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A.3 Types of biotechnology
Agricultural biotechnology

A brief history

Agricultural biotechnology is usually dated back to 10,000 BC when farmers began to select the most suitable plants and animals for breeding (see Table 1). Soon thereafter, Sumerians used yeast, a type of fungus, to make beer and wine in Mesopotamia. As the plant breeding process became better known, farmers and early plant breeders would look for varieties with useful characteristics that could be crossed with other varieties to produce offspring that combined the characteristics of both. In the 1860s, Gregor Mendel methodically recorded the passing of traits from one generation to the next by crossing different pea plants to produce offspring with red or white flowers, and wrinkled or smooth peas. He identified the principles of inheritance and marked the beginning of conventional agricultural biotechnology. Major advances in plant breeding followed the revelation of Mendel’s discovery. Breeders brought their new understanding of genetics to the traditional techniques of self-pollinating and cross-pollinating plants.

Recognising desirable traits and incorporating them into future generations is very important in plant breeding. A few of these traits can arise spontaneously through a process called mutation, but the natural rate of mutation is very slow and unreliable to produce all plants that breeders are looking for. In the late 1920s it was discovered that exposing plants to x-rays and chemicals could increase the rate of genetic variation, thereby increasing the pool of characteristics that breeders and farmers could choose from when looking for beneficial features for crop breeding. ‘Mutation breeding’ accelerated after World War II, when the nuclear age’s techniques became widely available. Examples of plants that were produced via mutation breeding include varieties of wheat, barley, rice, potatoes, soybeans and onions.

However, the new varieties that result from conventional breeding have a number of limitations. The characteristics may not be consistent from generation to generation, as in the case of hybrid crops. Hybrid seeds are developed by crossing parent lines that are ‘pure lines’ produced through inbreeding. Pure lines are plants that produce sexual offspring that closely resemble their parents. By crossing pure lines, a uniform population of first generation hybrid seed can be produced with predictable characteristics. However, if the seeds of the first generation hybrids are used for growing the next crops, the resulting plants do not perform as well as the first generation material, resulting in inferior yields and vigour. Also, in conventional breeding, only varieties able to sexually reproduce with one another can share genes, thereby preventing for example the transfer of a useful characteristic of a variety of maize to cassava. Moreover, it can be difficult to select the characteristics that are of interest from two plants during the reproduction process. While the offspring that result will have characteristics from each parent, a key problem of hybrid breeding – and conventional biotechnology in general – is that genes are transferred randomly from the parents to the new variety.

Modern biotechnology is the latest stage in the development of plant breeding technology. Crick and Watson’s discovery of DNA’s double helix structure in the 1950s held the key to cracking the genetic code that determines the characteristics of all living organisms. As a result, techniques such as genetic modification enabled plant breeders to transfer solely the gene of interest and allowed them to choose genes not only from related varieties but from any organism. As a result, desired genes can be transferred more quickly than through the time-consuming variety-crossing process entailed in conventional biotechnology, while avoiding the uptake of unwanted characteristics.

Table 1: An agricultural technology timeline

Technology
Era
Genetic interventions
Traditional
About 10 000 years BC Early farmers domesticated crops and animals from available biodiversity, began to select plant materials for propagation and animals for breeding
About 3 000 years BC Beer brewing, cheese making and wine fermentation
Conventional
Late nineteenth century Identification of principles of inheritance by Gregor Mendel, laying the foundation for classical breeding methods
1930s Development of commercial hybrid crops
1940s to 1960s Use of mutagenesis, tissue culture, plant regeneration. Discovery of transformation and transduction. Discovery by Watson and Crick of the structure of DNA. Identification by Barabara McClintock of genes that detach and move (transposons)
Modern
1970s Advent of gene transfer through recombinant DNA techniques. Use of embryo rescue and protoplast fusion in plant breeding and artificial insemination in animal reproduction
1980s Insulin as first commercial product from gene transfer. Tissue culture for mass propagation in plants and embryo transfer in animal production
1990s Extensive genetic fingerprinting of a wide range of organisms. First field trials of genetically engineered plant varieties in 1985 followed by the first commercial release in 1994. Genetically engineered vaccines and hormones and cloning of animals, marker-assisted breeding
2000s Bioinformatics, genomics, proteomics, metabolomics, gene silencing (iRNA)


The science behind genetic modification

The differences that distinguish one organism from another are encoded in its genetic material – its DNA. The DNA occurs in pairs of chromosomes, one coming from each parent. The genes, which control the organism’s characteristics, are specific segments of each chromosome. All of the organism’s genes together make up its genome. Some genes may be relatively unimportant while others may determine, for example, the length of time it takes for a crop to come to harvest or the extent to which an animal is resistant to disease. As scientific understanding of DNA has increased through the development of the field of genetics, it has become possible to identify many of the genes that confer specific characteristics on an organism. It is also now possible to insert that gene into another organism.

Modern genetic modification involves five steps (Hain and Ehly, 2005):

  1. DNA extraction: The relevant DNA is extracted from the desired organism by taking the organism containing the gene of interest through a series of steps.

  2. Gene cloning: The gene has to be cloned or mass-produced to make thousands of copies.

  3. Gene design: This step is particularly important. The gene has to be ‘packaged’ with two other pieces of DNA that control how the gene will work once it is inside its new organism. The first piece, called a ‘promoter’, is attached and controls whether the gene is switched ‘on’ or ‘off’ all the time, some of the time, or none of the time. The second piece, called a ‘marker gene’, is also attached to the gene of interest so that scientists can efficiently test whether the gene, and so the desired characteristic, has been transferred. Typically, this marker gene will confer resistance to a selectable agent, such as an antibiotic or a herbicide. Thus, only the cells containing the construct (i.e. the gene of interest and the marker gene) will survive or continue to grow after treatment with the selectable agent. Alternatively, a marker for screening can be used that will make the cell containing the gene look different, such as a colour marker.

  4. Transformation: The gene package is inserted into the cells of the organism being modified using either a gene gun or a bacteria called Agrobacterium.

  5. Backcross breeding: The genetically modified organism is crossed with the best varieties of conventional crops in order to get a variety that has the best characteristics that conventional crops and genetic modification can deliver.

Figure 1: The science of genetic modification

Adoption of genetically modified crops

Transgenic crops were first commercialised in 1994. Since then, the global area of transgenic crops has increased from 2.8 million hectares to 90 million hectares (see Figure 2). The annual growth rate of the global area of approved biotech crops was very high in 1997 and 1998 at 357 percent and 117 percent respectively. In recent years, growth rates have fluctuated around 15 percent.

Ín 2005, 8.5 million farmers in 21 countries planted biotech crops, approximately 75 percent of which were grown in industrialised countries. The countries include the US, Argentina, Brazil, Canada, China, Paraguay, India, South Africa, Uruguay, Australia, Mexico, Romania, the Philippines, Spain, Colombia, Iran, Honduras, Portugal, Germany, France and the Czech Republic. The global market value of biotech crops was US$ 5.25 billion. The value of the global biotech crop market is based on the sale price of biotech seed plus any technology fees that apply (James, 2006). Soybeans, maize, cotton and canola are the four main GM crops, with 54.4, 21.2, 9.8 and 4.6 million hectares respectively planted of each crop worldwide in 2005.

The two main biotechnology traits are herbicide tolerance (71 percent of total plantings) and pest resistance (18 percent). Herbicide-tolerant plants have been genetically modified to survive the spraying of a particular herbicide, usually by inserting a gene from the soil bacterium Agrobacterium tumefaciens that enables them to survive treatment from glyphosate, a pesticide that can eradicate most weeds in one application. By enabling farmers to apply a single treatment of glyphosate to control weeds, herbicide resistance aims to reduce the frequency of application and quantities of chemicals, and allow for the use of chemicals with lower toxicity and persistence in the soil (FAO, 2004). Roundup Ready® soybeans, developed by Monsanto, are by far the most popular herbicide-tolerant crop. Grown in the US, Argentina, Brazil, Paraguay, Canada, Uruguay, Romania, South Africa and Mexico, they represent 60 percent of the global biotech crop area of 81 million hectares for all crops (James, 2006).

Figure 2: Growth rates for the global area of transgenic crops (1996-2005)

Source: Adapted from the International Service for the Acquisition of Agri-biotech Applications (ISAAA), www.isaaa.org

Figure 3: Location of legally planted GM crops in 2005 (percentage of global coverage)

Source: James (2006)

Figure 4: Global area of legally planted GM crops in 2005 by crops (percentage)

Source: James (2006)

Commodity crops, such as maize, cotton, soybeans and canola, have also been genetically engineered for resistance to pests. When introduced into plants, a gene from the common soil bacterium Bacillus thuringiensis (known more simply as ‘Bt’) generates a protein that, when eaten by the target species, kills insect larvae and particularly caterpillar pests. Bt is harmless to humans, pets and most beneficial insects such as bees, and has been used for many years in insecticide sprays. Bt maize is the most popular insect-resistant crop, occupying 11.3 million hectares, equivalent to 14 percent of global biotech area in fields in nine countries: the US, Argentina, Canada, South Africa, the Philippines, Spain, Uruguay, Honduras, Portugal, Germany, France and the Czech Republic. Bt cotton is also widely used, covering 4.9 million hectares, equivalent to five percent of global biotech area, in China, India, Australia, the US, Mexico, Argentina, South Africa and Colombia (James, 2006).

Most of the GMOs commercialised in developing countries to date have been acquired from developed countries and focus on a limited number of traits (herbicide tolerance and insect pest resistance) and crops (commodities such as cotton, soybean, canola and maize). Efforts are also being made to develop GMOs with traits that address the needs of developing countries more specifically (see Q7). Several developing countries, headed by Argentina, Brazil, China, Cuba, Egypt, India, Mexico and South Africa, have been conducting research on a wider range of crops, such as banana, cassava, cowpea, plantain, rice and sorghum, and on traits such as abiotic stress tolerance that would allow crops to grow in salty soils or in dry areas. Research has also focused on developing crops that produce medicines or food supplements directly within the plants.

GM crops with improved agronomic traits have been categorised as ‘first generation’ biotech products. A shift in focus is expected with the transition from the first to the ‘second generation’ of GM crops, which in addition to new agronomic traits also incorporate enhanced quality traits, such as improved nutritional value of food and feed. Many of these new traits have already been developed by public, private and public-private partnership initiatives but have not yet been released on the market. Applications under development include soybeans with higher protein content; rice engineered to produce ß-carotene, and crops with modified oils, fats and starches to improve processing and digestibility. The success of the second generation of GM crops will ultimately depend on their profitability at the farm level and their acceptance by consumers (FAO, 2004).

Other forms of agricultural biotechnology

There are many kinds of biotechnology beyond genetic modification that find application in agriculture. For instance, marker-assisted selection uses genotypic information obtained through DNA testing (or ‘genetic fingerprinting’) to assist in the selection of suitable individuals to become parents in the next generation. Biotech critics (e.g. Rifkin, 2006) have hailed this technology as a viable alternative to genetic modification by allowing breeders to speed up natural plant and animal breeding programmes without the need for genetic modification. The International Centre for Tropical Agriculture (CIAT), for example, is using marker-assisted selection to develop a cassava variety with high contents of carotene, protein and dry matter as well as high resistance to cassava mosaic disease (CIAT, 2001). Molecular-assisted selection also provides a faster and more accurate tool for backcrossing – the final stage of genetic modification.

Other techniques include tissue culture and micropropagation, which involves taking small sections of plant tissue, or entire structures such as buds, and growing them under sterile conditions on specially selected media containing substances essential for growth with the objective to regenerate complete plants. This technique is particularly useful for maintaining valuable plants, breeding otherwise difficult-to-breed species (such as many trees), speeding up plant breeding and providing abundant plant material for research. Micropropagation can also be used to generate disease-free planting material (FAO, 2004). The technique is relatively cheap and has been shown to increase general productivity.

The most common application of tissue culture in developing countries involves producing virus-free plantlets by heat-treating the tissue plant to kill any viruses present and then culturing cells from the plant’s actively growing tissue. In Kenya, for instance, banana shoot tips have been heat-treated to destroy diseases and then reproduced in tissue cultures through micropropagation, creating as many as 1,500 new disease-free banana plants. In China's Shandong Province, micropropagation enabled the creation of virus-free sweet potatoes which led to an increase in yields of up to 30 percent. These productivity increases raised the agricultural income of the province's seven million sweet potato growers by three to four percent in one season (Fuglie et al., 1999). In Uganda, a company uses tissue culture to produce pathogen- and pest-free plantlets which are being distributed through nurseries and demonstration gardens set up in different areas of the country (Nsubuga, 2006).

The use of diagnostic tests to fight plant diseases is another type of non-GM biotechnology. Molecular assays such as enzymes-linked immunosorbent assay (ELISA) can precisely identify viruses, bacteria and other disease-causing agents. ELISA has become an established tool in disease management in many farming systems and is now the most widely used commercial diagnostic technique in all regions of the developing world (Dhlamini, 2006).

Also, products based on micro-organisms play an increasing role in pest control and soil enrichment, including ‘biopesticides’ (i.e. pesticides derived from natural materials which are more selective, less toxic to humans and the environment and more effective at lower rates of application than conventional chemical pesticides), ‘biofertilizers’ and products that aid fermentation and food processing. While research in these products is in the early stages in Africa and Asia, developing countries such as China, India and the Philippines are already using advanced techniques. Studies on biofertilizers, mainly Rhizobium, are currently being carried out in many developing countries.

Industrial biotechnology

Industrial biotechnology (or ‘white biotechnology’) covers two areas, namely (1) the use of biological systems such as cells or enzymes (used as reagents or catalysts) to replace conventional, non-biological methods, and (2) the use of renewable raw materials (biomass) to replace raw materials derived form fossil fuels (Juma and Konde, 2005). Biotechnological processes are being widely applied in the chemicals industry (especially for fine chemicals and pharmaceuticals), pulp and paper production, textiles and leather, food processing (including animal feed), metals and minerals and the energy sector (OECD, 1998; OECD, 1999). They can be used to create new industrial supplies (biochemicals, enzymes and reagents for industrial and food processing); environmental elements (pollution diagnostics, products for pollution prevention and bioremediation); and energy.

Although industrial biotechnology is not ‘clean’ per se, it offers potential environmental benefits, such as reduced resource consumption and waste generation. Detergent enzymes, for example, such as protein-removing enzymes, can cut phosphate release into the environment and energy use during washing. Biotechnology is also used for processing pulp and paper to reduce energy use and extract more value from the resource. Driven largely by market and environmental demands for less chlorinated products and by-products, the pulp and paper industry is cited as the fastest-growing market for industrial enzymes.

One interesting biotechnology application in the chemicals sector is the use of plants as finished products to produce plastics. Monsanto, for example, has experimented with a genetically modified cress variety to produce a biodegradable plastic using a gene extracted from a bacterium, Ralstonia eutropha. Other applications include the production of bio-based polymers. Cargill Dow LLC, for instance, has commercialised NatureWorksTM – polymers derived entirely from annually renewable resources, such as maize. The polymers, which are used to produce clothing, packaging materials and electronic goods, are claimed to require 25 to 55 percent less fossil resources to produce than comparable petroleum-based plastics (EuropaBio, 2003).

Biotechnology is also becoming increasingly important in the manufacture of textiles, for instance to produce fibres derived from natural substances such as lyocell, rayon and cellulose acetate (OECD, 1998). Other examples include fibres with improved or novel features, such as genetically engineered cotton containing a bacterial gene that makes a polyester-like substance, resulting in fibre that has the texture of cotton, but is much warmer. Companies such as Monsanto, Calgene, Agricetus, DuPont and Bayer are investigating possibilities of engineering cotton for increased strength, improved dye uptake and retention, enhanced absorbency and wrinkle- and shrink-resistance. Transgenic approaches could also increase the colour range of cotton. In the area of animal-derived fibres, genetic studies on sheep and goats are being carried out in Australia and elsewhere with the objective of producing fibres that are insect- and pest-resistant, softer, finer and more easily harvested.

Among food biotechnology applications, production of basic food ingredients (proteins, carbohydrates and fats) from non-traditional sources is theoretically possible using microbial fermentation or plant tissue culture. Also, consumer preferences for ‘natural’ food additives (including gums, emulsifiers, vitamins, minerals and preservatives) give biotechnology-derived products an advantage over chemically-synthesised ones, if their cost is competitive. The use for plant tissue culture for the production of natural flavours such as vanilla has also been suggested as a promising application (OECD, 1999).

Biotechnology has also been applied in the energy sector (OECD, 1998). It has improved the overall efficiency of processes, particularly in the area of pollution control. Processes and products currently under development, such as biodiesel, bioethanol and biodesulphurisation, aim to replace systems that are more energy-intensive and generate less benign by-products, for instance by replacing fossil fuels with renewable raw materials.

However, despite its potential, the widespread application of industrial biotechnology continues to face a number of challenges (OECD, 1999). Novel processes require capital expenditure and development costs, which can be higher than the costs of using traditional mechanical or chemical processes. As a result, significant investments in industrial biotechnology have been limited to industrialised countries and large developing countries. However, intermediate developing countries with existing industries and some scientific capacity could benefit from applying biotechnology to industrial processes, most notably in cleaner production processes. The Organisation for Economic Co-operation and Development (OECD), for example, has suggested that using industrial biotechnology for fuels and for creating more environmentally-friendly chemicals can reduce the environmental footprint of industrialisation while also reducing costs (OECD, 2001).

Medical biotechnology

The field of medical biotechnology continues to expand rapidly, offering new tools for the diagnosis and treatment of many diseases and inherited disorders. The Human Genome Project, which has mapped the approximately 20,000-25,000 genes in human DNA, has greatly contributed to advances in this field. The mapping has provided a framework to identify each human gene and the specific role(s) it performs. This map can then be used in a variety of ways, including diagnosis of genetic disease, preventative health care and gene therapy.

Biotechnology can contribute to diagnosis by looking at a patient’s genes to assess the susceptibility to illnesses (Biotechnology Australia, 2006). Where a disease is known to be caused by one or a few genes (such as cystic fibrosis), or an extra chromosome (such as Down syndrome), genetic testing can help diagnose disorders before patients have developed symptoms. The technique can also be used to discover if a foetus has a genetic disorder. Moreover, reading the DNA of individual humans can help people who carry the genes linked to diseases such as breast cancer, diabetes or osteoporosis to undertake preventative measures, such as more frequent health checks or adapting their diet and lifestyle.

Another technique – gene therapy – involves the introduction of a healthy gene into a cell to replace a disease gene. Unlike conventional treatments which attempt to deal with the consequences of a defect, gene therapy aims to correct the defect itself. To this end, researchers isolate normal DNA and package it into a vector, such as a virus. Doctors then infect a target cell – usually from a tissue affected by the illness, such as the liver or the lungs – with the vector. The vector ‘unloads’ its DNA cargo, which then begins producing the missing protein and restores the cell to normal.

Medical biotechnology has also assisted in the development and production of new drugs, including antibiotics and specific compounds, such as interferon alpha to treat hepatitis C and cancer. By studying the genetics of viruses such as HIV/AIDS, fungi and bacteria that infect humans, scientists can understand how they cause disease and develop drugs that target them more specifically. Vaccines can also be developed using a fragment of the microbial DNA which will produce the antigenic protein directly in the body and may induce the immune system to produce antibodies.

Plant genetic modification can also serve medical purposes. For example, plants can be genetically modified to produce substances that can be refined into processed compounds used in pharmaceuticals. Plants can also be modified to produce vaccines that can be administered by eating the produce. However, both types of GM applications are relatively controversial and pose high regulatory demands.

Animal biotechnology

Biotechnology is also used for developing animal vaccines and medicines, cloning and the genetic modification of animals and insects. Other applications include improving animal health and performance, increasing livestock and poultry productivity, and using animals for the production of pharmaceuticals.

Biotechnology-based processes to produce animal vaccines are becoming more common and many regulators and animal breeders hope that they will provide more effective, safe and inexpensive vaccines to safeguard animal health. These new and improved medicines for animals help lower production costs and fight diseases caused by bacteria and parasites. Vaccines are used to prevent diseases, including foot and mouth disease, scours, brucellosis, shipping fever, feline leukaemia, rabies and infections affecting cultivated fish (Vines, 2002).

Animal biotechnology also includes techniques to enhance reproduction and breeding methods such as artificial insemination and multiple ovulation/embryo transfer (MacKenzie, 2005). In addition, an animal can be directly genetically modified through the insertion of genes into the egg of the animal. This technique is used, for example, to increase the amount of casein in dairy cattle to increase milk protein and also to insert a growth hormone gene similar to insulin into swine to reduce fat and increase feed efficiency.

In addition, there are proposals to genetically modify animals to produce medicines or chemicals. For example, some have proposed to genetically engineer an animal to make milk that contains insulin. Companies are also performing research on using the mammary gland of sheep, goats and cows to produce proteins for drugs for humans. Moreover, genetically modified animals could provide organs and tissues for use in human transplant surgery. Organs from animals can be genetically modified so that they carry copies of the human genes that code for proteins inhibiting the immune response to foreign tissue. This might reduce the risk of rejection by the human immune system.

Since the 1980s, there has been a burst of biotechnology activity in research and development related to various fish species, in particular those used in aquaculture production (Pew Initiative, 2003). Traits that are being tested in fish species such as carp, trout, salmon and channel catfish include growth rates that are three to eleven times faster with more efficient feed utilisation, increased tolerance to cold water and improved disease resistance. Accelerated growth rates mean that fish reach marketable size sooner, thereby reducing overhead costs for fish farmers. In addition, researchers use the human interferon gene to improve disease resistance in carp, which could reduce the amount of antibiotics needed to keep fish healthy and reduce the costs incurred from losses due to disease. The first (and to date only) genetically engineered fish to be sold commercially is the fluorescent Glofish®, a zebra fish modified to glow red, which came onto the US market in 2004.

Animal cloning builds on pre-existing reproductive technologies in the hopes of creating animals with better characteristics, often through the cloning of GM animals. In 1997, a group of Scottish researchers announced the birth of Dolly the sheep – the world’s first mammal cloned from an adult cell. Dolly has the same genes as the ewe from which an udder cell was taken and fused with an empty egg (whose nucleus was removed). The egg, with its new genome, was stimulated to begin developing into an embryo and was implanted into a surrogate sheep where it grew normally, resulting in the birth of Dolly.

GM insects are a new area of study in which the majority of the research is being carried out by government scientists, philanthropic organisations and publicly funded research institutions (Pew Initiative, 2004; Pew Initiative, 2005a). The focus of the research is currently on engineering insects to prevent them from spreading diseases such as malaria or to reduce populations of insect pests that destroy agricultural crops. One of the most advanced applications includes research to insert a marker gene into a male fruitfly that has been made sterile through conventional processes. The sterile fruitfly will then be released into the wild with the aim of decreasing fruitfly populations and thereby crop damage. The insertion of a marker gene would enable scientists and regulators to assess the extent to which the fruitflies have served their purpose of decreasing populations. Experts suggest that this relatively low-risk genetic modification could be the first to be discussed with the public and regulators regarding potential release, which is not estimated to happen until 2015 at the earliest.

 

 

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