ISIS Press Release 19/03/08
Transgenic Potato Not to be Released
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 ISIS.
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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.
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.
Synthetic Repellent
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.
General considerations
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.
References
1. APPLICATION FOR CONSENT TO RELEASE GMOs (FOR PURPOSES OTHER THAN MARKETING)
UNDER THE GENETICALLY MODIFIED ORGANISMS (DELIBERATE RELEASE) REGULATIONS 2002
– HIGHER PLANTSCentre for Plant Sciences University of Leeds Control of potato
cyst-nematodes with minimised environmental impact 2008
2. Atkinson HJ, Johnston KA, Robbins M. Prima facie evidence that a phytocystatin
for transgenic plant resistance to nematodes is not a toxic risk in the human
diet. J Nutr. 2004, 134(2), :431-4.
3. Niccoli G, Conte M, Bona RD, Altamura L, Siviglia M, Dato I, Ferrante G,
Leone AM, Porto I, Burzotta F, Brugaletta S, Biasucci LM, Crea F. Cystatin C
is associated with an increased coronary atherosclerotic burden and a stable
plaque phenotype in patients with ischemic heart disease and normal glomerular
filtration rate. Atherosclerosis. 2007 Nov 3 [Epub ]
4. Lee BW, Ihm SH, Choi MG, Yoo HJ. The comparison of cystatin C and creatinine
as an accurate serum marker in the prediction of type 2 diabetic nephropathy.
Diabetes Res Clin Pract. 2007, 78(3), :428-34.
5. Djoussé L, Kurth T, Gaziano JM. Cystatin C and risk of heart failure in
the Physicians' Health Study (PHS). Am Heart J. 2008, 155(1), 82-6.
6. Sharma S, Rashid F, Bano B. Biochemical and biophysical changes induced
by fungicide sodium diethyl dithiocarbamate (SDD), in phytocystatin purified
from Phaseolus mungo (Urd): a commonly used Indian legume. J Agric Food Chem.
2005, 53(15), 6027-34
7. APPLICATION FOR CONSENT TO RELEASE GMOs (FOR PURPOSES OTHER THAN MARKETING)
UNDER THE GENETICALLY MODIFIED ORGANISMS (DELIBERATE RELEASE) REGULATIONS 2002
– HIGHER PLANTS Defra Reference number 07/R31/1 Control of potato cyst-nematodes
with minimised environmental impact Additional information requested by DEFRA
GM team 2008 regarding potato cyst-nematodes with minimised environmental impact
8. Liu B, Hibbard JK, Urwin PE, Atkinson HJ. The production of synthetic chemodisruptive
peptides in planta disrupts the establishment of cyst nematodes. Plant Biotechnol
J. 2005, 3(5) 487-96.
9. Martin RJ, Robertson AP Mode of action of levamisole and pyrantel, anthelmintic
resistance, E153 and Q57. Parasitology 2007, Pt 8, 1093-104.
10. Shapiro-Ilan1.D Entomopathogenic nematodes and insect management Encyclopedia
of Entomology 2004, 781-784 DOI 10.1007/0-306-48380-7_1430
11. Klingen I, Haukeland S The soil as a reservoir for natural enemies of
pest insects and mites with emphasis on fungi and nematodes. Progress in
Biological Control An Ecological and Societal Approach to Biological Control
Volume 2 2006 145-211 DOI 10.1007/1-4020-4401-1
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