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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.
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
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.
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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