow asked the USDA to deregulate the ZW_20 modified squash plant because the company does not believe that the plant presents a plant pest risk or is otherwise harmful to the environment. After reviewing the data provided by Asgrow and opening the data for public comment, the USDA requested additional data, which Asgrow has provided, and asked for more public input. In May of 1994, the USDA determined in a preliminary finding that the ZW-20 squash would not have a negative impact on the environment and opened a third period for public comment. According to a company spokesman, Asgrow is planning commercial introduction of the squash, after regulatory approval (Ag Biotechnology News).
In May 1992, the FDA determined that foods derived from new plant varieties essentially will be regulated no differently than foods created by conventional means, unless special circumstances apply (Federal Register). The FDA released guidelines to help companies decide whether they need FDA approval of a genetically engineered food product. The FDA determined that a special review of a genetically engineered food product would be needed only when specific safety issues were raised, such as if the gene for peanut protein, to which some people are allergic, was inserted into a different food like a tomato. Specifically, companies were told that an evaluation to assure food safety may be required if one or more of the following subheadings apply to their product (Federal Register):
2. Known Toxicants (has significantly higher levels of toxicants than present in other edible varieties of the same species)
3. Nutrients (significantly alters levels of important nutrients)
4. New Substances (differs significantly in composition from such substances currently found in food)
5. Allergenicity (contains proteins that cause an allergic response)
6. Antibiotic Resistance Selectable Markers (contains marker genes that could produce antibiotic resistance in people who consumed the food)
7. Plants Developed to Make Specialty Nonfood Substances (plants developed to make substances like pharmaceuticals or polymers that will also be used for food)
8. Issues Specific to Animal Feeds (plants that will be used for animal feeds)
The FDA policy notice of May 1992 may be revised in the future as the agency responds to new scientific developments and the comments of the public and the scientific community.
For example, in June of 1992, shortly after the FDA's policy notice was released, a group of New York City chefs called for an international boycott of genetically engineered foods. About the same time, a coalition of farmers, consumers, and environmentalists known as The Pure Food Campaign petitioned the FDA for government-required testing and labeling of all genetically engineered foods.
In contrast, a USDA-supported survey of 1,200 consumers nationwide found that nearly two-thirds (64 percent) supported using biotechnology to produce food (Food Insight). In the same survey, 71 percent agreed that biotechnology could benefit people like themselves, and 66 percent expressed interest in learning more about biotechnology.
Several food industry groups, including the Grocery Manufacturers of America (GMA) and the Produce Marketing Association (PMA) have issued position papers expressing confidence in the safety of foods developed through biotechnology (GMA, PMA). The GMA paper cites findings by the American Medical Association's Council on Scientific Affairs, a Joint FAO/ WHO Consultation released by the World Health Organization, the National Research Council, and the FDA that foods developed through biotechnology are similar to other foods developed by traditional methods and are not inherently less safe.
The American Dietetic Association has written a position paper concerning biotechnology and the future of food. It is their position that the techniques of biotechnology are useful for the improvement of food quality, nutritional value, and variety and for making the production, processing, distribution, and waste management of food more efficient (Journal of American Dietetic Assoc.). The position paper advises dietetics professionals to understand the vocabulary and implications of biotechnology and to accept the role of consumer advocates in questions of labeling and regulation of foods developed through biotechnology techniques.
Not everyone views genetically engineered foods, including fruits and vegetables, as a welcome development. Consumer groups, some with international organizations, have expressed concerns in several areas. Some proponents of using biotechnology to produce food point out that opponents' objections are not always as valid as they seem.
Others point out that several companies have genetic engineering projects under way to increase, not lower, the health attributes of foods.
Proponents assert that genetic engineering is more precise than traditional crossbreeding methods and carries less risk of undesired traits being transferred. In traditional methods, thousands of genes are passed on with each generation, besides the gene of interest. Genetic engineers can narrow the transfer to the genes they select.
The FDA does not view the problem of unexpected genetic effects as unique to genetic engineering. In its May 1992 policy statement, the agency points out that "virtually all breeding techniques have potential to create unexpected effects" (Federal Register).
About 25 years ago, a plant breeder in Canada, experimenting with a new potato variety developed by the USDA for its disease resistance, reportedly became ill after eating some. Evidently, levels of a naturally occurring toxin in the potato were elevated during the traditional breeding process.
The FDA notes that today's traditional plant breeders use well established practices to eliminate plants with adverse traits prior to commercial use. Presumably, plant breeders that help bring transgenic plants to market can do the same
The FDA, in its May 1992 policy notice, recognized the importance of evaluating concerns about the commercial use of antibiotic resistance marker genes in food, especially those to be used widely. The FDA noted that the agency is currently evaluating these issues as they apply to the kanamycin resistance marker gene. In addition, some scientists are working to develop ways to remove marker genes from a plant after the gene transfer is made.
Biotechnology supporters argue that the FDA already has advised companies to thoroughly test and label genetically engineered foods that contain known allergens. Some say that because there currently is no practical way to predict which new proteins will produce an allergic response, testing and labeling is all that can be reasonably expected at this point.
On the other hand, it can be argued that this situation is not unique to genetically engineered foods. Practicality prevents testing any new product on every specialized population before it is marketed.
Genetic changes that can lead to unexpected toxins can occur not only in genetically transformed plants, but also in plants developed through traditional breeding practices or as a natural part of growth. Proponents agree with the FDA view that the likelihood that food plants with a long history of use will develop unexpected toxins is "extremely low."
Others cite the fact that the potential of pests to develop resistance against the defense mechanisms of crops is well-known and is not unique to genetically engineered plants. Insects may develop resistance to a crop defense no matter how it was developed. The crop defense might be a chemical or biological agent, a gene already in the crop species and transferred to commercial plants by conventional plant breeding methods, or a gene introduced by recombinant DNA technology. Companies are working on strategies to avoid possible resistance problems.
Proponents maintain that every company or individual that produces food by using recombinant DNA technology is legally responsible for assuring its safety and quality before it enters the food supply.
Some companies resent the implication that test results from their own laboratories are false. After all, they argue, it's to their benefit to produce a safe, beneficial food product for consumers. There's no profit in bad products. Besides, many companies engage independent laboratories to test their products. Calgene Fresh, Inc., for example, submitted its safety data on the Flavr SavrTM TM tomato to an external panel of nationally recognized food safety experts for rigorous review. The reality is that today's FDA does not have the people or the money to conduct its own tests on every new food product.
Supporters of biotechnology foresee a different day when not one, but many improved crop varieties could flourish in areas of the world that currently cannot produce enough food crops for their populations.
Others point to the need for labeling for individuals whose religions or lifestyles have dietary restrictions. For example, eating fruit that has been transformed with an animal gene may be objectionable to vegetarians or to members of a religion that forbids eating meat from that animal.
Most supporters of genetically engineered foods recognize the need for labeling if the composition of a food has changed substantially or allergens or toxins are a possibility. However, some worry that labels placed on all genetically engineered foods would be interpreted as warning labels.
Calgene Fresh says it intends to voluntarily identify its Flavr Savr tomato and will provide consumers with "point-of-purchase materials that explain the role of biotechnology in delivering a better tasting tomato" (Calgene, Questions and Answers).
In fact, one seed company plans to release improved tomatoes and melons in the mid to late 1990s with enhanced vitamin-content tomatoes available about 2000 (Eckles). It is also developing projects to improve the texture and taste of other high value soft fruits, such as peaches and strawberries. These products will probably hit the market in the late 1990s to 2000.
The bottom line for genetically engineered foods will be the products' own merit, consumer trust, and economics. Will consumers be afraid to eat a genetically engineered tomato, even if it does look red and juicy in January? If they are willing to eat it, will they be willing to pay for it?
No doubt, the years of research, development, and testing required to develop a new genetically engineered food will demand a higher price at the grocery store. Calgene Fresh has already declared that the "value delivered in the Flavr Savr tomato will command a premium price" (Calgene, Questions and Answers).
Whether the premium price of genetically engineered vegetables, in trust as well as dollars, is too high is something consumers will decide.
References
Ag Biotechnology News. "More Data Needed on Asgrow Squash." November 1992. p. 16.
Calgene Fresh, Inc. "Fact Sheet: Flavr Savr Tomatoes." 1033 University Place, Suite 450 , Evanston, Illinois 60201, p 1.
Calgene Fresh, Inc. "Flavr Savr Tomato: Questions & Answers." 1033 University Place, Suite 450, Evanston, Illinois 60201, p 2-3.
Canine, Craig. "A Matter of Taste ... Who Killed the Flavor in America's Supermarket Tomatoes?" Eating Well. January/ February 1991, p. 41-55.
Dyson, John. "The Amazing GreenGene Revolution." The Reader's Digest. October, 1992, p. 53-57.
Eckles, Jim. Personal and written communication. Zeneca Ag Products, a subsidiary of Imperial Chemical Industries. Wilmington, Delaware, 29 March 1993.
Federal Register. "Statement of Policy: Foods Derived from New Plant Varieties; Notice." Part IX, Department of Health and Human Services, Food and Drug Administration, Vol. 57, No. 104, Friday, May 29, 1992, p. 22984-23005.
Food Insight. "Consumers Support Use of Food Biotech." September/ October 1992. p. 6.
Grocery Manufacturers of America, Inc. "Safe Foods Developed Through Biotechnology: Nutritious, healthful, abundant and good tasting." 1010 Wisconsin Avenue, N.W., Washington, D.C. 20007. October 1992.
Journal of the American Dietetic Association. "Position of The American Dietetic Association: Biotechnology and the Future of Food." Vol. 93, No. 2, February 1993. p. 189-192.
Krimsky, Sheldon. "Tomatoes May Be Dangerous to Your Health." The New York Times. 1 June 1992, Op-Ed page.
Monsanto. "Tomatoes With Lasting Flavor." The Agricultural Group, 700 Chesterfield Parkway North, St. Louis, Missouri 63198.
Produce Marketing Association. "Produce Marketing Association Position Paper on Biotechnology." 1500 Casho Mill Road, P.O. Box 6036, Newark, Delaware 19714-6036. October 1992.
Redenbaugh, Keith; Hiatt, W.; Martineau, B.; Kramer, M.; Sheehy, R.; Sanders, R.; Houck, C.; and Emlay, D. Safety Assessment of Genetically Engineered Fruits and Vegetables: A Case Study of the Flavr SavrTM Tomato. Boca Raton, Florida: CRC Press, Inc., 1992. ISBN 0-8493-4803-X.
Sagan, Kathyrne V. "The Great Tomato Debate ... Is Bioengineered Food Safe?" Family Circle, October 13, 1992, p. 151-160.
Sugarman, Carole. "Splice and Dice -Genetic Engineers on the Cutting Edge." The Washington Post. 3 June 1992, p. El, E4.
The Packer's 1993 Fresh Trends Consumer Profile Study, p 82.
| Written by Glenda D. Webber, Office of Biotechnology, Iowa State University, Ames, Iowa. | Credits
Page 1 Photo courtesy of Monsanto.
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