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[SANET-MG] Testing for the safety of GM crops is presently not sound science

December 9, 2004

Prof. Joe Cummins

“Testing bacterial surrogate products in place of the transgenic
products in genetically modified crops is an unsound practice”

The public relations machinery dealing with the release of genetically
modified (GM) crops idea that such modified crops have been tested and
evaluated fully. However, those crops have not been tested adequately.
The GM crops presently marketed contain synthetic approximations of
bacterial genes that have been drastically altered to enhance
productivity in the plant cell (bacterial genes are not adequately
active in plant cells). It is claimed that testing the modified proteins
from the crop is excessively expensive because isolation of the protein
from the crop is more difficult than isolating the modified protein from
bacterial surrogates grown in liquid media. Since the plant modified
genes are not adequately active in bacteria the original unaltered
bacterial genes are used to produce the proteins used in safety testing
for human and environmental impact. In most instances the modified
proteins produced in crops are not tested but instead their bacterial
surrogates are substituted in the tests. As pointed out earlier, the use
of surrogates is regulation by deceit(1). In most instances the
information that the GM crops contain untested synthetic approximations
of bacterial genes which have been tested using bacterial surrogate
products is buried in regulatory documents and patents.

However, recently investigators from Dow AgroScience published a study
comparing the Cry toxin proteins produced in transgenic corn with the
cry toxin protein produced in the bacterial surrogate used in safety
testing. The transgenic corn was modified with an altered synthetic
genes for Bacillus thuringiensis (Bt) Cry34Ab1 and Cry35Ab1 toxin genes.
The bacterial surrogate producing the unaltered toxin toxin was
Psuedomonas fluorescens. In the reported study the toxin proteins were
studied to determine whether or not the crop product and surrogate
product were substantially equivalent. The toxin proteins were
comparable in size based on gel electrophoresis, they were reactive to
similar antibodies, had similar N termini and lacked glycosylation.
Based on those data it was proposed that the transgenic toxin from maize
was substantially equivalent to the toxin produced in the bacterial
surrogate. There were a number of differences in the amino acids in the
corn product and the bacterial product but those differences were
claimed to be negligible because they are near the C terminus of the
toxin protein(2). There were as well differences in the N terminal
sequences. Comparable biological activity was reported in the
publication but as a reference to a US EPA report that did not appear to
be available on line (2). The publication shows that crude criteria were
being employed to establish that the toxin from the surrogate was
substantially equivalent to the toxin produced in the maize plant. It
seem unsound science to proceed with commercial production using an
untested toxin whose surrogate for safety testing differs significantly
from the real thing.

The synthetic genes employed in the crop plants produce proteins that
are somewhat different from the protein produced in the bacterial
surrogate, but, the codon adjustments to make the bacterial gene highly
active in the plant cell is substantial. The petition to the United
States EPA to establish a tolerance to the transgenic toxin in food
notes that the Cry toxin genes are synthetic and altered for production
in plants (3). Most of the three letter code words have to be adjusted
in the third position of the code word. In these instances the code word
change dose not alter the amino acid inserted in the protein(certain
codons are preferred in bacteria others in plants). The final synthetic
gene has a substantially altered genetic code but produces a protein
similar to the original natural gene (4,5). One might think, that since
a large number of code words can be altered in the third position
without changing the amino acid in the protein coded, a lot of mutations
could accumulate in the codons without altering the protein coded by a
gene. In fact, that accumulation of mutations has not been observed,
probably because a system of gene matching and correction called gene
conversion enforces uniformity associated with optimum gene activity.

Even though an effort has been made to study the protein products of the
synthetic genes no effort has been made to look into the activities of
the synthetic DNA itself. The synthetic genes never experienced the
forces of evolution and for that reason may exert untoward effects on
those consuming the plants containing synthetic genes. DNA itself may
trigger important metabolic responses independently of its production of
RNA and protein. For example, bacterial DNA or oligonucleotides derived
from its breakdown are important regulators of the innate immune system.
Bacterial DNA or oligonuclleotides have higher levels of the
dinucleotide CpG compared with the relatively low levels of CpG present
in higher cells of plants and animals. The DNA CpG content signals , to
the higher cell, the presence of an invading pathogen triggering defense
responses including inflammation. The inflammatory response can lead to
pathological impacts on the body. There is a huge number of publications
in this area illustrated by a publication on CpG rich DNA fragments that
induce an inflammatory response in mammals (6). I am not suggesting that
the synthetic genes in GM crops induce effects such as the triggering
inflammation through the CpG effect. What I am suggesting is that the
synthetic DNA should be studied to uncovered any untoward impacts that
it may induce.

In conclusion, the use of proteins produced in bacterial surrogates for
safety evaluation of the transgenic crops containing synthetic genes is
unsound. The synthetic genes are consumed by millions of humans and
animals. Efforts should be made to immediately study the actual
transgenic proteins made in the GM crops and to study the synthetic DNA
itself. Clearly, the regulatory bureaucracy has been overly cooperative
in facilitating release of crops for food and feed that contain
synthetic genes that have never participated in natural selection .


1. Cummins,J. Bt Toxins in genetically modified crops: regulation by
deceit ISIS Press Release 2004 http://www.i-sis.org.uk
2. Gao,Y.Schafer,B,Collins,R,Herman,R,Xu,X,Gilbert,J,Ni,W,Langer,V.
and Tagliani,L. Characterization of Cry34Ab1 and Cry35Ab1
Insecticidal Crystal Proteins Expressed in Transgenic Corn Plants
and Pseudomonas fluorescens J. Agric. Food Chem., ASAP Article
10.1021/jf048744+ S0021-8561(04)08744-8

Web Release Date: December 8, 2004

3.U.S. Evironmental Protection Agency Cry34Ab1 and Cry35Ab1 Proteins and
the Genetic Material Necessary for Their Production in Corn; Notice of
Filing a Pesticide Petition to Establish a Tolerance for Certain
Pesticide Chemicals in or on Food Federal Register 2004,69,53060-3

4. Fischhoff,D. and Perlak,F. Synthetic plant genes US Patent 5,500,365
1996 5.Cummins,J. Synthetic genes in food crops ISIS Press Release 2004

http://www.i-sis.org.uk <http://www.i-sis.org.uk/>

6. Lee,S,Hong,J,Choi,S,Oh,S,Park,K,Kim,J,Karinc,M. and Leeb,S. CpG
oligodeoxynucleotides induce expression of proinflammatory cytokines and
chemokines in astrocytes: the role of c-Jun N-terminal kinase in CpG
ODN-mediated NF-nB activation Journal of Neuroimmunology 2004, 153 , 50–63

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