Prof. Joe Cummins
A version of this article was submitted to Advisory Committee on Releases to the Environment (ACRE) 4 March 2008 on behalf of I-SIS.
The University of Leeds Centre for Plant Sciences submitted an application to release genetically modified (GM) potatoes to the open environment for a field trial [1]. The transgenic potato plants have been produced using Agrobacterium tumefaciens. All constructs have the selectable marker gene for neomycin required only for selection of transgenic lines for evaluation and according to the application, “known to be biosafe as used.” The potato will express a cysteine proteinase inhibitor (cystatin) from rice and/or a repellent of synthetic origin. Both confer resistance to potato cyst-nematodes. Cystatins limit growth of the nematode while the repellent prevents the nematodes from entering the roots of the potato. Their expression will be under the control of CaMV35S promoter from Cauliflower mosaic virus for constitutive expression, or promoters that restrict expression to roots. The root specific promoters used are from a serine threonine kinase (ARSK1) and the MDK420 gene of Arabidopsis thaliana; they provide expression in roots and at root tips respectively. A signal sequence from the Calreticulin gene of Nicotiana plumbaginifoli are used in lines expressing the repellent to favour its release from root. The nos terminator sequence from Agrobacterium tumefaciens terminates transcription of gene sequences. Six strains of GM potatoes are to be tested: constitutive cysatin, root specific cystatin, root tip repellent, constitutive repellent, root tip repellent plus root tip specific cystatin. and constitutive repellent plus root specific cystatin.
The cystatin modified potatoes have been studied extensively according to the application for consent [1]. The safety of the protease inhibitor in transgenic potato in the human diet was evaluated in a small rat feeding study [2]. The inhibitor caused a small but significant decrease in the weight of the animals’ liver, but there were few other detectable impacts at the levels of inhibitor studied.
The application for consent failed to mention that that there have been numerous studies published in the medical literature showing that risk of heart failure, atherosclerosis and nephropathy were marked by elevated cystatin blood levels [3-5]. It is presently unclear whether or not elevated cystatin causes kidney damage, or whether it results from kidney pathology of another origin. At any rate, it is unwise to ignore evidence showing that greatly elevating the plant source of cystatin could be harmful to humans.
Cystatin has been found damaged and reduced in activity upon exposure to a common fungicide sodium diethyl dithiocarbamate (Mancozeb) [6]. Carbamate pesticides are used extensively, which may negate the effectiveness of the modified potato’s defence against nematodes.
The gene and the peptide that it produces are not fully or well described in the consent application [1]. Additional information was provided [7], which clarified some of the properties of the repellent. However, neither document gave a clear description of the repellent synthetic peptide and its synthetic gene. Little actual information was provided on the organization of the gene and the messenger RNA and the processing of the peptide in the potato cell. Such information is necessary. The mode of action of the synthetic peptide was also not clearly stated in the original application and a brief description was given in additional information [7].
A publication from the Leeds group described producing a peptide in potato to disrupt cyst nematodes, and compared the mode of action of the peptide to an acetylcholinesterase inhibitor aldicarb [8]. Aldicarb is a toxic pesticide slated for withdrawal from EU. However, the additional information document [7] compared the synthetic peptide in the application to the anthelminic levamisole, an inhibitor of the nicotinic acetylcholinesterase receptor [9]. The synthetic peptide excreted from the potato root paralyses the nematode preventing it from invading the potato. Both of the documents of the application for consent [1,7] measure the peptide in plant and soil by its ability to inhibit an enzyme. However, the loss in ability to inhibit an enzyme does not necessarily mean that the remains of the peptide are not toxic to mammals. Some study of the toxicity of the breakdown products of the synthetic peptide should have been done because such products may pollute ground water. The synthetic peptide and its breakdown products should have should have been studied fuller to determine whether or not they are toxic to mammals.
The application for consent included a discussion justifying the use of the antibiotic neomycin resistance marker in the proposed open field releases even though the antibiotic is still used in medicine [1]. It stated that as the marker was used in food crops released commercially in the North and South America it must be safe. Such reasoning is unsound.
The application for consent seems to have overlooked the important question regarding the potential impact of the modified potatoes on beneficial nematodes that control many insect pests described in two major reviews [10, 11]. The elimination of a natural population of such nematodes from the test site would increase the need for extensive insecticide spraying. It would be wise to carry out an inventory of these nematodes on the test site prior to commencing the actual experiments, and to determine from the experiment whether the loss of beneficial nematodes and the added cost of controlling insect pests exceed the benefits of decreasing the nematode pests.
In conclusion, Consent should not be considered until the potential toxicity (including immunogenicity) of the repellent and repellent breakdown products are fully investigated and reported, and taken into account.
Article first published 19/03/08
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