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ISIS Report 02/12/03
New GM Toxin Looms over Our Food
Prof. Joe Cummins issues advance
warning of new GM toxin from soil bacterium that’s to be incorporated into
our food crops.
Sources
for this report are available in the ISIS members site.
Full details here
The soil bacterium, Bacillus thuringiensis (Bt), has proven to be
a rich source of toxins for killing insect pests. Most of the toxin genes now
being used in genetically modified (GM) crops are produced in sporulating Bt,
and belong to the Cry family: designated Cry1, Cry 2 etc. up to at least Cry
41. The Cry genes are further distinguished as Cry1A, Cry1B etc for substantial
sequence variations, and labeled Cry1Aa, Cry1Ab etc for very small differences
in sequence. The Cry gene toxins target specific insect cell receptor proteins
and create pores that lead to osmotic lysis of the insect gut cells. Only a few
Cry genes have found favour in GM crops. Along with the Cry genes, Cyt genes
have been characterized that are distinct from Cry genes and act by breaking
open the insect’s blood cells.
In recent years, vegetative insecticidal proteins (VIP) have been found
to have potent, broad-spectrum activity against insects. VIP genes are not
homologous to Cry and Cyt genes, and bind to cell membrane proteins different
from the other toxins.
Syngenta Corporation, producers of chemical and biological pesticides,
has patented the VIP genes for use in transgenic crop plants and microbes.
Syngenta’s United States patent 6 429 360 covers the use of Bt-VIP genes
and their synthesis and alteration to improve performance in crop plants.
Syngenta’s patent provided evidence that VIP3A toxin produced apoptotic
type of cell death, including the production of membrane-bound apoptotic bodies
and activation of endonuclease enzymes that cleave chromatin into discrete
fragments.
Apoptosis (meaning petals falling from a flower) is a form of programmed
cell death common to all cells with discrete nuclei. It is a part of normal
development, but the VIP3A toxin uses programmed cell death to destroy the
cells of the insect gut. In order to function fully in the plant cells, the
Bt-VIP3A gene is modified in its coding sequence; a strong promoter added, as
well as an intron to facilitate transfer of the pre-messenger RNA from nucleus
to cytoplasm; and the usual transcription terminator and polyA addition
sequences.
The insect VIP3A receptor was identified and its characteristic "death"
recognition sequence was characterized. Organisms whose cells have nuclei
generally have receptors with death signals and the insect VIP3A receptor is a
unique member of the class of sequences.
Syngenta has petitioned the United States Environmental protection
Agency (EPA) for commercial release of event COT102 cotton containing a
synthetic VIPA3 gene. Presumably, corn containing the VIP3A gene will be
proposed for commercial release. The EPA report of the Syngenta petition for
tolerance in or near food reported that the VIPA3 toxin was homologous to the
VIP3A toxin in numerous Bt strains. However, the petition failed to mention the
numerous change in DNA sequence including promoter, introns, terminator and
polyA signal, which were reported in the Syngenta patent for VIP genes.
Mammalian acute toxicity studies were done using the VIPA3 toxin produced in
bacteria, not the toxin produced in modified corn or cotton. The VIPA3 toxin in
cotton is assumed to be substantially equivalent to the toxin produced in
bacteria but, as in the case of most other commercial Bt cry toxins, the toxin
protein is allowed to diverge significantly from the bacterial toxin so long as
the protein remains active against insect cells and is immunologically similar
to the toxin produced in cotton. The toxin tested by Syngenta showed no overt
acute toxicity and there was no indication that it was allergenic. Sequence
analysis showed no overt similarity to known toxins. The practice of putting
forward Bt toxins produced in bacteria as equivalent to the Bt toxins produced
in crops was criticised earlier. The practice is unsound and should, at least,
be made very clear in the government announcements on the safety testing of GM
crops bearing genes for Bt toxins.
The EPA report notes: "Once in the insect gut, the VIPA3 protein binds
to specific receptors (different from those by Cry 1A proteins) and forms ion
specific pores." There was no discussion, in the EPA report of the apoptosis
and binding to death sequences receptors mentioned in the Syngenta patent.
Indeed, the claim that the VIP3A toxin had no obvious homology to mammalian
toxins seems to have ignored the homology of all apoptosis receptor death
sequences. The contrast between the Syngenta patent and the EPA report is
perplexing because the patent document was well supported with experiments
while the EPA report provided little scientific evidence for its claims.
In conclusion, the Bt toxins of the VIP gene family provide potent
broad spectrum insect control. The toxins have been reported to act by binding
to death sequences and triggering apoptosis in insect cells. At the very least,
the potential impact of such toxins on the receptors and death sequences in
mammalian cells should be fully evaluated before GM crops bearing the toxins
enter the mammalian food chain.
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