Chapter 4. Biotechnological Products

Biotechnological Products
  • Economic Aspects

  • Transgenic Animals

  • Transgenics in Agriculture

  • Final Considerations

Some of the common questions of agricultural science during the 1980s and the beginning of the 1990s were these:

  1. Will biotechnology be the solution to world hunger?

  2. Will it substitute for conventional genetic improvement?

For those at the forefront of this new science, these questions resounded with encouragement and challenge. For others who did not feel part of the new science, the questions seemed to threaten conventional methods. These decades have passed and the predictions made then can today be compared in the fields of the farmer.

Although many forums for debate feature people in favor of this technology, many are against its use. The debate about the risks and benefits of this biological technology continues to ignite heated arguments. Various philosophers believe this polarization of society has many beneficial aspects, for it warns scientists of the need to be vigilant in constantly reassessing possible risks.

Although many have made predictions that biotechnology would resolve agricultural problems and end world hunger, some skeptics believed that this science would not be able to generate commercial products that would be competitive in a worldwide market. Perhaps a balanced assessment of the first decades of agricultural biotechnology would show that the predictions from those most optimistic and the most skeptical were both wrong.

Today, society is a witness to the fact that biotechnology develops products and services that have a great impact in the lives of farmers and consumers in many countries. Transgenic varieties of soybeans, corn, cotton, canola, papaya, rice, tomato, and other species have captured the preferences of farmers since the first transgenic variety, the Flavr Savr tomato, was released in May 1994. The agricultural census of 2000 records that worldwide, more than 44 million hectares were planted with transgenic crop varieties, showing a continued increase in the area occupied by these varieties. Soybeans, for example, currently have transgenic varieties planted on 36 percent of the soybean acreage worldwide.

In animal production, the first lines of transgenic species came more slowly. The first animal commercially available on a large scale was the salmon. Transgenic salmon reached American markets in 2001, following rigid evaluations of consumer and environmental safety. Other transgenic animals for food production are in their final steps of development.

Even though many transgenic products are on the market, there is no doubt that biotechnology has neither resolved all of the world's agricultural problems nor abolished world hunger. An understanding of the complexities of agriculture and the factors contributing to world hunger help one understand that biotechnology is only one of the technologies that is able to contribute to the well-being of society. This science constitutes only one part of an integrated solution for the many challenges facing farmers in the production of high-quality food in adequate quantities to meet global demand.

Economic Aspects

Agriculture constitutes a major sector of the global economy. The production and commercialization of food, feed, fiber, and other agricultural products influences the movement of the majority of the world's resources either directly or indirectly. Agribusiness has an impact on the life of all inhabitants of the planet, for no human being is able to feed or clothe himself or herself without agriculture.

The applications of biotechnology in agriculture have a potential market estimated at $67 billion per year. Because of this, it is not surprising that many multinational companies have economic interests in this new science. The competition for this market has motivated these companies to dedicate a great part of their resources to research on and development of new products. Various groups are working on the development of transgenic animals and plants with greater productivity, resistance to diseases and pests, improved nutritional quality, and better tolerance to environmental stresses.

Transgenic Animals

One of the first genetically modified products available for animal production was the bovine somatropin hormone (BST), also called bovine growth hormone (BGH). This hormone is naturally produced in the pituitary gland of the brain. It promotes the growth of young animals and regulates milk production in dairy animals. The genetically modified hormone has been used to increase milk production up to 20 percent in dairy cows. This hormone is produced by transgenic bacteria, in which the bovine gene that codes for BST was inserted into their genome. Therefore, the hormone given to cattle is essentially the same as the one produced in the pituitary gland of the animals.

BST was approved by official organizations of the U.S government and released for use in 1994. Since then, farmers have been able to stabilize milk production in their herds, avoiding inconvenient fluctuations in production levels. Naturally, dairy cows reach peak milk levels around 50 days after calving, after which levels decline during the following 10 months. The use of BST allows the farmer to provide a more constant milk volume.

This technology has provoked debate and worry among many. The public has raised various questions about the economic advantages and risks to both human and animal health. Some consider inducing increased milk production both cruel and harmful to the health of the animal. Although opponents of BST argue that the hormone results in animals with brittle bones, mastitis (an infection of the mammary glands), and decreased resistance to diseases, these problems have not yet been scientifically confirmed. In fact, no known side effects from this hormone to animals or humans have been detected to justify its removal from the market. Another argument against BST is that any risk to human health cannot be measured by tests on short-lived laboratory animals. Only long-term consumption of milk from animals treated with the hormone is able to generate a more conclusive evaluation. Some nongovernmental organizations (NGOs) oppose the use of BST on the basis of ethical principles. These organizations consider it unethical to use a hormone to increase milk production to the maximum limits of production, as if the animals were simply machines.

The U.S. Food and Drug Administration (FDA), an agency that evaluates and authorizes the release of drugs in the country, analyzed questions about the risks of BST to human health. The FDA's conclusion following a detailed study was that the milk and meat from animals treated with BST are safe for human consumption. Today, BST is legally used for milk production in many countries around the world.

The lack of evidence against BST and its increased use in different countries has caused NGOs to change their tactics. Instead of proposing a ban on the use of the hormone, their strategy has shifted to support the labeling of milk produced with BST.

Among the promises of biotechnology in this area are genetically modified cows that produce, in their own glands, a greater quantity of BST, thereby eliminating the need to give the hormone to animals during lactation.

Especially in animal production, biotechnology can contribute to improvements in the quality of meat, milk, eggs, and wool, as well as disease resistance in animals, which would serve to reduce the use of antibiotics in production processes. As mentioned earlier, salmon was the first transgenic animal approved for human consumption. This animal possesses an additional gene that codes for a growth hormone that allows the fish to grow more rapidly because of an improved food conversion rate, which is 15 percent greater than it is in nontransgenic salmon (Figure 4-1).

Genetically modified salmon, the first transgenic animal for food production.

Figure 4-1. Genetically modified salmon, the first transgenic animal for food production.

The transgenic salmon were obtained through genetic transformation of the sperm from male fish, which were then used to fertilize the female eggs, thereby producing a transgenic zygote (Figure 4-2). The primary methods of reproductive cell (sperm and egg) transformation in fish are electroporation, microinjection, and biolistics (see Chapter 3, “Transformation”).

Production of transgenic fish.

Figure 4-2. Production of transgenic fish.

It is predicted that within a few years, there will exist transgenic lines of poultry, producing eggs that will have a lower content of cholesterol; cows producing milk with lower lactose levels, which is extremely important for some ethnic groups; lines of sheep with longer and stronger wool fibers; and more. Although animal breeding has been able to make substantial progress for some of these traits, some of the promises might only be realized with the help of biotechnology. One example is pork production, where fat content must be reduced. Biotechnology might be the best way to significantly reduce fat. This is especially important when the desired trait is not present in other animals of the same species or in species that are sexually compatible. Biotechnology allows the transfer of genes, and therefore traits, among different species.

Actually, there are transgenic lines of sheep, goats, and swine with different transgenic traits in the final phases of evaluation. These animals might be useful, not only for food production, but also as “bioreactors” in the production of hemoglobin and antibodies to combat snakebites, as well as other applications in pharmaceuticals, nutrition, and the production of tissue and organs for human transplants. For example, during the 1980s, some hemophiliacs were infected with the AIDS virus because blood banks failed to test donors for HIV. Although the blood banks continued the use of human blood, two problems became evident: the problem of reduced donations not meeting the growing demand, and the risk of transmitting contagious diseases for which testing had not been developed. One project that seeks to address these problems is the development of transgenic swine that produce human plasma and hemoglobin. Presently, there is no evidence of HIV in swine, making them potential blood donors. Even so, tests are being done to learn about the possible transmission of other diseases and viruses in swine to humans.

Transgenic Animals as a Source of Organs and Tissue

Xenotransplant, or tissue or organ transplant among different species, genera, or families, has been indicated as one possible solution to the shortage of donor organs. A common example of xenotransplant in use today is the use of swine heart valves in humans (see Figure 4-3). An additional problem with transplantation is rejection. When cells or tissue from an individual are transplanted to another individual, the recipient recognizes the transplanted tissue as being foreign (an antigen). This begins the production of antibodies that attack the antigen, causing rejection of the organ. This situation could be remedied with the use of transgenic animals.

Development of transgenic animals for xenotransplant.

Figure 4-3. Development of transgenic animals for xenotransplant.

With the aging of the population, the number of patients needing organ transplants has been increasing significantly, but the number of donors has been growing only moderately. In spite of the preventive campaigns that emphasize the importance of controlling blood pressure and cholesterol levels, maintaining a balanced diet, and eliminating sedentary habits and cigarette use, cardiovascular diseases continue to kill four times more people than AIDS, and three times more people than breast cancer. A more effective therapy for many heart disease patients is the use of organ or tissue transplants. Approximately 45,000 Americans under age 65 could benefit from a heart transplant, but only 2,000 human hearts are annually available for transplant in the United States.

Xenotransplantation might eventually be used not only for heart patients, but also for the treatment of kidney diseases, diabetes, Parkinson's disease, Alzheimer's disease, and even in the treatment of third-degree burn victims.

Recently, scientists have created genetically altered pigs with a gene involved in the rejection of transplanted organs. Although this is still an experimental procedure, xenotransplants are extremely promising from the perspective of the great demand and limited availability of organs, and the resultant patient waiting lists.

The first transgenic pigs (Figure 4-4) developed for xenotransplants by PPL Therapeutics in December 2001 have the gene alpha 1,3 galactosyl transferase silenced. This gene codes for an important enzyme in sugar metabolism in the swine's cell membrane.

Transgenic pigs developed for xenotransplant.

Figure 4-4. Transgenic pigs developed for xenotransplant.

Swine have received the most attention from scientists in the field of xenotransplantation because they are so biologically similar to humans and they are not carriers of human diseases. Primates, although genetically more similar to man, involve additional risks in the transplant cases because they are known carriers of human diseases.

Some scientists, however, are aware of the indirect risks of xenotransplantation. This technique might transfer viruses or other infectious microorganisms from animals to humans. One example is the porcine endogenous retrovirus (PERV), a virus that has evolved with swine but does not cause disease. It is not known, however, what might happen if these nonpathogenic viruses were introduced into humans through transplanted organs. Additionally, ethical issues have also been raised concerning the implications of people using animal parts in organ or tissue transplants.

Transgenics in Agriculture

The world population reached 6 billion in 2000; this signifies a doubling of the population in the last 40 years. There is no global initiative to reduce population growth, and the expectation is that the world population will reach 9 billion inhabitants around the year 2040, generating a 250 percent increase in demand for food.

An increase in food production might come from the following three areas:

  1. Adding new land to production. This option is extremely unlikely or even impossible in many developed countries where all available land is being used for agriculture. In the United States, Brazil, and a few other countries, the expansion of agricultural frontiers is still possible where large tracts of native land still exist, but are not currently being exploited. However, this poses the threat of significant harm to the environment.

  2. Reducing losses, whether they are caused by pests or diseases, or from cultivation or harvesting problems. The losses from transportation and storage also contribute to waste of food.

  3. Increases in crop productivity.

Biotechnology can contribute in each of these three areas to increase food production. In what has been said about expanding agricultural frontiers, biotechnology can contribute crop varieties with more tolerance to drought or poor soil conditions. Pests, diseases, and weeds not only reduce agricultural productivity; they also contribute to increased production costs, as they require farmers to apply agro-chemicals. Another inconvenience associated with agro-chemicals is the environmental pollution and chemical residues on produce. There exist about 40,000 species of microorganisms that cause diseases in plants and approximately 30,000 species of weeds that compete with crops for nutrients, water, space, and light, causing additional reductions in productivity. The first transgenic plant variety produced on a large scale was developed to assist in the control of weeds, as is the case in soybeans resistant to the herbicide glyphosate.

Varieties Resistant to Herbicides

The difficulty in controlling weeds through the application of herbicides is that there is no single chemical product designed for broad-spectrum weed control that does not cause injury to the crop. Normally, when an herbicide is effective in controlling weedy grasses, it is not effective on broadleaf weed species. The development of crop varieties tolerant to herbicides has been a major focus for biotechnology companies. Today there are varieties of various crop species with resistance to nonselective herbicides, or herbicides that kill all types of plants.

The idea of developing crop varieties with tolerance to herbicides came from an observation that some weeds acquired tolerance to some chemicals after repeated sprayings. Scientists found that some herbicide-resistant weeds or even bacteria have altered enzymes or other mechanisms to inactivate the herbicide. This information led to research on using biotechnology to transfer the modified enzymes to crops, which confers resistance to the herbicide. Monsanto developed the first transgenic varieties tolerant to herbicides. These varieties are known as Roundup Ready, as they are resistant to the herbicide glyphosate, which has the trade name Roundup. Glyphosate blocks the synthesis of the aromatic (ringed) amino acids by binding and inactivating the enzyme EPSPS, which is essential in the synthesis of these amino acids in plants. Roundup Ready crop varieties include a gene that codes for an altered form of the EPSPS enzyme that has less affinity to the herbicide, but is still able to catalyze reactions and synthesize aromatic amino acids. The gene for resistance to glyphosate has already been introduced into many crop species of economic importance beyond soybeans.

Farmers have shown a great interest in planting Roundup Ready varieties because they allow for more efficient and economic weed control with application of only one herbicide. With the use of one herbicide to control the majority of weeds, farmers can reduce the number of herbicide applications needed for effective weed control.

Considering that varieties tolerant to herbicides would reduce the amount of chemicals applied to the land, they should also be preferred by consumers. However, a lack of communication about the advantages of these varieties not only for the farmer, but also for the environment and consumers, has divided public opinion, creating questions about the safety of these crops. Even though these varieties, as with any other genetically modified organisms, pass through stringent biosafety evaluations that analyze the risks to human and animal health and to the environment (tests of environmental impact), many people continue to be skeptical about the benefits of transgenic crops.

Crop Varieties Resistant to Insects

One of the most effective biocontrol agents is the bacterium Bacillus thuringiensis (Bt). This bacteria has been used in the control of caterpillars in fields since 1980, when it was discovered that the bacteria produces a protein that is toxic to the lepidoptora species of insects, which includes caterpillars. When caterpillars eat plant leaves on which the bacterial spores have been deposited, the bacteria grows in the digestive tract and a protein-like crystal is produced (Bt protein). The protein basically attaches to cellular membranes of the caterpillar's digestive system, altering osmotic potentials and eventually killing the insect. The digestive system in mammals, including humans, produces an acid that rapidly degrades the Bt protein if it is ingested, making it harmless to human health. The Bt insecticide has been considered one of the safest chemicals to man and the environment. Because of its effectiveness, scientists wanted to create transgenic plants that were able to express the Bt protein.

This gene has been transferred to varieties of corn, cotton, tobacco, potato, and other species to extend the control of caterpillars. Bt crop varieties synthesize the Bt protein in their own tissue. After eating plant matter (leaves, stems, etc.) from Bt varieties, caterpillars die within two days. This has dramatically reduced the amount of insecticide needed to control the insect in crops.

However, some people still prefer to use products from conventional corn, produced under an intense program of chemical insecticide applications, instead of those obtained from Bt corn.

One of the worries with the use of Bt corn is the development of resistance within the insect population and a subsequent loss of efficacy in pest control with the Bt protein. Because a plant is continually producing the Bt protein in its tissues, there is an increased chance that insect populations will develop resistance. To address these potential problems, farmers who adopt this technology are required to implement a resistance management plan that establishes a refuge area where the insects can reproduce and feed on conventional plants that do not produce the Bt protein. Additionally, farmers are encouraged or, at times, requested to have a rotation of conventional cultivars with the genetically modified cultivars. These practices reduce the selection pressure on the insects, thereby reducing the likelihood of resistance developing in the population.

Plant Varieties for the Production of Bioplastics

Biotechnology has the potential to improve not only food production, but also nonfood products such as plastic (see Figure 4-5). Plastics are long polymers based on organic compounds. Although the major component of plastic has petroleum as its primary material, it can also be synthesized in plants. Currently, an interesting project is underway at the University of Minnesota aiming to develop transgenic crop varieties for bioplastic production. The bacteria Alcaligenes eutropus handles the production of polyhydroxybutyrate (PHB), a biodegradable and renewable biopolymer (independent of petroleum). The gene from A. eutropus that codes for an enzyme responsible for the biosynthesis of PHB is being transferred to corn, a species highly efficient in biomass production, which will contribute to reductions in the production costs of this biodegradable plastic. Obtaining transgenic species with an elevated expression of this gene would certainly make biodegradable plastic more competitive in the marketplace.

The replacement of plastic derived from petroleum with bioplastic would reduce environmental pollution.

Figure 4-5. The replacement of plastic derived from petroleum with bioplastic would reduce environmental pollution.

Corn is a highly productive and efficient plant species. Consider the case of cornstarch, which is produced at a similar cost to petroleum for each unit of energy generated. However, contrary to petroleum, plant-based energy sources are renewable and more environmentally friendly. Through engineering the genes that code for cornstarch, it is possible to produce starch with different properties. For example, scientists are developing an edible bioplastic that would allow foods to be cooked in their own packaging, thereby reducing the volume of domestic waste.

Plants and Animals as Bioreactors

Rural enterprises will undergo substantial changes in the coming decades. Grain collected in the field, milk from cows, and eggs produced from chickens will probably have other fates than merely serving to feed the population. Genetic engineering will produce varieties of plant species and lines of animals that will function as bioreactors, or living factories for the production of pharmaceuticals, chemical products, plastics, fuel, and other products. Because of this, farms will stop being only a source for food.

Plants already produce a variety of chemicals used by industry for production of medicines (Pilocarpus pinnafolius), dyes (Bixa orellana), paint (soybeans), and industrial oils (canola). The introduction of new genes could alter the quality and quantity of existing products. For example, altering the composition of fatty acids in legumes such as soybeans, canola, and peanuts, it is possible to develop different types of oils that can be used for healthier diets for people with cardiovascular diseases or for the production of hydraulic fluids for automotive and industrial uses.

A curious example that is still found in studies is the production of anticoagulants in the canola plant. In this project, scientists isolated genes that code for the production of anticoagulation factors from a leech, which were then transferred to canola. This anticoagulation factor is synthesized by the plant and stored in the seeds, allowing relatively easy extraction and purification of the factor. These anticoagulants have important applications in the treatment of circulatory diseases.

Cattle, swine, sheep, and poultry have been genetically modified to produce different proteins with applications to human health. This form of protein production introduces a series of advantages over traditional methods, including lower costs and reduced risks of contamination. The use of tissue-specific DNA promoters, meaning promoters that activate transgenes only in the desired organs or tissues, reduces the risks of side effects for the transgenic animals. For example, the use of a promoter that only expresses a transgene in the mammary glands induces the animal to deposit the protein in the milk, thereby simplifying collection and purification.

Another example is the production of antibodies. An egg yolk normally contains antibodies that are deposited by the hen to protect the embryo from infections in the period preceding the development of its immune system. The types of antibodies deposited can be modified through immunization with specific antigens. With transgenic poultry there is no need to immunize the birds for the production of eggs with antibodies to combat diseases of other animals, including humans.

Finally, transgenic animals developed for pharmaceutical studies also have great importance. For example, a line of transgenic mice in which researchers inserted an oncogene (a gene related to cancer formation) was the first animal to be patented. Researchers have used these mice to study different cancer treatment therapies. However, the first transgenic monkey was obtained with the introduction of the GFP gene, by way of a retrovirus (Figure 4-6). This animal has been named ANDi, an acronym for inserted DNA, written backwards. ANDi has been important in more advanced biological and genetic studies.

ANDi, the first transgenic monkey obtained in the Primate Research Center in Oregon.

Source: Courtesy of Oregon Health and Science University.

Figure 4-6. ANDi, the first transgenic monkey obtained in the Primate Research Center in Oregon.

Final Considerations

Transgenic products are already available in many countries. Defenders of biotechnology have emphasized the benefits of these products to society. The potential realized to this point is only a small glimpse in relation to what will be realized in the near future. However, those opposed to biotechnology have presented a list of concerns that have strong appeal to society. Some of the arguments against transgenics include the following:

  • It only serves the interests of large corporations.

  • It does not favor sustainable agriculture.

  • Biotechnology only benefits large farmers.

  • It creates dependence on other products and services from large multinational companies.

Amidst these critics, the scientific world hopefully awaited a product of genetic engineering that would not be the target of any of these arguments. Finally in 2000, the Swiss Institute of Crop Science in Zurich, a governmental agency, released a transgenic rice variety dubbed Golden Rice. This rice (Figure 4-7) rapidly gained the sympathy of society and attracted international media attention. This transgenic variety was the result of work by a group of Swiss and German researchers, through funding from the Rockefeller Foundation, the European Community, and the Swiss Institute of Technology. Golden Rice consists of rice lines that have elevated levels of β-carotene, a precursor to vitamin A. Within this rice plant, the biochemical pathway for β-carotene was engineered by inserting genes from the daffodil (Narcissus pseudonarcissus) and a fungus (Erwinia uredovora). This rice variety was developed to help combat blindness resulting from a deficiency of vitamin A, a critical problem in less developed countries, such as some in Africa and Southeast Asia.

Grains of Golden Rice, rich in β-carotene.

Source: Courtesy of Swapan Datta, International Rice Research Institute (IRRI).

Figure 4-7. Grains of Golden Rice, rich in β-carotene.

With general approval from the public, even the less optimistic organizations, notably those critical of genetically modified organisms (GMOs), were expected to approve the arrival of Golden Rice. To the surprise of many, some NGOs are trying to prevent Golden Rice from being made available to the small farmers of countries where vitamin A deficiency blindness is a major problem. Golden Rice was not developed by a multinational company, does not require the use of other agro-chemicals, was not developed for large farmers, and is not incompatible with sustainable agriculture. How is it possible that this product could arouse so much opposition? Unless these organizations are failing to exercise their critical senses, how can one understand such rejection amidst the reality from UNICEF data showing that 1 million to 2 million deaths could be avoided annually if a vitamin A supplement were available? Additionally, 1,369 children lose their vision daily because of vitamin A deficiency. Many still question why there has been so much opposition to the release of a product with such humanitarian potential.

It is utopian, however, to think it possible to have reconciliation between groups with such contrasting ideologies. It would be irresponsible to argue that all the biotechnological products represent only benefits without risks. It is important that society, with its many forms of expression, including NGOs, should be vigilant and question technological advancements. Even with ideological differences, there exist common objectives among all people, an example being the production of abundant food with high nutritional quality at accessible prices with minimum damage to the environment. Although it might be true that businesses envision as a priority products that bring them economic return, it is also true that they are aware that society will not tolerate products that are harmful to the environment or human health. Although environmentalists consider the multinational companies their enemies, they are blind to the fact that these companies are also allies in the search for alternatives and solutions to the problems facing humanity.

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