New GM Toxin Looms over Our Food

ISIS Press Release 02/12/03

Prof. Joe Cummins issues advance warning of new GM toxin from soil bacterium that’s to be incorporated into our food crops.

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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