2.2. Genetic engineering and biotechnology in industry

JANET BELL

Broadly defined, biotechnology refers to any technique which uses living organisms to make or modify a product. It includes the spectrum of new and old technologies, from the beer-brewing techniques developed by the Sumerians in the Middle East in 7000 BC to the high-tech gene transfer techniques that graft chicken genes into potatoes today. Traditional biotechnologies are used in the production of many common foodstuffs, such as cheese, salami, yoghurt, beer and bread. These all rely on the addition of genetic material in the form of living organisms (bacteria or yeasts) to milk or grains in order to transform them into new products.

Commercial biotechnology today comprises a range of different techniques including tissue culture, cell fusion, enzyme and fermentation technology, embryo transfer and, increasingly, genetic engineering. The techniques make it possible to modify more and more profoundly the process of life itself. The history of the new biotechnologies is a short one, born in university laboratories and public research institutions, and only transported to the corporate sector in the late 1970s and early 1980s. However, industry's brief involvement has had a fundamental impact on the priorities and direction of agricultural and medical research around the world, and it is also set to change the nature of production systems for a vast number of essential products such as foods, chemicals and medicines.

Tubocurarine, an important muse/e relaxant drug used in open heart surgery, is derived from the curare vine from the South American rainforest. (WWF/Royal Botanic Gardens, Kew)

Genetic diversity has always been a key raw material in agricultural and medical research. At least 7000 medical compounds in the Western pharmacopoeia are derived from plants, and plant-derived products account for a conservative estimate of $40-50000 million in pharmaceutical sales globally. Roughly one-half of the gains in US agricultural yields from 1930 to 1980 can be attributed to genetic diversity's contribution to crop breeding activities. But whereas previously only close relatives of crops could be used in breeding programmes, now the genes from the world's entire genetic pool can be used.

The pharmaceutical industry

Natural products are hack in fashion in the pharmaceutical industry. There are three main reasons for this. Firstly, the development of more efficient screening techniques has increased 100-fold the speed with which chemicals can be tested. Although only about one in 10 000 chemicals yields a potentially valuable 'lead', these new techniques have made large natural product screening programmes affordable. Secondly, companies have realized that by tapping into the traditional medicinal knowledge of indigenous communities they can greatly increase the probability of finding a commercially valuable drug and thus dramatically reduce research costs. And thirdly, there is a growing demand in industrialized countries for 'natural' medicines.

Recent policy decisions made by the US National Cancer Institute (NCI) give an indication of the importance now attached to medicinal plants. In 1980, NCI suspended a 20-year programme of collecting medicinal plants. In 1986, it renewed and enlarged the programme when the opportunities presented by the new biotechnologies became apparent. Between then and the end of 1992 the NCI paid for the collection of 23 000 plant samples of 7000 species, almost all of which came from the South. Table 2.1 outlines some of the main actors and their current bioprospecting interests.

One of the fastest-growing applications of genetic engineering is gene therapy, which involves manipulating a person's genetic makeup for therapeutic purposes. Along with plants and animals, human genes are now an important resource for industry (see Chapter 5). Two-thirds of all biotechnology companies are focusing on the medical applications of biotechnology, and only one in 10 is applying biotechnology to food and agriculture. Nevertheless, the application of biotechnology to food and farming is likely to have a much more profound impact on people's livelihoods, lifestyles and the environment than other applications of biotechnology, at least in the medium term.

Table 2.1. Selected companies and their bioprospecting activities

Adapted from Pirating Indigeneous Plants, RAFI and Indigenous Peoples 'Biodiversity Nework, RAFI Occasional Paper Series Vol. 1, No. 4, November 1 994

Genetic engineering in agriculture

Genetic engineering speeds up dramatically the process of breeding for desirable traits in plants and animals - improvements that would take up to 20 years in conventional breeding can be achieved almost overnight. It also enables the creation of life-forms that would never come into existence in nature, as genes from completely different species can be exchanged and transplanted (see Table 2.2). In this way, genetic engineering provides us with the means not just to accelerate evolution, but to supersede it altogether.

Table 2.2. Sources of new genes in transgenic crops

Information compiled from applications to the US Department of Agriculture to field test engineered plants (Union of Concerned Scientists, 1993)

The first genetically engineered foods are just beginning to enter our lives. Scientists have succeeded in producing engineered versions of most of the world's major food and fibre crops - including rice, potato, soybean, corn and cotton - as well as numerous fruits, vegetables and trees. More than 60 plant species have been engineered in this way, most of which have moved from the laboratory to the field testing stage, and are now starting to reach the market place. In May 1994, the first of these, a genetically engineered rot-resistant tomato, was launched into US supermarkets. In spring 1994, the first commercial transgenic organism entered European markets: a herbicide-resistant tobacco plant.

It's not just crops and fruits that are the focus of new age biotechnology. Genetically engineered bovine growth hormone (rBGH), which increases milk production in cows, was approved in the US in 1993. While the milk produced has been judged safe for humans, the health impact on the cows can be significant (see Box 2.1).

These first product launches illustrate the priorities of research and development in biotechnology. These were: a delayed ripening tomato that benefits food processing and transportation firms rather than consumers; a growth hormone that has a serious deleterious effect on animal health; and a tobacco plant that encourages increased use of a weed killer known to be a health hazard to plants, animals and humans.

Research priorities in the agrochemical industry

Biotechnology is often touted as promising tremendous benefits in the form of healthier food and low-chemical agriculture, and even as the solution to the problem of world hunger. Through genetic engineering, plants can be made to fix nitrogen, thereby reducing the need for nitrogen fertilizers, and to protect themselves against the pests that plague them, thereby removing the need for environmentally-damaging chemical pesticides. Food crops engineered to be more drought-resistant could improve food security in arid regions.

While some investment is going into these potentially useful fields, research priorities appear to be skewed away from the needs of the environment, farmers and consumers, and geared heavily towards corporate interests. So far, the lion's share of genetic engineering activity in crops is devoted to the production of crops tolerant to chemical weed killers, technically known as herbicides. Between 1986 and 1992, 57% of field trials of transgenic crops were for herbicide resistance. Such crops can withstand both high doses and new kinds of chemicals, which is likely to lead to increased rather than decreased herbicide use in agriculture.

Not surprisingly, chemical companies and their collaborators are the major sponsors of this work. For example, the US biotech company, Calgene, in collaboration with the multinational chemical company Rhone-Poulenc, is seeking US approval to market cotton genetically engineered to be resistant to Rhone-Poulenc's herbicide bromoxynil. Ordinary cotton is killed by the herbicide, which also causes birth defects in animals and has been classified as a developmental toxicant for humans. Widespread adoption of this new cotton could double or triple the current use of bromoxynil in US agriculture alone.

The agrochemical industry feels an urgent need to boost sales, which reached $25 200 million worldwide in 1992. In 1992 only Monsanto, Du Pont and American Cyanamid could boast an increase in sales over 1991.7 In 1993, only four of the top ten companies saw any sales growth (see Table 2.3). The slowing of sales growth has been attributed to recession, increased research costs due to increased environmental controls over product development, and farm policy reforms in the North. Consequently, companies are looking to the rest of the world, and Asia in particular, to boost their foundering profits.

Aside from herbicide-tolerance, other applications include reducing food-processing costs, improving the transportability and increasing the shelf life of foods, and improving pest resistance. Selecting for processing traits follows traditional plant breeding down the path that has brought us tough but tasteless tomatoes and apples that today dominate the grocery shelves. Even the more laudable pursuit of pest resistance, which offers potential benefits to both farmers and consumers, can create more problems than it solves, as illustrated by the case of Bt toxin (Box 2.2). The introduction of Bt toxin genes into plants took several years and cost between $1.5 and $3 millions. In early 1995 the US granted limited registration for genetically-engineered Bt corn, cotton and potatoes. Yet the future of Bt toxin is already being threatened by the very feature that makes it so effective.

Table 2.3. Global agrochemical sales and ranking of the top ten companies, 1993

Sources: AGROW No 214, August 19, 1994; Seedling, December 1993

Pest resistance may be a useful application for genetic engineering, but there are often better ways of accomplishing the same goal: working with nature is often more effective than trying to stamp on it. This is the foundation on which agroecology is built. The agroecological approach addresses the health and dynamism of the whole farming ecosystem, rather than focusing on the output of a particular crop or attacking a single pest. Its strategy is defined by closely examining the relationships between the different elements, living and non-living, of the ecosystem and following a path that achieves the productive ends desired without compromising or unbalancing the ecosystem.

Agroecology encourages the use of techniques such as intercropping and integrated pest management, which do not aim to eradicate pests altogether, but to keep their populations low or to tempt them away to a more appealing food source. Crop rotations and intercropping may, for example, be more effective in controlling a range of pests by breaking the cycles through which they achieve destructive population levels. Rotations are effective against a wide range of pests, whereas chemical pesticides and genetic manipulations tend to be pest-specific, requiring a complex cocktail of elements to protect a plant fully. The agroecological and biotechnological approaches to agriculture are summarized in Table 2.4.

Table 2.4. Biodiversity as a productive force: two agendas

Feeding the world

Biotechnology is often presented as the answer to feeding the world's burgeoning population. But very little research and field testing is allocated to meeting this challenge. Given the expensive nature of the technology, this is not surprising. Biotechnology companies cannot develop products for people who cannot pay for them: most of the world's hungry are too poor to buy traditionally produced crops, let alone biotech's designer collection.

One partial solution is to provide developing countries with the genetic engineering tools they need to create their own transgenic crops. This approach is being considered by the parties to the Biodiversity Convention as a way of compensating the South for the contribution of its genetic heritage to the benefit of Northern countries, companies and consumers. Agreeing terms and conditions of such exchanges is a great challenge, however, and industry is likely to try to ensure that it retains a strong influence in the application of such technologies and to share the benefits that derive from them.

In 1992, Monsanto gave Mexican scientists virus-resistant genes from potatoes for introduction into local potato varieties. The agreement was made on the condition that the transgenic potatoes were only to be sold for consumption in Mexico, where potatoes are a small part of the diet. According to Monsanto, We are aiming to help the subsistence farmer to feed his family - they don't export potatoes, they eat them. We wanted to leave the door open for us to participate in the marketplace with Mexican farmers who are in it for profit.

Given the limited interest shown by companies and universities in crops that would help Southern communities, genetic engineering is likely to play a minor role, at best, in the coming crisis of food production. The resources available for research into crops like cassava and sorghum will continue to be small compared to those devoted to corn, cotton and soybeans. Many of the IARCs are struggling to decide how many of their resources should be devoted to genetic engineering techniques, given the high investments required which can often be made only at the expense of other areas of research. At IRRI, for instance, four new biotech laboratories are being set up to work specifically on rice. Bt toxin is a major focus of research, but some staff fear that the toxin may not ultimately be useful in farmers' fields because of the resistance problems described in Box 2.2 (p. 44). Critics argue that Bt research is being undertaken widely in the public and private research arenas, and that IRRI would be better advised to examine ecological approaches to rice-stem borer control, which are largely being ignored.

Even where research does yield new varieties of crops that show promise for Southern farmers, productivity is only one factor in the complicated equation of world hunger. Trade, agricultural subsidies and unsustainable agricultural practices are also important causes of hunger. Developing higher-yielding crops without addressing these other issues will ultimately have little impact.

According to the US-based Union of Concerned Scientists, 'The notion that the products of genetic engineering can somehow single-handedly solve the problems of world hunger is a dangerous misconception. Genetic engineering may have a role to play in meeting the challenge of world hunger, but it will not serve as a technological 'fix' nor compensate for decades of environmental abuse and misguided agriculture.'

Another consequence of commercial biotechnology is the dissection of organisms into their genetic components and their removal from the natural world altogether. There is increasing interest in transferring the production of commodities from the fields, forests and plantations of the South to the laboratories of the North. This has two major ramifications. Firstly, it reduces the perceived value of the indigenous plant or crop, reducing the need for its conservation, which has broader implications for biodiversity as a whole. Secondly, it shuts down important export markets for Southern commodities, thus threatening the livelihoods of millions of plantation workers and farmers. Commercial production of the West African sweetener, thaumatin, is a good example of the impact such production switches can have, at least in the short term. Likewise, commercial production of vanilla may before long eliminate the need for both the vanilla orchid and the vanilla farmer. There is a wide variety of high-value plant-derived products that could be affected in this way. Calgene has engineered a variety of rape-seed (canola) which contains a high content of laurate, a fatty acid used in the manufacture of soaps and detergents. The traditional sources of laurate are palm kernel and coconut oils, which are an important export for Southeast Asian nations. Thus these countries may soon start to lose income they depend on. Farmers in the state of Georgia in the USA are already growing the first commercial transgenic rape-seed crop.

In some cases, however, given the ever-decreasing prices of (and diminishing returns from) the major commodities like sugar, cocoa and coffee, exclusion from the global market could be a blessing in disguise for Southern countries. This situation could provide an opportunity to redirect food production strategies towards meeting local needs, rather than overloading the North's dinner plate.

It is not just Southern farmers' livelihoods that are threatened by biotechnology. If industrial agriculture follows its current course, Northern farmers will also be threatened as food production shifts to laboratories. Huge industrial vats of bacterial soup producing sugars, oils and cellulose are already providing the raw materials for the synthetic food industry, while research focuses on new 'food alchemy', the packaging of industrial chemicals into mouth-watering delicacies, and exploring the 'gustatory perception of smell' or taste. Instead of global markets for maize, cocoa, coconut oil or soybeans, we will soon be dealing with market prices for starches, oils and proteins.

Environmental risks of transgenic crops

Genetically engineered crops are not necessarily inherently dangerous, but the introduction of new traits (such as resistance to cold, drought, etc.) through genetic engineering will necessarily result in unpredictable interactions with the environment into which the plant is introduced. Transgenic plants are likely to be less predictable than those produced by traditional breeding techniques, because the genes introduced are from a completely different species rather than from a related variety. New genes may not be subject to the same mutual constraints as those that have evolved as a group.

Another risk arises from the nature of the new trait introduced. Many transgenes control traits that are ecologically advantageous to plants. Resistance to cold, disease or herbicides enables plants to overcome obvious limits on population growth, which can affect the balance of the local ecosystem. In addition, transgenes producing toxins may affect a wider target audience than desired. For example, a genetically engineered plant virus containing a scorpion-derived toxin gene is being field tested in the UK. It is intended to kill the cabbage white butterfly larva, but its host range is known to be wide, and includes rare and protected moth and butterfly species.

New genes introduced into a plant are subject to the normal rules of genetic drift that occur in the process of natural selection and reproduction. And since the introduced traits tend to be determined by one or two genes (reflecting biotechnology's current limitations), they can readily be transmitted into wild populations. Thus, the new genes join the gene flows that occur throughout the whole ecosystem in which the plant lives.

Movement of these genes into wild relatives of crop plants with which the crop can cross-fertilize is almost bound to occur. Many of the genes introduced will come from animals and micro-organisms which would never have found their way into plants by natural processes. Currently the impact of this on ecosystems is extremely poorly appreciated or understood.

Health risks of genetic engineering

Some genetically engineered organisms are made with viral or transposon vectors that have been artificially modified to become less species-specific. Since viruses and transposons can cause or induce mutations, there is concern that enhanced vectors could be carcinogenic to humans, domestic animals and wild animals. There are also fears that once-familiar foods may become allergenic or metabolically destabilizing through genetic engineering. Allergenic effects could he carried by the transgene or be stimulated by imbalances in the chemistry of the host plant or organism. Strong evidence for a causal link has already been observed in the US and other countries related to an epidemic of eosinophilia-myalgia syndrome (EMS). By June 1992, 1512 cases and 38 deaths had been reported. This disease is caused by a hyper-sensitivity reaction of the immune system which appears to have been linked to ingestion of a batch of genetically engineered L-tryptophan, an amino acid found naturally in various foods.

Innocent until proven guilty

Assessing the risks of releasing genetically modified organisms (GMOs) is extremely difficult since the flow of novel plant, animal and microbial genes into agricultural and wild ecosystems defies any natural processes. Following historical legal precedents, regulation favours placing the burden of proof on proving the harmful impact of GMOs rather than their benignity. Many NGOs argue that the burden of proof should be reversed for GMOs because the stakes are so high. Unlike faulty computers or washing machines, GMOs cannot be recalled if they go wrong. Past experiences with cases like DDT and thalidomide do not engender strong faith in leaving risk assessment in the hands of industry.

Moving towards a biosafety protocol

Since the mid-1980s, most industrialized countries have adopted regulations concerning the safe handling and use of genetically engineered organisms. Some, such as the US, simply adapted their regulatory framework by adjusting it to the special risks linked with the new genetic engineering techniques. Others, like the European Union and most of its member states, established new laws covering the contained use as well as the deliberate release of GMOs. In the South, however, biosafety regulation is virtually non-existent. As a consequence, an increasing number of companies from the US and Europe are choosing to conduct releases of GMOs in countries which have no regulations in place (see Table 2.5). For example, Calgene tested its 'Flavr Savr' tomato in Mexico and Chile, and insecticide-producing cotton plants in South Africa. Monsanto conducted field trials of its genetically engineered soybean in Puerto Rico, Costa Rica, Argentina and Belize. As can be seen from Table 2.5, the products being tested do not deal with the pressing problems of agriculture in those countries.

Table 2.5. Field with transgenic plants in Latin America (1980 92)

Source: Seedling., Dec. 1994, after Jaffe (1993)

Only two developing countries, India and the Philippines, have any sort of biosafety system in place. Such a regulatory void can lead to biotechnological colonialism, whereby Southern lands are used to carry out field tests in conditions that would never be allowed in the North. Simply extending the regulations from the North to the South is not enough, because the impact of GMOs depends on the agroecological environment. Genetically engineered cold-tolerant potatoes may be approved in the US if it can he shown that there is no danger of gene flow to wild relatives. By contrast, the presence of many local varieties and sexually compatible wild potato relatives in Peru (a centre of diversity for potatoes) means that transgenes are more likely to move from the engineered crop to wild relatives.

The need for internationally harmonized safety regulations was recognized in the Biodiversity Convention. An expert panel appointed to address the issue recommended the adoption of a legally binding instrument. A few developed country representatives, led by the US, opposed the creation of any protocol, adopting the industry position that such action should be based on 'sound scientific evidence' rather than what they consider to be 'misrepresentations and distortions'. The vast majority of countries, however, strongly supported the development of a biosafety protocol.

At the second meeting of the Biodiversity Convention's Conference of the Parties, in late 1995, Northern delegations were pushing to limit the protocol to dealing with 'transboundary transfer of LMOs [living modified organisms],' while Southern delegations were in favour of a protocol on biosafety in the field of the safe transfer, handling and use of LMOs. It was agreed that there would be a biosafety protocol and, although the precise terms of reference were still to be determined, it appeared that the North had won out. The conference called for a negotiation process to develop in the field of safe transfer, handling and use of living modified organisms, a protocol on biosafety, specifically focusing on transboundary movement of any LMO resulting from modern biotechnology that may have adverse effect on the conservation and sustainable use of biological diversity.

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