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ISIS Report 06/12/06

Universal Condemnation Meets UK Government’s Green Light for GM Potato Trials

Assumptions of safety not justified by existing evidence

The government must withdraw permission for the trials, or the regulators should be held responsible for any harm caused. Dr. Mae-Wan Ho and Prof. Joe Cummins

A fully referenced version of this paper is posted on ISIS members’ website. Details here.

Big food companies reject GM potatoes and oppose the trials

The UK government has given permission to German biotech company BASF Plant Science GmbH for the first trials of a genetically modified (GM) crop in the country since 2003 [1]. BASF’s GM blight-resistant potato was granted permit for field trials in Ireland earlier this year, but the company abandoned its plans in face of strong opposition from civil society organisations and strict conditions imposed by Ireland’s Environmental Protection Agency [2].

The big food companies in the United States, including McDonalds, McCains, Burger King and Pringles, had rejected GM potatoes in 2002; and in August 2006, when BASF applied for a UK trial permit, the British Retail Consortium said UK supermarkets would not be stocking GM potato [3].

The British Potato Council has also made its strong opposition known the day after the government’s decision was announced [4]. It refused to endorse the trials, and said it was paramount that public concerns were addressed, and fears about possible cross-contamination allayed, before trials began. The trials are to consist of five-acre plots in Derbyshire and Cambridgeshire for five years beginning 2007, under the conditions that the plots must be left fallow after the five-year trial so any remaining tubers can be destroyed and none of the potatoes harvested enters the food chain.

The GM potatoes are modified with genes from a wild Mexican relative of potato, Solanum bulbocastanum, intended to make them resistant to the fungus causing late blight disease; but they also have marker traits, including herbicide resistance. BASF has not done environmental or health impact studies on the GM potatoes [5]. In view of the growing list of damning evidence against the safety of GM crops [6, 7] (GM Soya Fed Rats: Stunted, Dead, or Sterile; Making the World GM-Free & Sustainable ), approving the release of these GM potatoes is to subject the public to serious health risks with potentially harmful effects on wildlife.  We already know that debilitating immune reactions can be triggered by exposure to the transgenic plant, even in the case of a single gene transfer from bean to pea, a closely related species [8, 9] (Transgenic Pea that Made Mice Ill, SiS 29).

Late blight resistance is complex and the fungus versatile

Late blight is one of the most devastating plant diseases. It is caused by the fungus, Phytophora infestans, a pathogen of potato and to a lesser degree tomato. There are many genes involved in blight resistance in potato: four main dominant genes, R1 to R4, and another seven genes, five of which are alleles (alternative forms at the same site) of the complex R3 locus.

Hybridisation with wild Mexican species began in 1909, and continues to the present day. But in spite of constant efforts to create resistance, the fungus rapidly developed strains that overcame the genetic resistance. Chemical fungicides have been developed to control blight but these too failed to counter the versatility of the fungus. The fungus has two mating types (A1 and A2) both of which first appeared in Mexico. Only the A1 mating type was present in European potatoes until 1978 when the A2 mating type appeared in Britain. The presence of the two mating types greatly enhances gene exchange, accelerating the loss of genetic resistance and fungicide control [10, 11].

Technology in a hurry

In the early days, resistant potatoes were obtained using true sexual hybridisation with wild Mexican species but the resistant strains soon succumbed to mutants of the blight fungus. A wild Mexican species, Solanum bulbocastanum, was stably resistant to blight but could not be sexually crossed with potatoes.  A laboratory procedure of somatic hybridisation was used to create sexual hybrids; it involves fusing cells from cell cultures of Solanum bulbocastanum and potato, the fused cells containing nuclei of both species. When the fused cells undergo cell division, the chromosomes of the two species become mixed and a single hybrid nucleus is formed in the cells. The cells can be cultured on solid media to form a callous  (tumour) which when treated with plant growth hormones, produces plantlets that flower. The somatic hybrids have irregular meiosis (cell division in forming germ cells during reproduction, which reduces the chromosome number to half), with irregular chromosome pairing and separation, but relatively stable blight resistant lines can be obtained  [12-14]. Apart from the 11 potato blight resistance genes mentioned earlier, additional genes are involved in producing broad-spectrum resistance against blight, these include the gene RB [15], Rpi-blb1 [16] and Rpi-blb 2 [17] which are active in both potato and tomato.  Somatic hybrids are useful in identifying resistance genes and in transmitting the genes into potato breeding lines by crossing. Nevertheless, genetic modification of potato breeding lines is presently preferred, because resistance can be introduced into commercial lines with greater speed.

No studies done on species-specific processing of transgenic proteins to rule out immunogenicity or toxicity

The BASF GM potato trials [18-21] involve two broad-spectrum resistance genes, Rpi-blb1 and Rpi-blb2. These two genes code for proteins that have a nucleotide-binding site consisting of leucine-rich repeats (NBS-LRR) typical of a class of regulatory proteins. Many disease resistance genes code for proteins of that class. Numerous NBS-LRR genes are present in the typical plant genome, each protein specific for a particular pathogen, signalling a defence response that frequently involves a localized cell death (hypersensitive response) [22-24]. The blight fungus suppresses the potato defence genes in sensitive plants, but is thwarted by successful defence genes in resistant plants. The NBS-LRR resistance genes in plants are localized in the cell cytoplasm and do not span the cell membrane but are activated by signals from pathogens that penetrate into the cell [23, 24]. The cell dies and traps the invading pathogens. Plant NBS-LRR proteins generally produce antibodies when injected into mammals, but the species-specific processing of the disease resistance proteins, which contribute to the immune response, has yet to be investigated.

Denial of horizontal gene transfer based on a single research paper exposed to be fundamentally flawed

The BASF proposals [18-21] indicate that the potatoes were transformed using two plasmids, each with single copies of the two S. bulbocastanum resistance genes Rpi-blb1 and Rpi-blb2. The two genes were each regulated by its own endogenous promoter (including an intron as an enhancer) and terminator.  The plasmids also contained a mutant acetohydroxy acid synthetase (ahas) gene from the tiny mustard plant Arabidopsis that conferred resistance to the herbicides of the imidazolines group, which is approved for use in the UK for some crops, but does not appear to be approved for use with field potato [25]. The ahas gene is controlled by the nopaline synthase promoter and terminator from Agrobacterium.  The transformed potatoes are herbicide tolerant, but the herbicide is only used during selection of transformed potato cells, and not during cultivation of the potato.

Nevertheless, the herbicide tolerant gene is present in the GM potato and can be transferred, along with the other transgenes, by cross-pollination, or via horizontal gene transfer to unrelated species, especially if the GM potato is genetically unstable, as it may be, as the GM inserts of all commercially approved lines were found to have rearranged since characterized by the companies [26, 27] (Transgenic Lines Proven Unstable, SiS 20 Unstable Transgenic Lines Illegal, SiS 21). All GM lines intended for the release contain one or two copies of the plasmid inserts, but no molecular genetic details on the inserts were provided, nor evidence of genetic stability beyond the bald statement that [19], “The inserts have been found stable when shoots are propagated via cuttings. Therefore the inserts are considered to be stably integrated into the nuclear plant genome.”

BASF dismisses horizontal gene transfer [19] citing an outdated single reference [28] that one of us has exposed to be fundamentally flawed [29] (Horizontal Gene Transfer – The Hidden Hazards of Genetic Engineering). Despite the misleading title of the publication [28] that horizontal gene transfer from the transgenic potato “occurs, if at all, at an extremely low-frequency”, the actual results showed the opposite was the case. A high transfer frequency of 5.8 x 10-2 per recipient bacterium was demonstrated under optimum conditions. But the authors then proceeded to calculate an extremely low theoretical gene transfer frequency of 2.0 x 10-17 under extrapolated “natural conditions”, assuming that different factors acted independently. The natural conditions, however, were largely unknown and unpredictable, and even by the authors’ own admission, synergistic effects could not be ruled out. There is abundant direct and indirect evidence for horizontal gene transfer reviewed in many ISIS publications (see recent summary in Living with the Fluid Genome [30]).

No investigations on immunogenicity or toxicity

The expression of the modifying genes was not studied under extreme conditions of stress such as drought, water logging, heat, cold, nitrogen excess or starvation in glasshouse experiments. As in the past, GM crops have been tested under optimum conditions for growth prior to commercial or test release into the environment, where stress conditions may lead to unexpected toxicity (as well as genetic instability) in GM crops, of which a number of recent cases have emerged [7].

The BASF proposals [18-21] claim that the resistance genes are not expected to exert any toxic, allergenic or harmful effects on human health arising for genetic modification, but no feeding trials have been carried out. The genetic modifications are assumed to be safe because plants contain numerous NBS-LRR proteins, and cultivated potatoes contain R genes from the wild species S. demissum. The assumptions of safety are specious.  The S. demissum genes in commercial potatoes are NBS-LRR genes, but are not the broad-spectrum NBS-LRR genes used in the BASF potatoes. Above all, the finding that gene transfer between related species may nevertheless lead to proteins with powerful immune responses [8, 9] need to be taken on board.  The current procedure used to scan amino acid sequences of proteins for epitopes (motifs) that elicit allergic responses (involving IgE) would overlook the powerful immune responses resulting from carbohydrate chains added during processing of the proteins. The GM potatoes must be tested not only for allergenicity, but also for inflammatory and other immune responses, and proven safe before being released into the environment. Otherwise, the impacts on humans, livestock and wildlife could be devastating.

Assumptions of safety not justified on existing evidence

BASF had petitioned for field test release of the GM potatoes beginning 2005 in the Netherlands. The notice of petition indicated that the GM potato would be released in Germany, United Kingdom and Sweden but full reports of the tests were not provided [31]. In the United States, there have been five field tests with the GM potatoes in Minnesota and Wisconsin, carried out by USDA or the University of Minnesota [32]. The isolation and deployment of the RB genes in potato has been described [33, 34].

Field-testing of broad-spectrum NBS-LRR genes has begun with the potato blight resistant strains. Broad-spectrum pest-resistant strains of rice, maize, soybean, and numerous food crops will soon follow.  It is imperative that the safety of these genetic modifications to health and the environment be fully evaluated before the GM crops are released in field trials. The proposition that the NBS-LRR family of plant pest resistance genes and their products are safe for humans and for the environmental because they are found in food crops and hence require no further testing is simply not justified on the basis of existing evidence.

The UK government must withdraw permission for the trials, or else the regulators should be held responsible for any harm caused.


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