(Thanks to the Society for the Promotion of Nutritional Therapy, for the reproduction of the following article. Thanks to Dr. Ron Epstein for sending us this article for the MEC Newsletter.)
Genetic engineering has already made a significant impact in the manufacture of foods and food supplements. Enzymes derived from genetically engineered bacteria, yeast or fungi are now routinely used to increase efficiency in a number of processes. Pectin degrading enzymes increase both the yield and the clarity of tinned fruit and fruit juices. Amylases are used in bread making to ensure better rising of the dough. Rennet which is used in the production of cheese was traditionally obtained from the calf stomach. Nowadays virtually all cheese is made from rennet derived from yeast or bacteria engineered to produce this calf enzyme more cheaply and in essentially limitless quantities. Earlier this year in the UK, approval was granted for the manufacture and marketing of riboflavin from genetically engineered bacteria. The list of agricultural applications of this technology are even more extensive and impressive and will therefore be the main focus of this article.
Genetic engineering is said to promise among other things, disease resistant crops and animals, tastier food with improved nutritional value, crops that produce their own pesticide and which are herbicide resistant and crops which can grow in "marginal" soil and climatic conditions with higher yields to feed the world's ever expanding population. Arguably the greatest claim of those who endorse the use of genetic engineering in agriculture, is that it is safe, more precise and a natural extension of traditional cross breeding methods for generating novel varieties of crops and farm animals. It is said that this new technology simply gives nature a helping hand with something that would happen anyway. There is no doubting the power of genetic engineering to produce more rapidly new varieties of crops and farm animals. However, since technically speaking traditional methods and genetic engineering bear little resemblance to each other, how valid are these claims? Is it as precise and safe as it is made out to be? If there are inherent dangers with this technology, should we be using it in industrial processes and agriculture since there are safer alternatives to producing the same products as well as new varieties of crops and animals?
Genetics and Genetic Engineering
In order to answer these questions we need to be familiar with some of the basic principles of genetics and genetic engineering. Genes are discrete units of DNA. They are the blueprints which carry the information for the proteins which in turn make up all the structures and functions (biochemistry) that constitute the body of any organism from bacteria to humans. Gene function is extremely tightly controlled so that the right proteins are made in the correct place within the organism, at the right time in it's life and in the appropriate quantity. This ensures an integrated and balanced functioning of all the tens of thousands of structures and processes that make up the body of any complex organism be it plant or animal. One will not normally find liver functions in the brain or leaf specific proteins in the fruit and vice versa!
Nature has also evolved mechanisms whereby cross breeding can only take place between very closely related species. With traditional breeding methods, different variations of the same genes in their natural context are exchanged. This preserves tight genetic control and functions that are vital for health and the integrity of life as a whole. In marked contrast, genetic engineering allows the isolation, cutting, joining and transfer of single or multiple genes between totally unrelated organisms circumventing natural species barriers. As a result combinations of genes are produced that would never occur naturally.
Genetically engineered (transgenic) crops containing genes from viruses, bacteria, animals as well as from unrelated plants have been generated. Furthermore, the newly introduced gene units are composed of artificial combinations of genetic material. For example, transgenic tomatoes and strawberries are under development which contain the "anti-freeze" gene from an arctic fish. In addition, parts of a plant virus are used to allow this fish gene to "switch on" in it's new host. All this in turn coupled to an antibiotic resistance "marker" gene. It is hoped this combination will allow greater tolerance to frost. This is clearly a great technological advance. However, the manipulation and transfer of DNA from one organism to another by genetic engineering can only be carried out with any degree of precision in lower forms of life such as bacteria and yeast although, as we shall see, complications may arise even in these cases. The generation of transgenic plants and animals is currently an imperfect technique.
Once injected into the reproductive cells of an organism, the introduced gene randomly incorporates itself into the DNA of it's new plant or animal host. This always results in a disruption, to a lesser degree, of the tight genetic control and balanced functioning which is retained through conventional cross breeding. In addition, it is assumed that the introduced gene will behave in exactly the same way in it's new host as it does in it's native environment which frequently will not be the case. These effects combine to always produce a totally unpredictable disturbance in host genetic function as well as in that of the introduced gene. Therefore from the standpoint of the fundamental principles of genetics and the limitations in the technology, genetic engineering is neither more precise nor a natural extension of traditional cross breeding methods. If anything the opposite would appear to be true.
Potential Health Hazards
Does the molecular imprecision of genetic engineering matter if quality of life can be improved without safety or value of the food being compromised? Unfortunately, disruptions in the biochemistry of the transgenic organism have already been observed to produce a number of unexpected outcomes whose unpredictability is the greatest worry. A tomato, for example has been engineered to have a longer shelf-life but unexpectedly also bruises more easily which resulted in major problems during it's harvesting. Furthermore, this tomato may still look good after 6-8 weeks but is lacking in flavour and has reduced nutritional value. Will the outcome be the same with the many other ripen-on-demand or longer-shelf-life fruits and vegetables about to be launched?
The production of novel toxins and allergens poses the most immediate potential health risk. In 1989 an epidemic of a new disease hit the USA. Called eosinophilia myalgia syndrome (EMS) it was eventually traced, after several months, to the consumption of a particular brand of tryptophan food supplement derived from bacteria genetically engineered to overproduce this amino acid. The engineering process had unexpectedly produced metabolic perturbations resulting in the formation of a novel toxin from the excessive amounts of tryptophan present within this organism and which contaminated the final product. Out of the estimated 5000 people who contracted EMS, 37 died and 1500 are permanently disabled with sickness. Therefore, even in simple cases such as bacteria where genetically engineered modifications can be carried out with some precision, unpredictable disturbances in biochemical functioning with disastrous outcomes can occur.
It is therefore not surprising to find that unexpected toxins and ill effects to the host have now been documented in the more complex genetically engineered organisms such as yeast, plants and animals. The only other recorded case of ill health in humans resulting from a genetically engineered food is from soya containing a brazil nut protein which, during pre-marketing tests, still gave rise to reactions in individuals allergic to brazil nuts. Although overt health problems are potentially rare, it is their unpredictability which causes the greatest concern. Therefore, the lessons learnt from these incidents serve as a timely reminder as hundreds of foods derived from genetically engineered crops or produced using genetically engineered components are poised for commercialism over the next few years. Generally, these findings highlight the fact that there are always potential hidden dangers when artificially manipulating on this finest level of life.
Environmental Impact And Biodiversity
The long term environmental impact of transgenic crops and animals is still far from clear. Transgenic salmon containing genes from the arctic sea flounder which grow six times larger and ten times faster are currently being farmed in Canada and Scotland. Since 20% losses during storms is the accepted norm on fish farms, this "super salmon" will inevitably escape into the wild with unknown ecological consequences. The potential problems with engineered micro-organisms and plants are even greater. There are a number of ways in which genetically engineered modifications can inadvertently be spread in the environment. Firstly, transgenic crops can simply cross pollinate with related wild varieties. Secondly, many species of micro-organisms are naturally adapted to pick up on new genetic material through a number of different mechanisms which can result in the very rapid spread of engineered traits including antibiotic resistance.
Plant viruses have also been demonstrated to readily incorporate into their own genetic make up engineered genes in transgenic plants. This can not only result in the rapid spread of engineered properties to other plants but also the creation of new strains of disease causing viruses with an altered host range. It is therefore particularly disconcerting to find that an engineered insect virus possessing the scorpion toxin gene is currently under trials in Canada for spraying on crops as a broad spectrum pesticide. Most transgenic crops that have been produced or are under development, are engineered to be resistant to herbicides or to generate their own pesticide.
Field trials in Scotland and Denmark using transgenic, herbicide resistant oilseed rape, have already demonstrated efficient cross pollination with related, normally weedy wild brassica varieties within a single growing season generating herbicide resistant "superweeds". Similar findings have been recorded with potatoes. Transgenic cotton containing the Bt bacterial pesticide gene grown in the southern USA this year, still resulted in millions of dollars in losses to the farmers from bollworms. Experiments have shown that the continued presence of a pesticide on plants, as is the case with genetically engineered varieties, results in the more rapid appearance and maintenance of highly tolerant pests which may even have contributed to the cotton disaster.
A number of crops are also being generated for growth characteristics such as wheat that can fix it's own nitrogen and therefore require less artificial fertiliser, or rice that can grow in marginal salty waters. The spreading of these properties to relatives through cross pollination can result in immeasurable ecological disturbances as wild plants are displaced by these more hardy varieties possessing engineered traits. Transgenic crops would therefore appear to have a built in obsolescence. They may lead to reduced use of herbicides, pesticides and artificial fertilisers in the short term but an even greater dependence on agrochemicals in the longer term as resistant weeds and insects rapidly appear in addition to other ecological disturbances. This clearly results in higher costs to the farmer and consumer as well as an increase in environmental pollution.
The use of genetic engineering threatens to compound an already existing problem, namely the reduction in biodiversity of food crops. The global dissemination of select hybrids for cereals and pulses produced by seed companies in the more industrially developed nations of the world, has already replaced most traditional varieties. Earlier this century there were more than 100,000 varieties of rice grown in the world, each one ideally adapted to the local conditions where it was propagated. The "green revolution" has now reduced this to only 10-15,000 varieties. In addition, a recent report by the National Research Council (NRC, Washington DC, USA) focused on how indigenous crops in Africa such as fonio, pearl millet and African rice have been discarded as inferior in favour of Asian rice and European and American imports of maize and wheat.
The wide scale introduction of a few genetically engineered types will reduce this crop biodiversity still further. This could have catastrophic consequences on world food supply if, for example, an engineered pest resistant crop was to be destroyed by the rapid appearance of tolerant insects. It was a lack of crop diversity that resulted in the Irish potato famine 150 years ago! Furthermore, it turns out that the indigenous African grains are far from inferior and are not only nutritious but also well adapted to the harsher growing conditions experienced in many parts of this continent. It would therefore appear to be far more sensible to adopt the NRC's suggestion of developing these natural varieties to feed Africa's burgeoning population rather than waste effort producing genetically engineered wheat, maize or rice to withstand climatic and geographical conditions which they cannot tolerate.
Current Safety Regulations: General Toxicity Testing Required
There are three advisory committees established by the government which are responsible for assessing the risks to health and the environment of genetically engineered organisms (GMOs) and food products in general. All three report to the Department of the Environment and the Ministry of Agriculture Fisheries and Food. The release of GMO's, be it bacteria, viruses, plants or animals, must be approved by the Advisory Committee on Releases to the Environment (ACRE) who must be satisfied that no great danger is posed by it's release. The safety of genetically engineered food and food products produced using genetically engineered components and processes, is assessed by the Advisory Committee on Novel Foods and Processes (ACNFP). If a product receives safety clearance by the ACNFP, it is then referred to the Food Advisory Committee which makes recommendations on matters regarding the labelling, composition and chemical safety of these food products. With regard to health risks, the ACNFP demands a very strict assessment of the levels of known toxins and allergens.
Unfortunately, there is no requirement for general toxicity testing akin to that used for pharmaceuticals. This may lead to unexpected, unknown toxins or novel allergens being discovered only if a health problem arises. Furthermore, food processing which either destroys or removes the genetic material and it's protein product is assumed as being safe. Nevertheless, toxins and allergens may be present in the final product. Interestingly, the tryptophan food supplement disaster already discussed would occur even under these current rulings due to the fact that it was caused by an unexpected, new toxic contaminant present in the final, presumed pure product devoid of DNA and proteinaceous material. It therefore would require neither toxicity testing nor, as we shall see, labelling. Full Disclosure Labelling Required
At present, only products which are, or contain "live" GMOs (e.g. salad vegetables, fruits, yoghurt), those deemed to be nutritionally "substantially different" from the parental, non-engineered organism and those which contain genetic material from human or animal sources which may be objectionable on religious or ethical grounds, need be labelled. Genetically engineered modifications for "enhanced agricultural performance" (e.g. herbicide and pest resistance), and processed food products derived from GMOs (e.g. oil from soya beans or oilseed rape), those which have used GMOs as part of their production (e.g. yeast in bread baking) or use products derived from GMOs (e.g., enzymes from bacteria in fruit juice production; calf rennet from yeast in cheese making; need not be labelled.
Food processing which destroys or removes the genetic material and the proteins derived from it is assumed to be safe and does not require labelling. Fortunately for those who have reservations about engineered food, earlier this year the Codex Alimentarius Committee on Food Labelling which sets international standards, ruled that genetically engineered food could not be labelled as "organic" even if grown under organic husbandry conditions. It is clear that under this current UK and soon to be introduced EU legislation, very few genetically engineered foods are required to be labelled. In the vast majority of cases it is being left to food producers and retailers as to whether a product should be labelled or not. Most major retailers have stated that they will label all such products although some discrepancies have already emerged. Only the Co-op supermarket outlet labels it's cheese as being derived from genetically engineered rennet.
No tinned fruit or fruit juice is labelled as using enzymes from engineered micro-organisms as part of it's manufacture. The greatest concern is that the producers of commodity products such as cereals, grain, pulses and oilseed rape are not in favour of labelling and therefore not prepared to segregate engineered from natural varieties. This in turn makes it very difficult for food processors and retailers to know what is or is not engineered and to know what to label accordingly. This includes the engineered herbicide resistant soya beans and pest resistant maize harvested this autumn in the USA and the herbicide/pest resistant oilseed rape in Europe. Products from these crops are extensively used in the food processing industry. Soya bean ingredients (flour, protein, oil, lecithin) are added to 60% of all processed foods whereas components derived from maize (flour, starch, corn syrup) are included in approx. 50% of processed foods. Rape seed oil is inexpensive and widely used.
Therefore, unless legislation is passed to ensure segregation, it will be virtually impossible to avoid genetically engineered components in our food even in the very near future. Arguments concerning the impracticality of segregation are untenable in the face of public announcements by wholesalers and exporters in the USA that they are quite happy to provide segregated soya beans if there was sufficient demand. In addition, simple and extremely sensitive tests are being offered by a US company to check batches of grain and pulses for the presence of genetically engineered varieties.
A full disclosure labelling of genetically engineered food is required for two reasons. Firstly, labelling will protect the consumer's democratic right to know what they are eating and allow them to make an informed choice as to whether to buy these products. Secondly, without labelling it would be difficult if not almost impossible to trace any health problems that may arise given the diversity of people's diets. The source of the contaminated tryptophan which caused the EMS tragedy took several months to trace since the product was not labelled as being derived from a genetically engineered bacterium. Also, even the presence of small amounts of an allergen in a food product can cause a severe reaction in a sensitive individual who clearly needs to avoid it.
Conclusions And Future Developments
Generating new crop hybrids for higher yields has been the dominating factor in modern agriculture for many years. However, quantity has come in many cases at the expense of quality. High yielding varieties can not only be deficient in flavour but also in nutritional value. It is perhaps ironic that food producers are now relying on genetic engineering to put the "taste" back into food rather than returning to more traditional varieties. When analysed from the viewpoint of the fundamental principles of molecular genetics, it is evident that the generation of genetically engineered plants and animals is an imprecise technology with inherent potential dangers. Foods derived using this technology can therefore quite justifiably still be called "experimental" especially in the absence of data testing for the unexpected production of novel toxins and allergens.
Clearly, biotechnologists should not forget the basic principles of genetic functioning or the limitations of the technology as it stands whilst trying to meet their technical and commercial objectives. There is sufficient evidence to show that things can still go drastically wrong. Furthermore in the absence of full mandatory labelling of engineered foods, the public would appear to unwittingly be participating in a vast global food experiment whose outcomes are far from certain. Although very few genetically engineered crops are currently approved or already marketed, if current trends go unabated within the next 5-8 years most food plants of the world will be modified by this technology. This includes not only major commodity items (cereals and pulses) but also common fruits and vegetables including apples, strawberries, cantaloupe melons, grapes, sugar beets and potatoes to name but a few.
Those who do not want to participate, at least for the time being , in the "experiment", will find it increasingly difficult to avoid engineered foods. Given the ruling of the Codex committee, eating only organically grown food would appear to be the easiest way of avoiding them. The engineered soya beans and maize are due to arrive in Europe from the USA this November [they are of course already here as this was written last year] and will find their way, as discussed, into 60% of processed foods. A boycotting of these processed foods, unless reassurances can be given about the origin or variety of their soya and/or maize, would appear to be the only course of action open to the concerned individual. Last but not least we must also remember that unlike chemical pollutants and other problems in the food chain such as a BSE epidemic, once genetic pollution causing toxins/allergens and ecological disturbances is in our soil, crops, animals and their wild relatives, it cannot be cleaned up or simply allowed to decay and will be passed on to all future generations indefinitely. Given that we have viable and safer alternatives, is it worth taking the risk?
Toxin and Allergic Effects
Eosinophilia-myalgia syndrome and trytophan production: a cautionary tale. Mayeno AN and Gleich GL (1994) Trends in Biotechnology 12: 346-352.
Enhanced accumulation of toxic compounds in yeast cells having high glycolytic activity: a case study on the safety of genetically engineered yeast. Inose T and Kousaku M (1995) International Journal Food Science Technology 30: 141-146.
Identification of brazil-nut allergen in transgenic soybeans. Nordlee JA, Taylor SL, Townsend JA, Thomas LA and Bush RK (1996) The New England Journal of Medicine 334: 688-692.
Allergies in Transgenic foods-questions of policy. Nestle M (1996) The New England Journal of Medicine 334: 726 727.
Allergenicity assessment of foods derived from genetically modified plants. Fuchs RL and Astwood JD Food Technology February 1996: 83-88.
Ill effects in Plants Caused by Transgenes
Manipulation of flower structure in transgenic tobacco. Mandel, MA et. al. (1992) Cell 71: 133-143.
Forcing expression of a soybean root glutamine synthetase gene in tobacco leaves induces a native gene encoding cytosolic enzyme. Hirel, B., Marsolier, MC., Hoarav, A., Hoarav, J., Brangeon, J., Shafer, R. and Verma, D.P.S. (1992) Plant Molecular Biology 20:207-218.
Environmental Hazards
Transgenic plants on trial. Kareiva, P. (1993) Nature 363: 580-581.
Ecology of transgenic oilseed rape in natural habitats. Crawley MJ et al. (1993) Nature 363: 620-623.
Gene dispersal from transgenic potatoes to conspecifics: a field trial. Skogsmyr, I. (1994) Theoretical and Applied Genetics 88: 770-774.
The risk of crop transgene spread. Mikkelsen, T.R., Andersen, B. and Jorgensen, R.B. (1996) Nature 380: 31.
Inheritance and stability of resistance to Bacillus thuringiensis formulations in diamond back moth, Plutella Xylostella (Linnaeus) (Lepidoptera: Yponomeutidae). Hama, H., Suzuki, K. and Tanaka, H. (1992) Applied Entomology and Zoology 27: 355-362.
Complementation of coat-protein defective TMV mutants in transgenic tobacco plants expressing TMV coat protein. Osbourn, J.K., Sarkar, S. and Wilson, M.A. (1990) Virology 179: 921-925.
Recombination between viral RNA and transgenic plant transcripts. Greene, A.E. and Allison, R.F. (1994) Science 263: 1423-1425.
Bt cotton infestations renew resistance concerns. Fox, J.L. (1996) Nature Biotechnology 14: 1070.
Human Genes into Plants
A mammalian 2-5A system functions as an antiviral pathway in transgenic plants. Mitra, A. et. al (1996) Proc. Natl. Acad. Sci. USA 93: 6780-6785.
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Copyright Mendocino Environmental Center 1997
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