# Genes, Technology and Policy/Applications in Agriculture
## What are the applications of modern biotechnology in agriculture?

There are many applications of biotechnology in agriculture.
Improved yield from crops. Using the techniques of modern biotechnology, one or two genes may be transferred to a highly developed crop variety to impart a new character that would increase its yield. However, while increase in crop yield is the most obvious application of modern biotechnology in agriculture, it is also the most difficult one. Current genetic engineering techniques work best for effects that are controlled by a single gene. Many of the genetic characteristics associated with yield (e.g., enhanced growth) are controlled by a large number of genes, each of which has a minimal effect on the overall yield. There is, therefore, much scientific work to be done in this area.
Reduced vulnerability of crops to environmental stresses. Crops containing genes that will enable them to withstand biotic and abiotic stresses may be developed. For example, drought and excessively salty soil are the two most important limiting factors in crop productivity. Biotechnologists are studying plants that can cope with these extreme conditions in the hope of finding the genes that enable them to do so and eventually transferring these genes to the more desirable crops. One of the latest developments is the identification of a plant gene, At-DBF2, from thale cress, a tiny weed that is often used for plant research because it is very easy to grow and its genetic code is well mapped out. When this gene was inserted into tomato and tobacco cells, the cells were able to withstand environmental stresses like salt, drought, cold and heat, far more than ordinary cells. If these preliminary results prove successful in larger trials, then At-DBF2 genes can help in engineering crops that can better withstand harsh environments.
Researchers have also created transgenic rice plants that are resistant to rice yellow mottle virus (RYMV). In Africa, this virus destroys majority of the rice crops and makes the surviving plants more susceptible to fungal infections.
Increased nutritional qualities of food crops. Proteins in foods may be modified to increase their nutritional qualities. Proteins in legumes and cereals may be transformed to provide the amino acids needed by human beings for a balanced diet. A good example is the work of Professors Ingo Potrykus and Peter Beyer on the so-called Goldenrice™(discussed below).
Improved taste, texture or appearance of food.Modern biotechnology can be used to slow down the process of spoilage so that fruit can ripen longer on the plant and then be transported to the consumer with a still reasonable shelf life. This improves the taste, texture and appearance of the fruit. More importantly, it could expand the market for farmers in developing countries due to the reduction in spoilage.
The first genetically modified food product was a tomato which was transformed to delay its ripening. Researchers in Indonesia, Malaysia, Thailand, Philippines and Vietnam are currently working on delayed-ripening papaya in collaboration with the University of Nottingham and Zeneca.
Reduced dependence on fertilizers, pesticides and other agrochemicals. Most of the current commercial applications of modern biotechnology in agriculture are on reducing the dependence of farmers on agrochemicals. For example, Bacillus thuringiensis (Bt) is a soil bacterium that produces a protein with insecticidal qualities. Traditionally, a fermentation process has been used to produce an insecticidal spray from these bacteria. In this form, the Bt toxin occurs as an inactive protoxin, which requires digestion by an insect to be effective. There are several Bt toxins and each one is specific to certain target insects. Crop plants have now been engineered to contain and express the genes for Bt toxin, which they produce in its active form. When a susceptible insect ingests the transgenic crop cultivar expressing the Bt protein, it stops feeding and soon thereafter dies as a result of the Bt toxin binding to its gut wall. Bt corn is now commercially available in a number of countries to control corn borer (a lepidopteran insect), which is otherwise controlled by spraying (a more difficult process).
Crops have also been genetically engineered to acquire tolerance to broad-spectrum herbicide. The lack of cost-effective herbicides with broad-spectrum activity and no crop injury was a consistent limitation in crop weed management. Multiple applications of numerous herbicides were routinely used to control a wide range of weed species detrimental to agronomic crops. Weed management tended to rely on preemergence—that is, herbicide applications were sprayed in response to expected weed infestations rather than in response to actual weeds present. Mechanical cultivation and hand weeding were often necessary to control weeds not controlled by herbicide applications. The introduction of herbicide tolerant crops has the potential of reducing the number of herbicide active ingredients used for weed management, reducing the number of herbicide applications made during a season, and increasing yield due to improved weed management and less crop injury. Transgenic crops that express tolerance to glyphosphate, glufosinate and bromoxynil have been developed. These herbicides can now be sprayed on transgenic crops without inflicting damage on the crops while killing nearby weeds.
From 1996 to 2001, herbicide tolerance was the most dominant trait introduced to commercially available transgenic crops, followed by insect resistance. In 2001, herbicide tolerance deployed in soybean, corn and cotton accounted for 77% of the 62.6 million hectares planted to transgenic crops; Bt crops accounted for 15%; and stacked genes for herbicide tolerance and insect resistance used in both cotton and corn accounted for 8%.
Production of novel substances in crop plants.Modern biotechnology is increasingly being applied for novel uses other than food. For example, oilseed is at present used mainly for margarine and other food oils, but it can be modified to produce fatty acids for detergents, substitute fuels and petrochemicals. Banana trees and tomato plants have also been genetically engineered to produce vaccines in their fruit. If future clinical trials prove successful, the advantages of edible vaccines would be enormous, especially for developing countries. The transgenic plants may be grown locally and cheaply. Homegrown vaccines would also avoid logistical and economic problems posed by having to transport traditional preparations over long distances and keeping them cold while in transit. And since they are edible, they will not need syringes, which are not only an additional expense in the traditional vaccine preparations but also a source of infections if contaminated.
Figure 7 provides a panoramic view of other potential applications of modern biotechnology in agriculture.
Figure 7.

## There have been reports about modifying rice to address problems of deficiency in Vitamin A. Is this true, and will the technology be available to developing countries?

Yes, there are efforts to improve the nutritional quality of rice. This staple food for two billion people is usually milled to remove the outer layers to prevent their high oil content from causing spoilage. The remaining grains are low in B-carotene, the chemical precursor of vitamin A. Some 400 million people worldwide suffer from vitamin A deficiency while over 3.7 billion people are iron-deficient. Vitamin A deficiency causes five million deaths annually, and blindness in a further 500,000 people, while iron deficiency causes anemia and birth defects.
Golden Rice™is a transgenic crop created by Dr. Ingo Potrykus and his colleagues to improve the nutritional quality of rice by increasing the quantities of beta carotene (the precursor of vitamin A) and improving the crop’s iron content. Several genes have been inserted into the rice genome, including a daffodil gene, allowing the endosperm (the part that remains after milling and polishing) to produce B-carotene. Additionally, a phytase gene (which produces an enzyme to release chemically-bound iron), a gene to increase organic iron, and a gene to aid iron absorption in the digestive tract have been added. The presence of beta carotene in the endosperm of the transgenic rice gives it a golden color. Hence, the name “golden rice”.
The research, which was funded by the Rockefeller Foundation, the Swiss government and the European Union, hopes to provide a cheap form of vitamin supplementation. If it is later proven to be viable and safe, Golden Rice will be distributed in developing countries, with no patents blocking access to it. The introduction of vitamin A-producing beta carotene into the rice gene has the potential of addressing the vitamin A problem, especially among those who are too poor to diversify their diets with green vegetables.

## How is modern biotechnology in agriculture different from traditional plant breeding techniques? Is modern biotechnology simply a more advanced stage in the biotechnology development continuum?

Yes and no. Yes, because both traditional and modern biotechnology involve the transfer of genes from one organism to another. Traditional breeding techniques typically involve the repeated mixing of thousands of genes over several years and many generations of plants to achieve a desired trait. Modern biotechnology accelerates this lengthy process by allowing scientists to insert selected genes directly into a plant. This makes modern biotechnology less of an iterative process compared to traditional plant breeding techniques. In this sense, modern biotechnology is simply an extension of traditional breeding.
No, because unlike traditional breeding techniques, modern biotechnology can move genes across species, even family, boundaries to produce novel organisms that do not normally occur in nature. To cite a simplistic example, a brown cow that mates with a yellow cow may produce a calf of a completely new color, but reproductive mechanisms limit the number of new combinations. Cows must breed with other cows or their very near relatives. A farmer cannot breed for a purple cow using traditional sexual reproduction techniques because the necessary purple genes are not available in cows or their near relatives. In contrast, the biological barrier is not as steep, at least in theory, to a genetic engineer. If purple genes are available in another species, say in an iris plant, those genes could be mixed with the genes of the cow to produce purple cows.

## How are genes inserted into plants using modern biotechnology?

There are currently two commonly used methods for introducing genes into plants genomes:
1. Using a plasmid vector. As previously discussed, a vector, like the plasmids of Agrobacterium tumefaciens, may be used to introduce the gene or genes of interest into the plant DNA. The resulting cells are then screened to identify those that have successfully expressed the new trait. The modified seeds are sown in the field and grown like any other crop.
2. Particle bombardment techniques. The DNA to be introduced into plant cells is coated onto tiny particles, which are then physically shot into the plant cells. Some of the DNA comes off and are incorporated into the DNA of the target plant.

## Are transgenic crops now commercially available?

Yes, genetically modified crops are now available in the market. If you eat corn or soya products, chances are you are consuming genetically modified products. In the United States, it is estimated that 70-85% of all processed/packaged foods contain one or more ingredients that are derived from transgenic crops.
James (2002) estimated the global area planted to transgenic crops in 2002 at 58.7 million hectares. More than one-quarter of this area, or 13.5 million hectares, is in six developing countries, namely, China, India, Indonesia, Argentina, South Africa, and Mexico. India, the largest cotton growing country in the world, commercialized Bt cotton for the first time during the year. However, four countries continue to account for 99% of the global transgenic crop area. The USA grew 66% of the global total, followed by Argentina with 23%, Canada with 6%, and China with 4%. China had the highest year-on-year percentage growth, with a 40% increase in its Bt cotton area.
The adoption rate for transgenic crops is the highest in the history of agriculture. From 1996 to 2000, 15 countries contributed to a more than 25-fold increase in the global area of transgenic crops, from 1.7 million hectares in 1996 to 44.2 million hectares in 2000.

## Which transgenic crops dominate in terms of acreage?

In 2001, the principal transgenic crops were soybean, with 62% of the global area, followed by corn at 21%, cotton at 12%, and canola at 5%. More than three-quarters of the transgenic crops were modified for herbicide tolerance. The balance was mostly for pest resistance, with a few areas planted to potato and papaya with inserted genes for delayed ripening and virus-resistance.

## Is genetic engineering in agriculture harmful to the environment?

Most of the concerns revolve around the effect of biotechnology products on the environment and on human health.
Like all new technologies, genetic engineering, if not properly studied and regulated, can adversely impact on the environment. However, we need to review the impact on a case-by-case basis. Biotechnology by itself is not good or bad. As with all technologies, it is how people use it that can be good or bad, risky or beneficial. Each biotechnology product must be evaluated in terms of whether it is useful, beneficial and safe. To date, there is no scientific proof that the use of modern biotechnology has an adverse effect on the environment and on human health.
The major issues that have been raised so far against the environmental impact of genetically engineered agricultural products and the corresponding scientific consensus are summarized below:
1. Increased weediness. One concern is that altered plants may have increased fitness to survive their environments and might grow unaided by human beings in places where they could have unwanted effects. In unmanaged environments, they could displace natural flora and upset entire ecosystems. However, in a 10-year study to answer the question of whether transgenes conferring herbicide tolerance or insect resistance on crop plants also confer weediness or invasiveness, it was found that genetically modified crops (those that are commercially available) have no more tendency to become weeds than their conventionally bred counterparts. Apparently, more genes are needed to convert a plant into a weed. Another study also showed that biological invasions have extensive time lags that range from 30-150 years and require the chance concordance of favorable conditions before taking off. The question, however, is whether transgenes would hasten this process. This is why potential invasiveness of GM plants is evaluated before any decision to release them into the environment is made.
2. Unintended gene flow. There is also the concern that if relatives of the altered crops are growing near a field with their conventional counterpart, the new gene could move by means of pollen transfer into the latter. There is merit in this concern. This is why studies have to be done on a case-by-case basis to determine the potential environmental risks due to unintended gene flow. The European Science Foundation and European Environment Agency (2002) recently released their report on the significance of pollen-mediated gene flow from six major crop types that have been genetically engineered and are close to commercial release in the European Union, namely, oilseed rape, sugar beet, potatoes, maize, wheat and barley. They found, among others, that oilseed rape is high-risk for crop-to-crop gene flow and gene flow from crop to wild relatives. Potatoes, wheat, and barley are low-risk crops. Maize and sugar beet are both medium- to high-risk for crop-to-crop gene flow, with the latter having the same level of risk for gene flow from crop to wild relatives. There are no known wild relatives of maize in Europe with which it can hybridize.
On the other hand, there is much research on developing alternative measures to mitigate unintended gene flow. At present, seed producers of conventional crops can devise mechanisms to isolate their crop lands from related plants in order to maintain the purity of their lines. In addition, several biotechnology measures to prevent horizontal gene flow, such as apomixis, chloroplast transformation, chromosome-specific cytogenetic system, and transgenetic mitigation, have been suggested. The most controversial is the Technological Protection System (TPS) developed by the U.S. Department of Agriculture and Delta & Pine. The technique, commonly called GURT (for Genetic Use Restriction Technology), involves a system of three genes that interact to control the fertility of seeds by the seed producer. The objection to TPS has to do with the possibility of pollen dispersal to adjacent fields of the same crop, inadvertently causing the latter to produce sterile seeds. This would also have a severe impact on the common practice of seed saving among small farmers in developing countries.
3. Change in herbicide use patterns. It has been pointed out that widespread use of herbicide-tolerant crops could lead to the rapid evolution of resistance to herbicides in weeds, either as a result of increased exposure to the herbicide or as a result of the transfer of the herbicide trait to weedy relatives of the crops. However, to date there is no evidence that this phenomenon is taking place.
4. Squandering of valuable pest susceptibility genes. Many insects contain genes that render them susceptible to pesticides. Often these susceptibility genes predominate in natural populations of insects. These genes are a valuable natural resource because they allow pesticides to remain as effective pest-control tools. The more benign the pesticide, the more valuable the genes that make pests susceptible to it. It is feared that crops that have been altered to contain the pest-resistance Bt gene can adversely affect the continued susceptibility of pests to the Bt toxin. The continuous exposure of pests to the Bt toxin in altered crops selects for the rare resistance genes in the pest population and in time will render the Bt pesticide useless, unless specific measures are instituted to avoid the development of such a resistance. It should be noted, however, that there is really no such thing as permanent resistance to pests and diseases and that insect resistance happens under the current practice of using pesticides or even in nature.

## A few years ago, there was a controversy around the effect of genetically modified corn on Monarch butterflies. What was that controversy all about and did it have scientific basis?

Monarch butterfly larvae feed exclusively on the leaves of milkweed plants, which are commonly found in cornfields in the U.S. Pollen from nearby corn can become distributed on the leaves of these plants, and can therefore be eaten by the larvae. In 1999, two studies showed that Monarch butterfly larvae and larvae from related species that were fed leaves dusted with Bt-corn pollen had lower survival rates, compared to those fed leaves dusted with non-Bt corn pollen. These studies were used to suggest that Bt corn was responsible for the recently observed decline in the Monarch butterfly population.
However, subsequent investigations revealed that while a large percentage of Monarch butterfly larvae may feed on milkweed found in the corn belt region of the U.S., there is no overlap between their breeding time and the time of pollen shed through most of this region. Other studies have shown that corn pollen settling on an area decreases rapidly with distance. This and the toxicity studies showing low toxicity of many major Bt-corn strains indicate that pollen densities that could represent significant exposure to feeding larvae are found only within five meters of cornfields, and then rarely. The current scientific consensus is that the adverse impact of Bt-corn pollen observed in the laboratory does not occur in the fields. Hence, Monarch butterflies are safe from Bt corn.

## Are GM foods safe to eat?

At present, there are no studies to indicate that any of the commercially available GM foods are any less safe than their non-modified counterparts. This, of course, does not mean that all products of biotechnology are safe. Hence, the need for regulations. In fact, GM food products are subjected to more tests than their conventionally-bred counterparts.
The concerns raised about the safety of genetically engineered food products fall into the following categories:
1. New allergens in the food supply
There is a concern that transgenic crops could introduce new allergens into foods. However, it is important to keep in mind that eating conventional food is also not risk-free; allergies occur with many new and even known conventional foods. For example, the kiwi fruit was introduced into the U.S. and the European market in the 1960s with no known human allergies; today, there are people allergic to this fruit. In February 2002, the Royal Society issued a policy report titled Genetically Modified Plants for Food Use and Human Health—An Update. The report concluded that there is currently no evidence that GM foods cause allergic reactions and “the allergenic risks posed by GM plants are in principle no greater than those posed by conventionally derived crops or by plants introduced from other areas of the world.”
2. Antibiotic resistance
Modern biotechnology often uses genes for antibiotic resistance as “selectable markers”. Early in the genetic engineering process, these markers help select cells that have taken up the foreign genes. Although they have no further use, the genes continue to be expressed in plant tissues. Critics of modern biotechnology argue that the presence of antibiotic-resistance genes could have two harmful effects. First, eating food containing these genes could reduce the effectiveness of antibiotics to fight disease when these antibiotics are taken with meals. Antibiotic resistance genes produce enzymes that can degrade antibiotics. If a tomato with an antibiotic-resistance gene is eaten at the same time as an antibiotic, it could destroy the antibiotic in the stomach. Second, the resistance genes could be transferred to human or animal pathogens, making them impervious to antibiotics. If transfer were to occur, it could aggravate the already serious health problem of antibiotic-resistant disease organisms.
However, unmediated transfers of genetic material from plants to bacteria are highly unlikely. Moreover, several strategies have been developed to avoid the inclusion of antibiotic resistance genes in the commercial transgenic variety.
3. Production of new toxins
Many organisms have the ability to produce toxic substances. For plants, such substances help to defend stationary organisms from many predators in their environment. But there is concern that the addition of new genetic material through genetic engineering could trigger the production of toxic substances within plants. This could happen, for example, if the on/off signals associated with the introduced gene were located in the genome in places where they could turn on the previously inactive genes.
Human beings typically eat several grams of DNA in their diet each day. Hence, the transgene in a genetically engineered plant is not a new type of material to our digestive systems. It is also present in extremely small amounts. In transgenic corn, for example, the transgenes represent about 0.00018 of the total DNA. Decades of research indicate that dietary DNA has no direct toxicity. In fact, exogenous nucleotides have been shown to play important beneficial roles in gut function and the immune system. Likewise, there is no compelling evidence showing the incorporation and expression of plant-derived DNA, whether a transgene or not, into the genomes of a consuming organism.
Defense processes have evolved, including extensive hydrolytic breakdown of the DNA during digestion, excision of integrated foreign DNA from the host genome, and silencing of foreign gene expression by targeted DNA methylation, that prevent the incorporation or expression of foreign DNA. Thus, there is a minimal possibility of adverse effects arising from the presence of foreign DNA by either direct toxicity or gene transfer.
4. Effect on nutrients
Concerns have been raised regarding the possible adverse effect of genetic engineering technology on the nutritional content of food. This is a legitimate concern for regulators. In the U.S., for example, the Food and Drug Administration ensures that the nutritional composition of GM foods is substantially equivalent to that of their conventional counterparts. Studies are performed to determine whether nutrients, vitamins and minerals in the modified food occur at the same levels as in the conventionally-bred food sources. For example, seeds and toasted soybean meal from Roundup Ready™soybeans have been compared to conventional soybeans in terms of protein, oil, fiber, ash, carbohydrates, moisture content, amino acid and fatty acid composition. The results showed that the composition of transgenic lines is equivalent to that of conventional soybean cultivars, except for the trypsin inhibitors in non-toasted soybean meal, which is not consumed. In addition, the equivalence of the feeding value of the transgenic grains was demonstrated in rats, chickens, catfish and dairy cattle.
5. Concentration of toxic metals
Some of the new genes being added to crops can remove heavy metals like mercury from the soil and concentrate them in plant tissue. The purpose of creating such crops is to make possible the use of municipal sludge as fertilizer. Sludge contains useful plant nutrients but often cannot be used as fertilizer because it is contaminated with toxic heavy metals. The idea is to engineer plants to remove and sequester those metals in inedible parts of plants. In a tomato, for example, the metals would be sequestered in the roots. Turning on the genes in only some parts of the plant requires the use of genetic on/off switches that turn on only in specific tissues, like roots. Such products could pose the risk of contaminating foods with high levels of toxic metals if the on/off switches are not completely turned off in edible tissues. There are also environmental risks associated with the handling and disposal of the metal-contaminated parts of plants after harvesting. Regulations have to address the peculiar functions of GMOs being used as bioremediation agents.

## A previous study of the adverse effect of GM potatoes on rats is cited by critics of biotechnology as evidence that GM products are unsafe. What happened to that study?

The study was found to be inconclusive.
Dr. Arpad Putztai, a senior scientist at the Rowett Institute in Aberdeen, Scotland, came to international attention when he announced to the media that eating genetically modified potatoes depressed rat immune systems and caused changes in their intestinal tract. Dr. Putztai and his co-workers compared rats fed genetically modified potatoes with rats fed non-modified potatoes, with and without added GNA. The genetically modified potatoes appeared to cause changes in the rats’ immune response and the structure of the intestinal lining.
But there was a flaw in the experiment. While its design was apparently correct for this type of feeding study, rats do not like to eat raw potato. As a result, a standard 110-day trial had to be abandoned after only 67 days because the rats were starving. Starvation affects gut histology, and even the lining of the guts of rats eating unmodified potatoes was shown to be abnormal. The presence of other potato toxins could also have had a confounding effect on cells in the intestine, especially since the potato lines were not substantially equivalent

## Does the possible transfer of antibiotic resistance marker genes from ingested GM food to gut microbes pose a significant hazard to human beings?

Organisms that contain DNA encoding for antibiotic resistance proteins are common and are becoming more prevalent in the environment. However, there is no documented evidence that the antibiotic resistance markers in GM foods contribute to antibiotic resistance in gut bacteria. Should there be such a contribution, it is expected to be extremely small for several reasons, including the efficient destruction of the resistance gene in the human gut and the extremely low intrinsic rate of plant-microbe gene transfer.
Furthermore, resistance genes occur quite widely already and the antibiotics involved are not widely used in medical practice. Finally, the technology is now available to omit the use of such selections devices and their use is therefore likely to diminish.

## What is the “principle of substantial equivalence”?

The term “substantial equivalence” was first mentioned in 1993 in connection with food safety in a report of the OECD Group of National Experts on Safety in Biotechnology. The members of the group agreed that the most practical approach to determining the safety of foods derived by modern biotechnology is to consider whether they represent a substantial equivalent to analogous traditional products. The term substantial equivalence and the underlying approach were borrowed from the U.S. Food and Drug Administration’s definition of a class of new medical devices that do not differ materially from their predecessors and thus do not raise new regulatory concerns.
According to the OECD definition, the concept of substantial equivalence is based on the idea that existing products used as foods or food sources can serve as a basis for comparison when assessing the safety and the nutritional value of a food or food ingredient that is new or that has been modified by modern biotechnological methods. If a novel food or novel food component is found to be substantially equivalent to an existing food or food component, it can be treated in the same manner with respect to safety. No additional safety concern would be expected. If a novel food or novel food ingredient is not found to be substantially equivalent to its conventional counterpart, this does not imply that it is unsafe. It must simply be evaluated on the basis of its unique composition and properties.

## What is the “precautionary principle”?

The “precautionary principle” traces its origins to Principle 15 of the Rio Declaration on Environment and Development, which provides that:
    In order to protect the environment, the precautionary approach shall be widely applied by the States according to their capabilities. Where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation.
The use of the precautionary principle is to be based to the fullest extent possible on scientific evidence of a given problem. However, it is not always possible to move towards a decision on a purely scientific assessment; any assessment must also involve economic, social and ethical aspects. The precautionary principle is thus more of a political norm than a clearly defined concept.
Critics of the precautionary principle have argued that it is poorly defined, not sufficiently grounded in science, stifles development of technology, and hinders trade. It is claimed that it is not a valid principle for evaluating scientific evidence as it distorts reality and leads to the acceptance of false beliefs. Opponents are also concerned that the precautionary principle’s focus on hypothetical risks will distract consumers and policy makers from the policies needed to address known food-borne threats to human health.
The precautionary principle has been invoked to justify a prohibition of GM crops. The justification for a ban allegedly considers the potential public health and environmental benefits of the banned GM crop. However, it ignores the probable public health and environmental benefits that would necessarily be foregone as a result of the ban. A comprehensive application of the precautionary principle indicates that a GM crop ban, contrary to the claims of its advocates, would increase overall risks to public health and to the environment, especially in developing countries. Thus, it would be more prudent to study, develop, and possibly commercialize GM crops than to ban such crops, provided reasonable caution is exercised through the regulatory agencies.

## Should it wish to do so, how should a government regulate the use of modern biotechnology?

The purpose of a biosafety (short for “biological safety”) system is to control the risks associated with the products of modern biotechnology. An integrated national biosafety system has the following elements:
1. National policy, strategies and research agenda regarding biosafety. The development of a national biosafety system should begin with the elaboration of a national biosafety policy consistent with a country’s other policy objectives on food, agriculture, the environment and sustainable development. This policy will serve as the basis for the crafting of specific legislation and/or regulations on biosafety. It should articulate a framework where competing goals, such as economic, regional development and environmental protection, may be integrated and communicated as a single national vision.
2. National inventory and evaluation. This is a means to identify and characterize the available resources and regulatory infrastructure in a country, assess their adequacy for supporting a biosystem, and identify gaps where capacities need to be strengthened. The inventory should include the following factors:
* existing regulatory structures and legislation pertaining to the import and export of agricultural commodities, environmental protection, animal and human health safety, and biotechnology
* existing mechanisms for the development of public policy, legislation, and regulations
* existing human, financial and scientific infrastructure
* the current status of biotechnology research and development, including programs for the safe use and handling of GMOs
* existing mechanisms for regional cooperation and regulatory harmonization
* existing capacity building programs
* the role of civil society in policy and regulatory development processes
* administrative and enforcement capacity
3. Knowledge, skills and capacity base to develop and implement a biosafety system. A strong base of scientific knowledge to support the regulatory system and the development of competencies in product evaluation is critical to any biosafety system. A limited knowledge and skills base will tend to produce regulations that are highly protective, at the expense of innovation.
Some countries have implemented a system of expert advisory committees, while others have relied primarily on scientists and professionals working within government agencies. The advantage of independent advisory committees is that they generally have more transparent accountability frameworks because the expertise and academic credentials of their membership are usually published. However, they may suffer from the part-time volunteer nature of their membership. A combination of these two approaches—expert advisory committees and government scientists and professionals—may be the best arrangement. Product evaluations performed by competent scientists within a regulatory agency could be supplemented by the results of issue-specific expert panel consultations.
    Box 3. Risk Assessment
* What is risk assessment?
Risk assessment is a method by which science can be used to address environmental and human health safety concerns. It is broadly defined as the use of scientific data to rank or measure hazards, assess exposure and characterize risks involved in a food-related activity or product. However, risk assessments do not specifically determine whether a product is “safe” or “unsafe”. The use of risk assessment in the development of regulations is related to the expected impact of a particular environmental or food safety problem, the expected impact of protective mitigation measures, and the levels of urgency and controversy surrounding an issue.
* What are the principles of risk assessment as applied to GMOs?
There are four basic principles that have found international acceptance. These are embodied in Annex III of the Cartagena Protocol:
1. Risk assessment should be carried out in a scientifically sound and transparent manner, and can take into account expert advice of, and guidelines developed by, relevant international organizations.
2. Lack of scientific knowledge or scientific consensus should not necessarily be interpreted as indicating a particular level of risk, an absence of risk, or an acceptable risk.
3. Risks associated with living modified organisms or products thereof, namely, processed materials that are of living modified organism origin, containing detectable novel combinations of replicable genetic material obtained through the use of modern biotechnology, should be considered in the context of the risks posed by the non-modified recipients or parental organisms in the likely potential receiving environment.
4. Risk assessment should be carried out on a case-by-case basis. The required information may vary in nature and level of detail from case to case, depending on the living modified organism concerned, its intended use and the likely potential receiving environment.
* What are the limitations of scientific risk assessment?
In risk assessment analysis, the use of science is not as clear-cut and simple as it may appear initially. First, since scientific knowledge constantly changes and evolves, the best available science about food or environmental issues may be different from one year to the next.
Another complicating factor in the application of science to risk assessment analysis is the disagreement among scientists about conclusions from key influential studies. Ideally, scientists conduct research in a manner that produces precise and accurate results so that study conclusions are authoritative and nonbiased. However, it is not unusual for scientists to disagree about an experiment’s design and conclusions, especially if the results alter the conventional knowledge about a subject. These disagreements may require years of debate and further experimentation in other laboratories before results are accepted by most scientists. Regulations based on professionally disputed scientific studies may not be scientifically defensible once the controversy is resolved through additional data gathering and analysis.
* Given the above limitations, should one continue to use scientific risk assessment in evaluating biotechnology products?
Yes, there is no other internationally accepted standard by which one can effectively assess the risks, if any, posed by GM products. One should, however, be cognizant of the above limitations in arriving at a decision involving GMOs.
4. Development of regulations. A country may adopt either voluntary guidelines or mandatory regulations. Voluntary guidelines are more quickly put in place and are more flexible for the adoption of revisions incorporating new information requirements. However, the public may not be as confident with voluntary guidelines as they would be with mandatory regulations. Thus, there may be value in adopting mandatory regulations.
If a country elects to develop mandatory regulations, it can do so in one of two ways: (1) it can develop a new act and regulations to specifically address GMOs; or (2) it can regulate GMOs using existing legal instruments such as acts, regulations, and presidential decrees. The former has the advantage of establishing a system that specifically addresses the product or process to be regulated, of being crafted to allow flexibility in the face of new technical advances, and of being perceived by the public as a positive response to addressing the concerns about safety of GMOs. However, it could take long to develop such a new act or regulation, especially with the political controversy that GMOs have generated. Also, this could result in GMOs being regulated in perpetuity even if the scientific basis for the separate regulation has long been eroded.
If a mandatory system is adopted, the policy maker should also decide on whether the system should take any of the following forms:
* ex ante regulation in the form of required permits, licenses, regulations, and product approvals before any GM product is used or released, whether for experimental or commercial purposes;
* strict ex post facto liabilities in the form of damage payments by the biotechnology research organization or business entities; or
* a negligence rule, which is a combination of the ex ante regulation and ex post facto liabilities.
The biosafety policy developed in most countries emphasizes the ex ante regulatory approach. This approach has the major benefit of providing information to both the producer and consumer of biotechnology products. If a biotechnology organization produces new products according to the regulations, it is less likely to be fined ex post facto. Thus, regulation and product standards reduce risk and thereby allow the market to work more smoothly as the participants are better informed about the rules of the game.
Ultimately, the development of biosafety policy will depend on several factors including the nature of risks, the goal of public policy, the institutional and judicial framework, and the involvement of the private sector in biotechnology research.
Regardless of the type of regulatory framework chosen, care must be taken not to overregulate. An unreasonably stringent regulatory system can prevent beneficial products from being made available to the public.
5. Implementation of regulations. The final step of putting the system into operation requires the following elements:
* The regulations or guidelines clearly define the structure of the biosafety system.
* People are knowledgeable and well trained.
* The review process is based on up-to-date scientific information.
* Feedback mechanisms are used to incorporate new information and revise the system as needed.

## What international agreements are relevant to modern biotechnology?

Issues related to modern biotechnology have been raised in a number of international fora, including the following:
* Convention on Biological Diversity (CBD)
* Food and Agriculture Organization (FAO)
* Organization for Economic Cooperation and Development (OECD)
* World Trade Organization (WTO)
* World Health Organization (WHO)
* World Intellectual Property Organization (WIPO)
* Asia Pacific Economic Cooperation (APEC)
* Office of International Epizootics (OIE)
* International Plant Protection Convention (IPPC)
* Codex Alimentarius Commission (CAC)
* World Bank
There are also a number of international agreements that relate to modern biotechnology. The most important are the:
* Cartagena Protocol on Biosafety to the United Nations Convention on Biological Diversity
* Agreement on Technical Barriers to Trade
* Agreement on the Application of Sanitary and Phytosanitary Measures
* WTO Agreement on Trade-Related Aspects of Intellectual Property Rights

## What is the Cartagena Protocol on Biosafety?

The Cartagena Protocol on Biosafety to the Convention on Biological Diversity is the first international legally binding tool regarding biosafety in biotechnology. It seeks to contribute to ensuring that there is an adequate level of protection in the safe transfer, handling and use of GMOs resulting from modern biotechnology, especially those that may have adverse effects on the conservation and sustainable use of biological diversity. It also takes into account risks to human health, and specifically focuses on transboundary movements.
The Protocol was adopted in Montreal on January 29, 2000, but will take effect only after at least 50 States have ratified it. In summary, the Protocol:
* Establishes an Advance Informed Agreement procedure for imports of LMOs intended for release into the environment;
* Establishes a simplified procedure for notification and information exchange for LMOs intended for food, feed or for processing, such as agricultural commodities;
* Establishes regimes for assessing and managing risks to biodiversity;
* Details information and documentation requirements; and
* Includes provision for capacity-building and financial resources.
    Box 4. The Advanced Informed Agreement Procedure
A Party1 exporting a living modified organism (LMO) to another Party for intentional introduction into the latter’s environment is required to comply with the advance informed agreement procedure laid down by the Cartagena Protocol. The Advance Informed Agreement, which is the heart of the Cartagena Protocol, is as follows:
1. Prior to the intentional transboundary movement of the LMO, the Party of export should notifies, or requires the exporter2 in its jurisdiction to ensure notification, in writing, to the competent national authority3 of the Party of import. The notification should contain the following minimum information4:
a. Name, address and contact details of the exporter;
b. Name, address and contact details of the importer5;
c. Name and identity of the LMO, as well as the domestic classification, if any, of the biosafety level of the LMO in the State of export;
d. Intended date or dates of the transboundary movement, if known;
e. Taxonomic status, common name, point of collection or acquisition, and characteristics of recipient organism or parental organisms related to biosafety;
f. Centers of origin and centers of genetic diversity, if known, of the recipient organism and/or the parental organisms and a description of the habitats where the organisms may persist of proliferate;
g. Taxonomic status, common name, point of collection or acquisition, and characteristics of the donor organism or organisms related to biosafety;
h. Description of the nucleic acid or the modification introduce, the technique used, and the resulting characteristics of the LMO;
i. Intended use of the LMO or products thereof, namely, processed materials that are of LMO origin, containing detectable novel combinations of replicable genetic material obtained through the use of modern biotechnology;
j. Quantity or volume of the LMO to be transferred;
k. A previous and existing risk assessment consistent with the risk assessment principles and methodology set forth on the Protocol;
l. Suggested methods for the safe handling, storage, transport and use, including packaging, labeling, documentation, disposal and contingency procedures, where appropriate;
m. Regulatory status of the LMO within the State of export (for example, whether it is prohibited in the State of export, whether there are other restrictions, or whether it has been approved for general release) and, if the LMO is banned in the State of export, the reason or reasons for the ban;
n. Result and purpose of any notification by the exporter to other States regarding the LMO to be transferred; and
o. A declaration that the above-mentioned information is factually correct.
2. Within ninety days from receipt of the notification, the Party of import acknowledges such receipt in writing. The acknowledgment should state the following:
a. the date of receipt of the notification;
b. whether the notification, prima facie, contained the required minimum information listed above; and
c. whether the notifier should proceed according to the domestic regulatory framework of the Party of import (which must be consistent with the Cartagena Protocol) or according to the Decision Procedure laid down by the Cartagena Protocol itself.
The failure by the Party of import to acknowledge receipt of a notification within the 90- day period does not imply consent to the transboundary movement.
3. If the Party of import requires the notifier to comply with the Decision Procedure of the Protocol, then:
a. within the same period required to acknowledge the notification, the Party of import informs the notifier, in writing, whether the transboundary transfer may proceed either: (a) only after the Party of import has given its written consent; or (b) after no less than ninety days without a subsequent written consent; and
b. within two hundred seventy days from receipt of notification, the Party of import should communicate, in writing, to the notifier and to the Biosafety Clearing-House6 of its decision:
    i. approving the import, with or without conditions, including how the decision will apply to subsequent imports of the same LMO;
    ii. prohibiting the import; or
    iii. to request additional information in accordance with its domestic regulatory framework or Annex of the Protocol7
    iv. to extend the 270-day period by a definite period of time.
Failure by the Party of import to inform the notifier of its decision within the 270-day period does not imply consent to the transboundary movement.
The Advance Informed Agreement applies only for the first intentional introduction of the LMO into the environment of the Party of import, as is the case when, for instance, the LMO is being imported for use in field trials. It does not apply in instances where the LMO is:
* in transit;
* intended for use in a contained facility8 (e.g., laboratory and greenhouse); or
* intended or for food, feed, or for processing into food or feed,9 which is covered by the separate procedure outline in Box 5.
Notes
1 A State or a regional economic integration organization may be Party to the Cartagena Protocol. A “regional economic integration organization” means “an organization constituted by sovereign States of a given region, to which its member States have transferred competence in respect of matters governed by [the] Protocol and which has been duly authorized , in accordance with its international procedures to sign, ratify, accept, approve or accede to it.” (Cartagena Protocol, Art. 4). One, and thus far the only, example for purposes of the Protocol is the European Union.
2 An “exporter” is “any legal or natural person, under the jurisdiction of the Party of export, who arranges for a living modified organism to be exported.” (Id., Art. 3(d)).
3 Each party to the Protocol is required to designate one or more competent national authorities that will be responsible for performing the administrative functions required by the Protocol (Art. 19.1). These functions include the receipt of notifications for purposes of the advance informed agreement procedure.
4 Id., Art. 8.1 and Annex I.
5 An “importer” is “any legal or natural person, under the jurisdiction of the Party of import, who arranges for a living modified organism to be imported.” (Id., Art. 3(f)).
6 The Cartagena Protocol established Biosafety Clearing-House to “facilitate the exchange of scientific, technical, environmental and legal information on, and experience with, living modified organisms.” It is also meant to assist the Parties in their implementation of the protocol, “taking into account the special needs of the developing country Parties, in particular the least developed and small island developing States among them, and countries with economies in transition as well as countries that are centers of origin and centers of genetic diversity.” (Art. 20; emphasis supplied)
7 The number of days that the Party of import has to wait for additional relevant information is not included
in computing the period within which the Party of import is to respond to the notifier. (Id., Art. 10.3(c)).
8 Id., Art. 6.
9 Id., Art. 7.2.
    Box 5. Procedure for Transboundary Movement of LMOs Intended for Direct Use as Food or Feed, or for Processing
The Cartagena Protocol requires a Party making a final decision regarding the domestic use (including placement in the market) of a LMO that may be subject to transboundary movement for direct use as food or feed, or for processing, to inform the other parties, through the Biosafety Clearing-House, of its decision within fifteen days therefrom.1 The notification submitted to the Biosafety Clearing-House should contain the following minimum information2:
a. The name and contact details of the applicant for a decision for domestic use;
b. The name and contact details of the authority responsible for the decision;
c. Name and identity of the LMO;
d. Description of the gene modification, the technique used, and the resulting characteristics of the LMO;
e. Any unique identification of the LMO;
f. Taxonomic status, common name, point of collection or acquisition, and characteristics of recipient organism or parental organisms related to biosafety;
g. Centers of origin and centers of genetic diversity, if known, of the recipient organism and/or the parental organisms and a description of the habitats where the organisms may persist of proliferate;
h. Taxonomic status, common name, point of collection or acquisition, and characteristics of the donor organism or organisms related to biosafety;
i. Approved uses of the LMO;
j. A risk assessment report consistent with Annex III of the Protocol
k. Suggested methods for the safe handling, storage, transport and use, including packaging, labeling, documentation, disposal and contingency procedures, where appropriate;
However, a Party may decide to regulate the importation of LMOs intended for direct use as food or feed, or for processing, under its domestic regulatory framework, provided that it is consistent with the Protocol.3 If a developing country Party has no such domestic regulatory framework, and in the exercise of its domestic jurisdiction, it may declare through the Biosafety Clearing-House that its decision prior to the first import of a LMO intended for direct use as food or feed, or for processing, will be taken according to (i) a risk assessment undertaken in accordance with Annex III of the Protocol; and (ii) a decision made within a predictable timeframe, not exceeding two hundred and seventy days.4 Failure by the developing country to communicate its decision within the said period does not imply consent or refusal to the import of the LMO, unless it is otherwise specified by such country.5
Notes
1 Cartagena Protocol, Art. 11.1.
2 Id., Annex II.
3 Id., Art. 11.4.
4 Id., Art. 11.6.
5 Id., Art. 11.7.

## What is the Codex Alimentarius Commission?

Food standard setting at the international level is done by the Joint FAO/WHO Codex Alimentarius Commission (CAC). This is an intergovernmental body established to protect consumer health and ensure fair practices in the food trade. The 23rd Session of the CAC, held in 1999, agreed to create an Ad Hoc Intergovernmental Task Force for Foods Derived from Biotechnology to develop standards, guidelines and recommendations regarding the safety and nutritional aspects of genetically modified foods.
The elaboration of food standards by the CAC follows a step-wise procedure, as shown below:
Step 1: Authorization of the elaboration of a text as new work
Step 2: Preparation of a proposed draft
Step 3: Circulation of the proposed draft for comments by governments and observers
Step 4: Consideration of the proposed draft by a Committee or a Task Force
Step 5: Provisional adoption as a draft by the CAC
Step 6: Circulation of the draft for comments by governments and observers
Step 7: Consideration of the draft by a Committee or a Task Force
Step 8: Final adoption by the CAC70
Once a text is adopted at Step 8, it is given the status of an international benchmark under the Sanitary and Phytosanitary (SPS) Agreement. While the SPS Agreement requires its Members to base their risk management measures on scientific risk assessment, Members applying recognized international standards such as those of the Codex Alimentarius are deemed to be in compliance with their obligations under the SPS Agreement. There is thus a strong incentive for governments to use Codex standards as a basis for national regulations. In doing so, they can strengthen their food control system while avoiding unnecessary trade disputes.
The Ad Hoc Intergovernmental Task Force for Foods Derived from Biotechnology has recently released, at Step 8 of the Elaboration Procedure, the “Draft Principles for the Risk Analysis of Foods Derived from Modern Biotechnology” and the “Draft Guideline for the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants”. Both documents are available at www.codexalimentarius.com, and countries wishing to regulate GM foods are well advised to review them.

## What is the Technical Barriers to Trade (“TBT”) Agreement?

The TBT Agreement is one of the agreements under the administrative supervision of the WTO. It recognizes that countries should not be prevented from taking regulatory measures necessary to pursue various “legitimate objectives” such as, inter alia, national security requirements, the prevention of deceptive practices, and protection of human health or safety of animal or plant life or the environment. Governments are, however, required to apply technical regulations and standards in a non-discriminatory manner and ensure that they do not restrict trade.
The TBT Agreement incorporates a fundamental principle of general trade law that is relevant to products of modern biotechnology: “like” products should be similarly treated. The intention is to avoid applying different regulatory measures to products with similar characteristics on the ground that they have been produced differently. This is designed to avoid arbitrary and deliberate discrimination against imported products which, although similar, may have been produced with techniques different from those used for domestically produced products. However, there is as yet no formal interpretation as to whether, under the TBT Agreement, products produced using modern biotechnology are “like” their conventional counterparts.

## What is the Sanitary and Phytosanitary (SPS) Agreement?

The SPS Agreement, like the TBT Agreement, is one of the WTO agreements. It applies to all sanitary and phytosanitary measures that may affect international trade. Sanitary and phytosanitary measures are international standards or regulations established to protect human, animal or plant health on quarantine and food safety grounds and cover such concerns as the presence of microbial contaminants, toxins, heavy metals and pesticide residues in food and quarantine risks posed by pests weeds and pathogens that are applied domestically.
In the context of trade in agricultural products, these measures are to be applied only to the extent necessary to protect human life or health and “to protect human life or health from the risk arising from additives, contaminants, toxin or disease causing organisms in foods.” The SPS Agreement removes the right of countries to arbitrarily restrict access to markets on health and safety grounds. It also calls on members to harmonize sanitary and phytosanitary measures on a global basis by adopting international standard guidelines and recommendations, where these exist. Sufficient scientific evidence must be provided if members wish to maintain SPS measures at levels above relevant international standards.
The scientific requirement of the SPS Agreement is important because it provides a more objective approach in determining what is a justified trade restriction and what is hidden protectionism. On the other hand, the agreement may seem inadequate to tackle restrictions introduced on the basis of consumer sentiments in relation to food production methods such as genetic engineering.
When scientific evidence is unavailable or insufficient for a final judgment about the safety of a product or process to be made, Article 5.7 of the SPS Agreement explicitly allows WTO member states to take precautionary measures based on available pertinent information. Members are, however, obliged to seek additional information so that a more objective evaluation of the risks related to the relevant product or process can be made within a reasonable period of time.