Dr. Mae-Wan Ho, Reader in Biology at the Open University, B.Sc. (First Class) 1964, and Ph. D. 1967, H K University; more than 30 years in research and 22 years teaching experience; nearly 200 publications covering human biochemical genetics, molecular genetics, evolution, developmental biology, and biophysics. Awards include, Chan Kai Ming Prize for Biological Sciences (HK) 1964: Fellow of the National Genetics Foundation (USA) 1971-1974; Vida Sana Award (Spain) 1998; Guest of Honour in Women of the Year Luncheon & Assembly (UK) 1998. From 1994, Scientific Advisor to the Third World Network and other public interest organizations on biotechnology and biosafety. Debated issues in the United Nations, the World Bank, the European Parliament, in the UK, USA and many other countries all over the world. Author of many papers and reports for the public and for policy-makers, frequent broadcaster and public lecturer. Recent publications relevant to genetic engineering:
Genetic Engineering Dream or Nightmare? Mae-Wan Ho, Gateway Books, Bath, UK, 1998; (revised, 2nd. edition, 1998).
Gene Ecology and Gene Technology of Infectious Diseases, Mae-Wan Ho et al, Microbial Ecology in Health and Disease 10, 33-59, 1998.
Genetic Engineering and Infectious Diseases, Mae-Wan Ho et al, Third World Network, Penang, 1998.
Fatal Flaw in Food Safety Assessment: The FAO/WHO Joint Biotechnology & Food Safety Report, Mae-Wan Ho and Ricarda A. Steinbrecher, Third World Network, Penang, 1998.
Fatal Flaw in Food Safety Assessment: The FAO/WHO Joint Biotechnology & Food Safety Report, Mae-Wan Ho and Ricarda A. Steinbrecher, Environmental and Nutritional Interactions (in press).
A. General remarks Ms Shannon Coggins, is within her rights as a citizen of civil society to draw attention to information which is already given in the list of ingredients on the packet. The word "contamination" accurately describes the admixture of genetically modified with non-genetically modified soya beans in the "soya protein mince" used. The contamination arose from the lack of segregation in shipment and processing of the soya beans. In no way can it be construed to result from Ms Coggins' action. Ms Coggins was motivated by her concern over the health hazards of the genetically modified "soya protein mince", a concern that is fully justified on the basis of existing scientific evidence. She was, therefore, acting responsibly in drawing attention to the hazards for the benefit of other consumers.
B. Genetic engineering is a new departure from conventional breeding and introduces significant differences
1. In conventional breeding, closely related species are cross-fertilized, and plants with the desired characteristics are selected from among the progeny for reproducing, and the selection is repeated over many generations. Genetic engineering bypasses reproduction altogether. It makes use of infectious agents to transfer genes horizontally from one individual to another (as opposed to vertically, from parent to offspring); so that genes can be transferred between distant species that would never interbreed in nature. For example, human genes are transferred into pig, sheep, fish and bacteria. Fish genes are transferred into tomatoes. Completely new, exotic genes, can therefore be introduced into food crops.
2. Natural infectious agents exist which can transfer genes horizontally between individuals. These are viruses and other pieces of parasitic genetic material, called plasmids and transposons, which are able to get into cells and then make use of the cell's resources to multiply many copies or to jump into (as well as out of ) the cell's genome. The natural agents are limited by species barriers, so that for example, pig viruses will infect pigs, but not human beings, and cauliflower viruses will not attack tomatoes. Genetic engineers make artificial vectors by combining parts of the most infectious natural agents, and design them to overcome species barriers, so the same vector may now transfer, say, human genes, which are spliced into the vector, into the cells of all other mammals, or cells of plants. Once inside the cell, the artificial vector carrying the foreign gene(s) can then insert into the cell's genome, and give rise to a genetically engineered organism.
3. Typically, foreign genes are introduced with strong genetic signals - called promoters or enhancers - to boost the expression of the genes to well above the normal level that most of the cell's own genes are expressed. There will also be selectable "marker genes" introduced along with the gene(s) of interest, so that those cells that have successfully integrated the foreign genes into their genome can be selected. The most commonly used marker genes are antibiotic resistant genes, which enable the cells to be selected with antibiotics. These marker genes often remain in the genetically engineered crops.
C. Health hazards arising from genetically engineered foods in general
1. There are three main sources of hazard to health arising from genetically engineered foods in general: those due to the new genes and gene products introduced; unintended effects in the nature of the technology and interactions between foreign genes and host genes; those arising from the horizontal spread of the introduced DNA.
2. New genes and gene products are introduced into our food that we have never eaten before, and certainly not in the quantities produced in the genetically engineered crops, where they are equipped with strong promoters to express at high levels. The long term impacts of these genes and gene products will be impossible to predict, particularly as the products are not segregated and there is no post-market monitoring. There are already signs that some of the gene products can harm non-target species. For example, many plants are engineered to express a bt-toxin from the soil bacterium, Bacillus thuringiensis, targetted against specific insect pests. But they actually harm beneficial insects. Thus, genetically engineered bt-cotton killed 30% of the bees in the fields when field-tested in Thailand (see Ho et al, 1998, and references therein). Harmful effects can even go up the food-chain. Lacewings fed on pests that have eaten genetically engineered bt-maize took longer to develop and were two to three times more likely to die (Hilbeck et al, 1997).
3. The technology of genetically engineering organisms is hit or miss, and not at all precise, contrary to misleading accounts intended for the public, as it depends on the random insertion of the artificial vector carrying the foreign genes into the genome. This random insertion is well-known to have many unexpected and unintended effects including cancer, in the case of mammalian cells (Walden et al, 1991; Wahl et al, 1984; see also entries in Kendrew, 1995). Furthermore, the effects can spread very far into the host genome from the site of insertion (recently reviewed by Doerfler et al, 1997). This is attested to by the high failure rates in making transgenic animals, and high levels of gross deformities among the "successes" (see Ho et al, 1998 and references therein). Unexpected and unintended effects will also arise from interactions between foreign genes and genes of the host organism, as no gene functions in isolation. Among the unintended effects relevant to food safety are new toxins and allergens, or changes in concentrations of existing toxins and allergens. In 1989, a genetically engineered batch of tryptophan killed 37 and made 1500 ill, some seriously to this day (Mayeno and Gleich, 1994). A Brazil nut allergen was identified in soya bean genetically engineered with a brazil nut gene (Nordlee et al, 1996).
4. The same cellular mechanisms that enable the vector carrying the foreign genes to insert into the genome can also mobilize the vector to jump out again to reinsert at another site or to infect other cells. Secondary horizontal tranfer of transgenes and antibiotic resistant marker genes from genetically engineered crop plants into soil bacteria and fungi have been documented in the laboratory (Hoffman et al, 1994; Schlutter et al, 1995; Gebbhard and Smalla, 1998). Plants engineered with genes from viruses to resist virus attack actually showed increased propensity to generate new, often super-infectious viruses (Vaden and Melcher, 1990; Lommel and Xiong, 1991; Green and Allison, 1994; Wintermantel and Schoelz, 1996). Thus, genetically engineered crops may spread antibiotic resistant genes to pathogenic bacteria in the environment as well as to bacteria in the gut of animals including human beings (see next paragraph). They may also contribute to generating new viral pathogens. This is particularly relevant in the light of the current world health crisis in drug and antibiotic resistant infectious diseases, and evidence indicating that horizontal gene transfer has been responsible for spreading drug and antibiotic resistance genes as well as creating new pathogens (see Ho et al, 1998).
5. In addition, there is evidence that DNA is not broken down rapidly in the gut as previously supposed. DNA from a virus fed to mice has been found to resist digestion in the gut. Large fragments passed into the bloodstream and into white blood cells, spleen and liver cells. In some instances, the viral DNA may integrate into the mouse cell genome (Schubbert et al, 1994; 1997). Viral DNA is now known to be more infectious than the intact virus, which has a protein coat wrapped around the DNA. For example, intact human polyoma virus injected into rabbits had no effect, whereas, injection of the naked viral DNA gave a full-blown infection (see Traavik, 1995; Ho et al, 1998; Ho, 1998a, 2nd ed., Chapter 10). Many kinds of artificially constructed vectors are found to infect mammalian cells (see Ho, 1998a Chapter 10, Ho et al, 1998). Thus, the foreign DNA introduced by artificial vectors into genetically engineered plants may constitute a serious health hazard by itself. As mentioned in paragraph C.3, integration of foreign DNA into cells are well-known to have many adverse effects including cancer. While in the gut, DNA containing antibiotic resistance genes may also spread to gut bacteria.
D. Health hazards from the genetically engineered soya
1. Health hazards from the genetically engineered soya have been considered in detail in a Report by the Ecological Institute of Freiburg (Oekoinstitut Freiburg, 1997). The Report concludes that the tests carried out by Monsanto failed to exclude significant health risks from the genes and gene-products introduced, and from unintended changes in allergenicity of the soya proteins. In addition, evidence of adverse health impacts of glyphosate and glyphosate residues and of the effects of glyphosate on phyto-oestrogen levels of the genetically engineered soya have not been addressed.
2. The processing involved in producing "soybean protein mince" from transgenic protein may leave non-protein contaminants including DNA and metabolites that could cause harm. No tests on the contaminants of the "soybean protein mince" have been reported.
3. The genetically engineered soya used in the product contains genes from a virus, a soil bacterium and from petunia, none of which has been in our food before. The main foreign protein expressed, which makes the plant resistant to glyphosate, is from a soil bacterium, Agrobacterium sp. It is engineered into the soya plant in a new form (CP4EPSPS), and its expression is boosted by a strong promoter from the cauliflower mosaic virus to a high level of approximately 0.2% of the seed protein. The novel protein is unlike any other protein that human beings have eaten. And there is no reliable method for predicting its allergenic potential. Allergic reactions typically occur only some time after the subject is sensitized by initial exposure to the allergen.
4. Soya beans are known to have at least 16 proteins that can cause allergic reactions, which differ for different ethnic groups. The tests applied by Monsanto were not sufficiently discerning and wide-ranging to reveal changes in those proteins, or indeed other proteins that may also be allergenic. In one test, a major allergen, trypsin-inhibitor, was found to be 26.7% higher in transgenic soya beans (Padgette et al, 1996), despite the authors' claim that the genetically engineered soya bean is "equivalent" to that of conventional soya bean. Trypsin-inhibitors also have anti-nutritional effects in reducing growth rate of rats (Kakade et al, 1973).
5. The feeding studies carried out by Monsanto, which also did not use transgenic soya beans sprayed with glyphosate, nevertheless revealed significant increases in milk fat in cows fed transgenic soya beans compared to controls, and a number of other differences including lower body weights and cumulative body weight gains in male rats fed the genetically engineered processed soya (Hammond et al, 1996). These differences plus the difference in trypsin-inhibitor identified in another paper (Padgette et al, 1996) contradict the claim that the genetically modified soya and its products "are equivalent to, and as safe for human consumption as beans from other conventional soya bean strains and products derived from them" (UK ACNFP statement, cited in "Some Important Information About Genetically Modified Soya" by Corporate Relations Department, Van den Bergh Foods Ltd, ).
6. Monsanto did not submit any data on the level of glyphosate residues in the transgenic soya bean, nor on products derived from it. The toxicity of glyphosate has been reviewed by Cox (1995). Acute toxicity of some glyphosate products include eye and skin irritation, cardiac depression and vomiting. In California, glyphosate is found to be the third most commonly-reported cause of pesticide related illness among agricultural workers. The toxicities are often associated with supposedly inert solvents and detergents in some formulations which greatly increase the toxicity of glyphosate. These synergistic interactions between chemical pollutants in our environment are now well-documented (see Howard, 1998). Chronic toxicity of glyphosate include testicular cancer and reduced sperm counts and other negative reproductive impacts in rats (FAO/WHO, 1986; Ohnesorge, 1994). There are also indications that glyphosate formulations cause mutations in genes (Kale et al, 1995).
7. The currently acceptable daily intake (ADI) of glyphosate set by the WHO, is 0.3mg/kg body weight/day, and should not exceed 10mg/kg/day. The latter is the lowest level at which glyphosate has been shown to adversely affect reproduction in rats. Glyphosate residues have already been found in strawberries, lettuce, carrots, barley and fish. These residues persisted for at least one year after the herbicide was applied (see Greenpeace Report, 1998 and references therein). Glyphosate residues are bound to increase in glyphosate resistant crops as herbicide usage increases. In anticipation of that, the 1996 EU limit for soya beans has been increased to 20mg/kg/day, while the US limit is increased to 100mg/kg/day. These are well over the threshold at which reproductive and other health impacts are evident from animal experiments.
E. Wider ecological concerns of the genetically engineered soya beans
1. Glyphosate is a broad-spectrum herbicide which will have major impacts on biodiversity (see Greenpeace Report, 1998, and references therein). It kills all plants indiscriminately. This will destroy wild plants as well as insects, birds, mammals and other animals that depend on the plants for food and shelter. In addition, Roundup (Monsanto's formulation of glyphosate) can be highly toxic to fish. Glyphosate also harms earthworms and many beneficial mycorrhizal fungi and other microorganisms that are involved in nutrient recycling in the soil. It is so generally toxic that researchers are even investigating its potential as an antimicrobial (Roberts et al, 1998).
2. Glyphosate, in being a broad spectrum herbicide as well as harmful to soil microorganisms that are crucial for natural soil fertility, is completely incompatible with organic agriculture. And that applies obviously to genetically engineered glyphosate-resistant plants that are tied to glyphosate sprays. Many studies within the past 10 to 15 years have shown that sustainable organic agriculture can improve yields and regenerate agricultural land degraded by intensive agriculture and hence offer the real solution to "feeding the world" (see Pretty, 1995; Ho, 1998a,b). Sustainable organic agriculture depends on maintaining natural soil fertility as well as on mixed cropping and crop rotation; thus reversing the destructive effects of intensive agriculture that have led to falling productivity since that 1980s. Glyphosate resistant plants will set us back from the real solution to food security (see Ho, 1998a,b). Yet it is the major category of genetically engineered crops on offer.
3. Glyphosate resistance genes can spread to nongenetically engineered crops as well as wild relatives by cross-pollination. The transgenic plants themselves as well as the hybrids can become weeds. Genetically engineered glyphosate resistant soya bean is particularly relevant for Asia and Australasia where wild relatives of soya beans exist (see Greenpeace Report, 1998).
4. Another route for glyphosate resistance genes to spread is horizontally, i.e., via infection, to soil microorganisms (see paragraph C.4). A possible scenario is that pathogens will acquire the resistance and out-compete beneficial species as glyphosate is increasingly applied. All bacteria and other microbes, some of which can cause diseases, are normally susceptible to glyphosate (Roberts et al, 1998).
5. Finally, the use of glyphosate with genetically engineered resistant plants will encourage the evolution of glyphosate resistance in weeds and other species, even without cross-pollination. A ryegrass highly resistant to glyphosate has already been found in Australia (New Scientist, 6 July, 1996). Resistance evolves extremely rapidly because all cells have the capability of mutating their genes at high rates to resistance if they are exposed continuously to sub-lethal levels of toxic substances including herbicides, pesticides and antibiotics. This is inherent to the "fluidity" of genes and genomes that has been documented within the past 15 years (see Ho, 1998a). It will render resistant plants useless after several generations, as the herbicide is widely applied. At the same time, resistant weeds and pathogens may become increasingly abundant. Additional herbicides will then have to be used to control the resistant weeds.
Addendum (October 23 1998)
A recent report (Bergelson, J., Purrington, C.B. and Wichmann, G. (1998). Promiscuity in transgenic plants. Nature 395, 25) describes the results of experiments showing that transgenes may be up to 30 times more likely to escape than the plants's own genes, probably being transferred horizontally by insects visiting the plants for pollen and nectar.
Article first published April 2000
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