Recombinant DNA Biotechnology in Balance: Benefits and Concerns of a New Technology

New technologies rarely receive a broad and enthusiastic welcome. Canned food, for its first hundred years, was viewed apprehensively, and not without reason. In those pre-bacteriology days, it was far more an uncertain art than a solid science. Pasteurized milk, a life-saving technology in its elimination of the microorganisms that cause tuberculosis and undulant fever, was originally viewed with deep suspicion. Artificial insemination of farm animals—critical in selective breeding of improved livestock—was regarded as tampering with nature. Recombinant DNA biotechnology is no exception.

Although rDNA biotechnology offers numerous benefits, it also has raised several issues of consumer concern. A thorough analysis of these concerns reveals that many stem from not fully understanding the science involved and how these potential risks have already been addressed. This report explores the benefits and evaluates the concerns in order to contribute to civil and rational dialogue which alone can deal effectively with both scientific issues and consumer concerns about this new technology.

Specific Benefits

Stronger Plants. Recombinant DNA biotechnology is the latest in a long line of tools that plant breeders have used to enhance plant availability, survival, and growth to benefit people. In little more than a century, starting with hybridization, which was commercialized in the first decade of the 20th century, scientific breakthroughs enabled new types of plants, such as seedless watermelons and grapes, to be produced. Plant breeding often has been successful in producing plants with increased pest and disease resistance, while retaining high yields, taste, and processing attributes. Apple and pear production is constrained by the bacterial disease called fireblight, first described in the 1870s. No satisfactory antibacterial compounds or adequate resistance to the disease is available in apples desired by consumers. Recombinant DNA biotechnology research has produced the first trees to resist this devastating disease.

The susceptibility of a plant to biotic and environmental stresses, such as temperature extremes, exposure to heavy metals such as aluminum, and salt and drought tolerance is heavily affected by the plant’s genetic composition and structure. For example, some leaves have evolved to conserve moisture and resist heat or freezing. Breeders have changed leaf and stem architecture to capture more sunlight and allow for greater air flow through the leaf canopy.

Improved Nutrition. Specific foods can be developed to correct malnutrition problems that are unique to different regions of the world. To this end, plants can be modified to provide increased and more stable quantities of essential amino acids, vitamins, or desirable fatty acids. For example, “golden rice” has been genetically modified through rDNA biotechnology to have increased betacarotene content, which may help to overcome the severe vitamin A deficiencies which cause millions of poor children to go blind or die every year in low-income, riceconsuming cultures. A related product of rDNA biotechnology may also help eliminate the iron deficiency that threatens hundreds of millions of women and babies with birth complications each year.

Probiotics are living microorganisms, typically delivered through foods, that offer benefits to health and well being that are beyond basic nutrition. Selected members within the Lactobacillus and Bifidobacterium genera are considered key probiotic species because they survive passage through the gastrointestinal tract and exert benefits there; such as stimulation of the immune system and balancing a healthy microbial flora. Recombinant DNA biotechnology is expected to play an important role in identifying the probiotic strains capable of eliciting certain health benefits.

Higher Crop Yields. Plants also can be modified to grow well in areas of low production potential. For example, toxic metals, such as aluminum and manganese, are widely present in “acidic” tropical soils, which account for nearly half the arable land in the tropics. These metals reduce root growth, cutting yields by up to 80 percent. To produce acid-tolerant crops, two researchers in Mexico inserted a gene from a bacterium into tobacco and papaya. The plants thus secrete citric acid from their roots, chelating these toxic metals. The yield gains now anticipated from making such soils accessible will be critical to protecting the tropical forests, which contain most of the world’s species of plants and animals.

Reduced Allergenicity. Recombinant DNA biotechnology also offers the opportunity to decrease or eliminate the allergenic proteins that occur naturally in specific foods. For example, rDNA biotechnology has already been used to dramatically reduce the levels of the major rice allergen. Similar approaches could be attempted with more commonly allergenic foods such as peanuts.

Medical Benefits. Recombinant DNA biotechnology brings closer to reality the prospect of commercial production in plants of edible vaccines and therapeutics for preventing and treating animal and human diseases. Possibilities include a wide variety of compounds, ranging from vaccine antigens for hepatitis B and Norwalk viruses, bacteria (Pseudomonas aeruginosa and Staphylococcus aureus), to vaccines against cancer and diabetes. In addition, genetically- modified strains of probiotic microorganisms are also possible vehicles for successful delivery of vaccines and digestive aids, such as lactase, through the stomach and the small intestine. Recombinant DNA biotechnology-derived vaccines are potentially cheap, convenient to distribute, and simple and safe to administer. In 1998, scientists reported the first successful human clinical trials with an edible vaccine against a pathogenic strain of Escherichia coli.

Researchers also have developed a system to produce in tobacco plants a therapeutic vaccine against non- Hodgkin’s B-cell lymphoma in mice. Eighty percent of mice receiving the plant-derived vaccine survived the lymphoma, while all untreated mice died within three weeks after contracting the disease. A similar approach was used to develop a vaccine against insulin-dependent diabetes mellitus (IDDM). Insulin and pancreatic glutamic acid decarboxylase (GAD), linked to the on set of IDDM, are candidates for use as oral vaccines. Scientists have developed a potato-based insulin vaccine that is almost 100 times more powerful than the existing vaccine in preventing IDDM. Diabetes-prone mice fed potatoes engineered to produce GAD had reduced incidence of disease and immune response severity.

Healthier Farm Animals. Advances in genetics and rDNA biotechnology make it possible to envision ways of improving the nutritional content of animal feed by directing the plant to produce a more nutritious product. Plant breeders used rDNA biotechnology to develop a corn that is easier for farm animals to digest. A further improvement came with the development of nutritionally dense corn, which has increased amounts of oil, protein, and essential amino acids necessary for optimal animal growth. In all crops it seems reasonable to expect additional improvement through further enhancements in oils and fatty acids, protein, starch, and carbohydrates, and enhancements in vitamins, antioxidants, and mineral composition. Recombinant DNA biotechnology has also helped develop an animal feed corn with lower levels of phytate. This improvement reduces phosphorous and nitrogen in animal waste. People who live near large farms especially benefit from this improvement, because it reduces the intense odors that may waft their way.

The techniques being used to develop edible human vaccines are also being applied to develop vaccines for animals. Researchers have already demonstrated production in plants of a vaccine against transmissible gastroenteritis virus, which protected swine in clinical trails against the virulent pathogen.

Environmental Benefits. Farmers and producers have enthusiastically embraced the new varieties of rDNA biotechnology- derived crops that exhibit increased resistance to insects. Examples include corn and cotton with Bacillus thuringiensis (Bt) genes for insecticidal proteins, tolerance to herbicides (corn, cotton, soybeans), and virus-resistant crops including squash, cucumbers, and papaya. In 1998, 45 percent of farmers had higher yields of Bt corn compared to conventional corn, and nearly 26 percent of farmers growing Bt corn reported a decrease in pesticide use.

Recombinant DNA biotechnology also makes it possible to use herbicides that are less harmful to the environment. The herbicide glyphosate, for example, rapidly degrades in soil, breaking down into harmless carbon dioxide and water, unlike earlier herbicides that persisted in the environment and contaminated groundwater. Glyphosate is replacing these herbicides with the introduction of rDNA biotechnology-derived, glyphosate-tolerant plant crops such as canola and soybeans. As an added benefit, these canola plants require only one herbicide application, instead of two.

New Ingredients. Recombinant rDNA biotechnology can lead to improvements in microorganisms such as bacteria, yeasts, and molds that help convert milk, cereals, vegetables, and meats into a plethora of fermented products, including cheese, cultured milk, sourdough bread, pickles, and sausages. It also can lead to improvements in production of basic ingredients and nutrients such as organic acids, amino acids, vitamins and enzymes.

Enzymes have historically played a key role in production of bread, cheese, and alcoholic beverage production. Today, enzymes remain indispensable to modern food processing, and many are produced using rDNA biotechnology. Chymosin, used to clot milk in cheesemaking, was the first enzyme produced by rDNA biotechnology for use in food. Traditionally, chymosin was obtained from rennet extracted from the fourth stomach of young calves. Rennet supplies faced major declines as calf slaughter decreased during a period of increasing worldwide cheese production. Chymosin produced through rDNA biotechnology is substantially more pure than traditional rennet. The Food and Drug Administration (FDA) concluded in 1990 that rDNA biotechnology-derived chymosin is identical to its natural counterpart and, therefore, is acceptable for use in foods. Use of rDNA biotechnology-derived chymosin now exceeds 80 percent of the global market.

Food Safety Improvements. Preliminary studies have shown that rDNA biotechnology-derived foods and food ingredients may have food safety benefits. For example, preliminary studies by the U.S. Department of Agriculture’s (USDA) Agricultural Research Service have shown that Bt corn had lower levels of fumonisin, a potential cancer- causing agent often found at elevated levels in insect-damaged kernels. In Bt corn, fumonisin levels were 30-to-40 fold lower than in non-Bt corn varieties. Mycotoxins like fumonisin are both a public health issue and an export issue, as European and Asian markets have refused to import U.S. corn due to unacceptable levels of mycotoxins. It may be possible to create corn varieties with greater resistance to a variety of insects, leading to lower levels of mycotoxin contamination.

Economic Benefits. The most widespread rDNA biotechnology- derived crops in the United States are soybean, cotton and corn. In 1999, 35 percent of U.S. corn acreage (77.4 million acres) was made up of either insect-tolerant (23 percent) or herbicide-tolerant cultivars; 45 percent of the cotton acreage (14.8 million acres) was insect tolerant; and 54 percent of the soybean acreage (72.9 million acres) was herbicide tolerant. A 1997 USDA study found that herbicide-tolerant soybeans reduced farm input costs by 3 to 6 percent and increased average yields by more than 13 to 18 percent in most regions of the United States.

Evaluation of Concerns

Public Sector Access. The increasing role of the private sector in research and the aggressive patenting of genes and tools may limit access to the necessary materials and processes for pioneering research in the public sector. If concentrated private sector control of critical genes and technologies becomes a problem, appropriate policy responses include reducing the scope of patents on genes and platform technologies, including obligatory licensing requirements in patent awards, and increasing public sector funding of basic research in order to increase the amount of plant genetic information and rDNA biotechnology information in the public domain. Public-private partnerships are also critical to bring the benefits of rDNA technology to all the world’s people. Another policy option is to provide a set of incentives to increase private sector research on crops and traits perceived to have high public benefits.

In two recent promising developments, one firm decided to make its extensive rice genome data available to the public for research purposes, and the company that developed the “golden rice” announced it will grant patent licenses without charge for the introduction of its product.

Agribusiness Consolidation and Competition. Certain segments of the commercial seed markets have become highly concentrated. At least four or five large agricultural and life science companies are aggressively competing for market share in the corn, soybean, oilseed, and vegetable seed markets. One company has expanded its soybean sales in the North American market and has realized strong sales growth for vegetable and horticultural seeds. Another company is actively marketing herbicide-tolerant corn and canola seed and has recently established itself as a strong competitor in the vegetable seed market with the acquisition of two smaller companies. Potential abuses of market power by dominant firms is adequately addressed in the public sector by maintaining a vigilant anti-trust policy. If competing firms can easily enter profitable markets, dominant firms will be prevented from charging exorbitant prices.

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Pest and Disease Resistance. Corn and potato have both been successfully transformed with genes from various strains of the soil bacterium B. thuringiensis. These genes encode toxic proteins with specific effects on certain groups of insects. The pollen of Bt plants was reported to be toxic to the larvae of monarch butterflies feeding on the leaves of milkweed plants. However, field studies at multiple locations—Maryland, Iowa, Nebraska, and Ontario— found that a lethal dose of Bt pollen spreads only a few feet from its source, not the hundreds of feet reported earlier. The Environmental Protection Agency’s (EPA’s) recent suggestion that farmers locate the required 20 percent corn refuge areas around the perimeter of the fields, coupled with the limited movement of corn pollen, would virtually eliminate any remaining risk of Bt pollen to monarch butterfly larvae.

Resistance to all methods of pest control has been and continues to be a major problem in agriculture. For the first time in the case of rDNA biotechnology-derived products, government, industry, and farmers are trying to manage the use of Bt corn to extend its useful life. Since the widespread use of rDNA biotechnology-derived Bt is likely to shorten its useful life and that of Bt used as an insecticidal spray, refuges that contain non-rDNA biotechnology- derived crop plants to reduce the selection pressure on target insects are being employed to delay the accumulation of resistant forms. It is too soon to know how effective this strategy will be.

Transgene Spread by Pollen. There is a concern that genes for herbicide tolerance may spread via pollen from rDNA biotechnology-derived crops to other native plants. It is theorized that the genes might become established in weed populations, creating forms that would become difficult to control in the future. For soybean, corn, and most other crops in the United States, this outcome is unlikely due to the absence of related wild species that are either already weeds or have the potential to become weeds.

For those crops that are themselves of weed origin, this possibility is a more serious issue. In some rice growing regions, red rice is a weed in rice paddies. Because it readily hybridizes with cultivated rice, it would be very unwise to use herbicide-tolerant rice in such regions since the red rice population would rapidly acquire herbicide tolerance, denying rice farmers a tool for controlling it. It is also generally regarded as unwise to produce herbicidetolerant sorghum for use in the United States due to the likelihood of outcrossing to Johnson grass, a particularly difficult weed to control in agriculture.

Contamination of Organic Crops. The organic farming community has decided at this time not to use rDNA biotechnology-derived crops. Thus, if an organic crop, grown for its harvested seed, is planted near a transgenic crop of the same species, it is likely that some seeds will result from fertilization by pollen carrying a transgene. Sensitive DNA detection techniques available could detect the transgene signature and invalidate the crop’s organic certification. Reasonable isolation distances between crops should prevent this problem.

Virus Resistance. Recombination between a virally derived transgene and another virus has been suggested as a possible source of a new virus with enhanced virulence. Such recombination has been shown in laboratory studies, especially with high selection pressure. Just this year, however, a National Research Council committee concluded that “most virus-derived resistance genes are unlikely to present unusual or unmanageable problems that differ from those associated with traditional plant breeding for resistance.”

Monoculture and rDNA Biotechnology. The rapid and widespread adoption in the United States of herbicidetolerant soybean and insect-resistant corn could leave many farmers susceptible to epidemic pests and diseases. Even though the risk is probably not high, it would be prudent to diversify the germplasm by making sure there is adequate backup capability that can provide alternative varieties in the event of catastrophic failure. The best way of doing this is still to safeguard germplasm collections and to encourage a broad spectrum of plant breeding activities and diversity in rDNA biotechnology-derived crops.

Environmental Monitoring. Some have raised concerns that there is inadequate monitoring of rDNA biotechnology- derived crops and foods. The road map for transgenic seeds from initial generation through testing and regulatory approval is similar to that for traditional seed, with additional steps to meet regulatory requirements. With a higher degree of regulatory oversight for all foods produced by rDNA biotechnology, there is less likelihood of adverse reactions reaching consumers than with conventional foods.

Extensive field testing involving multiple sites and multiple years typically occurs before seed amplification and release of a commercial seed product. Most states test and release public varieties in a tracked process that produces certified seed. Most states also provide public testing in a fee-based evaluation at a few sites. Private sector seeds are sometimes submitted for public testing, but usually undergo similar field evaluations and may be tested in hundreds of sites.

Allergenicity. Most food allergies are traced to proteins in eight sources: milk, eggs, fish, crustaceans, peanuts, tree nuts, soybeans, and wheat. While virtually all food allergens are proteins, only a small fraction of the proteins found in nature (and in foods) are allergenic. Since genetic modifications involve the introduction of new genes into the recipient plant and since these genes would produce new proteins in the improved variety, the potential allergenicity of foods developed through rDNA biotechnology has been a source of some concern.

Despite the concerns, no unique allergic reactions have occurred to any of the foods derived through rDNA biotechnology. Of course, a consumer with a soybean allergy is likely to be reactive to an rDNA biotechnology-derived soybean as well. But no new and novel allergens have been introduced into foods through rDNA biotechnology. In fact, the proteins introduced into rDNA biotechnologyderived foods to confer traits such as insect resistance and herbicide tolerance are unlikely to be allergenic because they are expressed at very low levels in the modified food, they have no amino acid sequence homology to known allergens, and they are readily digested.

Antibiotic Resistance Transfer. Researchers transferring genes from one plant to another face the challenge of identifying the few cells that have integrated the introduced DNA. This is most often done by introducing a selectable marker that permits growth only of cells containing the newly introduced DNA. In plant transformation, a marker gene for resistance to the antibiotic kanamycin dominated early rDNA biotechnology-derived crops. Concerns were raised about the potential for horizontal gene transfer of the antibiotic resistance gene from an rDNA biotechnology- derived plant to microorganisms, thereby reducing the efficacy of the antibiotic. A joint consultation of the Food and Agriculture Organization and the World Health Organization of the United Nations concluded that there is no evidence that the markers currently in use pose a health risk to humans or domestic animals. The consultation said antibiotic resistance transfer is a rare possibility, but cannot be completely discounted. Furthermore, nonantibiotic resistance markers have mainly replaced kanamycin in products now in the pipeline.

Naturally Occurring Toxicants. Most food plants, and many animals used for food, produce or carry naturally occurring toxic substances. While the vast majority of toxicants occur at levels so low that they carry no threat to human safety, more than 20 have resulted in welldocumented reports of human injury or death from their consumption in or on food. Solanine, a neurotoxin in potatoes, has been the cause of numerous outbreaks of human poisoning when potatoes were grown under unfavorable conditions or when they formed a large part of the diet. Another example is cyanogenic glycosides, found in several foods such as lima beans and bamboo shoots. Given the near ubiquity and occasional demonstrated harm from toxicants that are naturally and unavoidably occurring in most traditional food sources, it is entirely rational to take every reasonable precaution to assure that breeding—by either traditional or rDNA biotechnology methods—does not result in an increase in risk and, if possible, decreases any risk.

L-Tryptophan. L-tryptophan for food and feed use, manufactured by bacterial fermentation, is contaminated by a number of secondary substances. These impurities are removed by treatment with activated carbon and reverse osmosis. A Japanese manufacturer in late 1988 and early 1989 made a number of simultaneous changes in manufacturing, including the use of a genetically engineered organism, Bacillus amyloliquefaciens, to increase production of L-tryptophan. At the same time, the firm altered the purification procedure by eliminating reverse osmosis and reducing the amount of activated carbon used. The illness of 1,500 people and the death of 37 in the United States from eosinophilia-myalgia syndrome from consumption of this L-tryptophan was incorrectly attributed to the rDNA biotechnology-derived organism, rather than to company’s failure to perform standard purification to remove the impurities.

Conclusions

Based on its evaluation of currently available scientific information, the Institute of Food Technologists’ Benefits and Concerns Panel concludes that further development and use of food rDNA biotechnology provides a number of benefits:

  • A more abundant and economical food supply for the world.
  • Continued improvements in nutritional quality, including foods of unique composition for populations whose diets lack essential nutrients.
  • Fresh fruits and vegetables with improved shelf life.
  • Foods with reduced allergenicity.
  • The development of functional foods, vaccines, and similar products that may provide health and medical benefits.
  • Further improvements in production agriculture through more efficient production practices and increased yields.
  • The conversion of nonproductive toxic soils in developing countries to productive arable land.
  • More environmentally friendly agricultural practices through improved pesticides and pesticide usage practices, less hazardous animal wastes, improved utilization of land, and reduced need for ecologically sensitive land such as rain forests.

With regard to a number of environmental and economic concerns about rDNA biotechnology-derived food products, the panel reached the following conclusions:

  • New rDNA biotechnology-derived foods and food products do not inherently present any more serious environmental concerns or unintended toxic properties than those already presented by conventional breeding practices, which have an impressive safety record.
  • Appropriate testing by technology developers, producers and processors, regulatory agencies, and others should be continued for new foods and food products derived from all technologies, including rDNA biotechnology.
  • Programs should be developed to provide the benefits of safe and economical rDNA biotechnology-derived food products worldwide, including in less-developed countries.

In an effort to contribute to a meaningful dialogue on scientific issues and consumer concerns about rDNA biotechnology, the Institute of Food Technologists, a non-profit society for food science and technology, conducted a comprehensive review of biotechnology. IFT convened three panels of experts, consisting of IFT members and other prominent biotechnology authorities, to evaluate the scientific evidence and write a report divided into four sections: Introduction, Safety, Labeling, and Benefits and Concerns.