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Synthesis/Regeneration 25   (Summer 2001)

Engineering Plants to Manufacture
Pharmaceuticals and Industrial Enzymes

Biohazards: The Next Generation?

by Brian Tokar, Institute for Social Ecology

With the worldwide rejection of genetically engineered foods, the biotechnology industry is scrambling to develop a new generation of products that can might someday be seen as advantageous for consumers and beneficial to humanity. This is the primary motivation, of course, behind the massive PR campaign to sell the benefits of so-called "golden" vitamin-A rice. Even as the claimed health benefits of this invention have been widely discredited—and activists in the global South have been in the forefront of pointing out that such inventions will do nothing to help people reclaim the ability to feed themselves—the mainstream press continues to tout this rice as evidence that biotechnology will someday feed the world. This is only the beginning.

The widely-touted "next-generation" of genetically engineered products are quite diverse in nature. They include salmon that can reportedly grow up to twice as fast as non-engineered varieties, with serious consequences for native ecosystems once these "super-fish" escape from coastal fish farms. Poplar, eucalyptus and pine trees are being genetically engineered to grow faster and more uniformly, tolerate high doses of herbicides, and become more suitable for chemical processing into paper pulp. Here, the potential ecological consequences are magnified many-fold compared to the already well-known hazards of GE varieties of annual food crops, due to trees' longer lifespan, the more persistent spread of their pollen, and effects on countless other forest-dependent species. Researchers are even claiming to be ready to release genetically engineered insects on an experimental basis. Whether they are engineered to administer vaccines, or weakened strains intended to compete against pathological insects and crop pests, it is extremely unlikely that such creatures could ever be satisfactorily controlled. The potential problems are reminiscent of the genetically engineered Australian mice that were hoped to facilitate population control due to reduced reproductive ability, but instead annihilated an entire population.

Another relatively recent development is the engineering of plants to produce a variety of pharmaceuticals and industrial chemicals. Nearly everyone has read of efforts to engineer bananas that might someday be used to administer vaccines; as with countless other applications of genetic engineering, the hype is far more convincing than the reality. Still, companies like Monsanto, DuPont and Dow have been actively exploring experimental methods for producing vaccine components, human antibodies and various industrially useful proteins in tobacco, corn and potato plants. One company, the Texas-based ProdiGene, has been collaborating with Stauffer Seeds to produce eleven different proteins in genetically engineered plants on a commercial scale. Along with the efforts of companies like the Massachusetts-base Genzyme to engineer animals as "bioreactors" for drug production, this represents a whole new sphere of biotechnology applications—and potentially horrific problems as well.

On one level, the new "bioreactor crops" present many of the same potential environmental problems as other genetically engineered crop varieties, particularly if they are to be grown outdoors on a large scale. Most noteworthy are problems of cross-pollination, and unknown deleterious effects on beneficial insects, soil microbes and other native organisms. But additionally, we may soon see biologically active enzymes and pharmaceuticals, usually only found in nature in minute quantities—and usually biochemically sequestered in very specialized regions of living tissues and cells—secreted by plant tissues on a massive commercial scale. The consequences may be even more difficult to detect and measure than those associated with more familiar GE crop varieties, and could escalate to the point where those now-familiar problems would begin to pale by comparison.

..."bioreactor crops" present…problems of cross-pollination, and unknown deleterious effects on beneficial insects, soil microbes and other native organisms.

There are also potentially severe public health consequences. As commercial grain distributors have proved unable to reliably sequester such a relatively well-characterized product as Aventis' Starlink corn, what steps could be reliably taken to prevent the accidental commingling of crops engineered for chemical production into the rest of the food supply? British proponents of this technology have already proposed ameliorating the high cost of purifying specific proteins from plants with income obtained by extracting food products such as oils, starches and flours from these same crops. Anyone want some pharmaceutical residues or industrial enzymes in their corn flakes or taco shells?

Concerns about the public health and environmental consequences of these crops are exacerbated by their wide range of very high-level biological activities. Products being actively researched for plant-based production include blood coagulants, proteases and protease inhibitors, growth promoters, neurologically active proteins, and enzymes that modify the structure and function of other biologically important compounds, as well as monoclonal antibodies and viral surface proteins potentially useful for vaccination. Large scale releases of antibodies and viral antigens may trigger unexpected allergic or autoimmune reactions in some people.

Large scale releases of antibodies and viral antigens may trigger unexpected allergic or autoimmune reactions in some people.

Even the purported benefits of plant-produced vaccines are cast in doubt by the evidence. One problem is the well-documented phenomenon of oral tolerance: a concerted loss in vaccine efficacy that often follows the administration of antigens through a mucous membrane. Hazardous chemicals such as cholera toxin are often needed as cofactors to increase the effectiveness of oral vaccines. Even the proponents of this technology have cited the contamination of pharmaceuticals with pesticide residues as a significant problem.

The active collaboration between ProdiGene and Stauffer Seeds has already brought several products of this technology to market in the US, and their products serve to highlight the potential hazards of plants engineered to produce commercial proteins. Stauffer is actively contracting with farmers to grow corn containing the genes for 3 or 4 specific enzymes, 3 vaccines, a protein-based sweetener, a proprietary "Therapeutic Agent," and 2 other biologically active chemicals. Three of their products, avidin, beta-glucuronidase and aprotinin (a protease inhibitor commonly used by surgeons), have been produced in sufficient quantities to be sold through a commercial chemical supplier, the St. Louis-based Sigma Chemical Company.

Avidin is a protein that naturally occurs in raw egg whites. While Sigma markets it for use in medical diagnostic kits, it is also used as an insect growth inhibitor and is being investigated as a next-generation biopesticide. Avidin binds to biotin, an important B-vitamin, and prevents its absorption across the intestinal mucosa. It also causes a type of vitamin B deficiency in some people who consume raw egg whites.

There are contradictory reports as to whether beta-glucuronidase was produced by Stauffer in 2000, but it appears to have been available from them for a number of years. This enzyme reverses a biochemical reaction that helps render irritant molecules soluble. This added solubility helps to facilitate the detoxification and elimination of compounds as diverse as hormones, antibiotics and opiates. In the presence of this enzyme, potential toxins are freed from the molecular complex that enables their proper excretion. One can only speculate on the consequences of elevated levels of such compounds being released into the open environment.

Stauffer's professed goal is to maximize production of these and other compounds via both foreign and domestic production of transgenic corn, allowing for three growing cycles per year. According to their web site, production is currently under way in South America, the South Pacific, and the Caribbean, as well as within the continental US (www.staufferseeds.com/0405econ.htm). As South America is the center of biodiversity for maize, the potential for widespread disruptions of indigenous wild relatives may be quite severe.

As South America is the center of biodiversity for maize, the potential for widespread disruptions of indigenous wild relatives may be quite severe.

Other companies at the forefront of turning plants into chemical factories include the Virginia-based CropTech, which has produced pharmaceuticals and human enzymes in tobacco, with several products already in clinical trials. The San Diego-based EPIcyte has partnered with Dow Chemical to develop and produce experimental human antibodies in plants, as well as a topical contraceptive and a microbicide that is purported to be active against HIV. Monsanto's Integrated Protein Technologies subsidiary is seeking contracts with various clients to produce commercial quantities of various proteins in corn, tobacco and soybean plants. They claim to be able to produce several metric tons of any appropriate protein within a three-year period. Several other companies in the US, Canada and in France are also actively exploring these techniques.

Taken at face value, the promises offered by many of these companies may seem impressive. They suggest that they will make therapeutically useful agents much more widely available at considerably lower cost. If this is done solely in isolated greenhouses, pollen is entirely contained, and byproducts of this process completely isolated from the food supply, the advantages might someday outweigh the hazards in several instances. But according to Carole Cramer, the founder of CropTech, some products under consideration would require thousands or even hundreds of thousands of acres, planted at densities (in the case of transgenic tobacco) of 50,000 to 100,000 plants per acre, to supply the current market for these proteins. Given the recent track record of the biotechnology industry in aggressively promoting their products at all costs, denying all potential hazards, and refusing to sequester potentially harmful crops, the likelihood of the best-case scenario coming to pass appears extremely slim.

Brian Tokar's latest book is Redesigning Life: The Worldwide Challenge to Genetic Engineering (Zed Books, 2001). A longer, fully referenced version of this paper will be available this summer as an Occasional Paper of the Edmonds Institute (www.edmonds-institute.org).

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