Monsanto has applied to import its GM oilseed rape GT73 into Europe
for use in animal feed and processing. The Scientific Panel on GMOs of the
European Food Safety Authority has given it a favourable opinion, and there
will soon be a vote on it at the Council of Ministers. Heres a
description of what it is and why it should be rejected.
Prof. Joe Cummins,
Dr. Mae-Wan Ho and
Lim Li Ching
Oilseed rape is a major crop for oil and animal feed
Oilseed rape (Brassica napus) is grown as a commercial crop in 50
countries with a combined harvest of over 40 million metric tonnes. The major
producers of rapeseed in 2000 were China, Canada, India, Germany, France,
Australia, and the United Kingdom. Canola is a genetic variation of B.
napus with low levels of the natural rapeseed toxins glucosinolate and
erucic acid. Canola is grown for its seed, which represents a major source of
edible vegetable oil and pressed cake from oil extraction is also used in
livestock feeds . Oilseed rape is called canola in North America because the
commercial oil-producing varieties were developed in Saskatchewan, Canada.
Monsantos canola GT73 was released commercially in 1995 in Canada
 and the same strain, designated RT73, was released commercially in the
United States in 1999 . Japan approved the release of GT73 in 1995  and
Australia in 2003 . Approval of all releases was based on essentially the
same data sets.
GT73 in the EU
GT73 was notified for food use (as rapeseed oil) in the European Union
(EU) in November 1997, under the simplified procedure of the Novel Foods
Regulation. This means that rapeseed oil from GT73 was considered
substantially equivalent to its conventional counterpart and only
required notification by the company, with no risk assessment or explicit
approval process. Products made from rapeseed oil may include fried foods,
baked foods and snacks.
An application for the import and use of GT73, excluding cultivation,
was submitted in 1998 to the competent authority of the Netherlands. It gave
this application a favourable opinion, and in January 2003 recommended that
GT73 be approved. Several member States raised questions, including the UK, via
its Advisory Committee on Releases to the Environment (ACRE) . One of the
concerns related to increased liver weights in rats fed GT73, compared with
controls (see later).
The European Food Safety Authoritys (EFSA) Scientific Panel on
GMOs was requested to give its opinion on GT73 to resolve the uncertainties. In
February 2004, EFSA gave its verdict that "GT73 oilseed rape is as safe as
conventional oilseed rape and therefore the placing on the market of GT73
oilseed rape for processing and feed use is unlikely to have an adverse effect
on human or animal health or, in the context of its proposed use, on the
Despite EFSAs positive assessment of GT73 for feed and processing,
the regulatory committee could not reach a qualified majority to authorize GT73
in June 2004. There were 43 votes in favour of approving GT73 (Belgium, Czech
Republic, Finland, France, Netherlands, Latvia, Portugal, Slovakia, Sweden), 57
votes against (Austria, Cyprus, Denmark, Estonia, Greece, Hungary, Italy,
Malta, Lithuania, Luxembourg, Poland, UK), and 24 abstentions (Germany,
Ireland, Spain, Slovenia) .
The application now passes to the Council of Ministers, which will make
its decision very soon. If the Council cannot decide, the decision will rest
with the European Commission, which has shown every sign of being in favour of
No event-specific characterization provided of transgene insert
GT73 (RT73) oilseed rape has been made tolerant to the herbicide
glyphosate. Two transgenes were used. The first is the epsps gene coding
for the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), isolated
from the common soil bacterium Agrobacterium tumefaciens, and is a
glyphosate tolerant form of EPSPS. The EPSPS enzyme is part of the important
shikimate pathway involved in the production of aromatic amino acids. When
conventional canola plants are treated with glyphosate, the plants cannot
produce the aromatic amino acids and die, but the enzyme encoded by the
transgene is insensitive to glyphosate.
The second transgene in GT73 codes for a modified version of glyphosate
oxidase (GOX) enzyme. The gox gene inserted into GT73 was isolated from
the bacterium Ochrobactrum anthropi. The GOX enzyme accelerates the
normal breakdown of the herbicide glyphosate into two compounds,
aminomethylphosphonic acid (AMPA) and glyoxylate [1-3, 7]. In the absence of
GOX, unacceptable levels of the herbicide may accumulate in the canola cake in
The two transgenes were introduced into GT73 in a plasmid using the
bacterium, Agrobacterium tumefaciens. The epsps and gox
genes were each driven by the 35S promoter from a modified figwort mosaic virus
and terminated with the 3 (terminal) end of the pea rbcS E9 gene.
The shikimate pathway is located in the chloroplast, so the chloroplast transit
signal peptide sequence from the ribulose-biphosphate carboxylase and EPSPS of
Arabidopsis is used totarget the transgene products to the
chloroplast. According to the company, only the primary genes and the sequences
necessary for their activity in the plant cell were inserted into the canola
cells while sequences from the plasmid such as the plasmid origin of
replication and a gene for streptomycin resistance were lost from the
commercial strain. Monsanto claimed that only one transgene insert is present
, but the exact site of insertion was not reported [3, 5].
After evaluating the initial application submitted by Monsanto, some
member States had requested additional information on the molecular aspects of
the dossier. However, it is clear from the EFSA opinion that no independent
tests were carried out, and the favourable opinion was based solely on
information supplied by the company. Worryingly, the EFSA opinion  stated:
"Comments raised by the Member States on specific molecular detection
methodologies are presently not within the scope of the GMO Panel remit." In
other words, there is no event-specific characterization, and therefore, no
unique method for detecting this GMO for the purpose of identification or
traceability, nor for addressing safety and liability issues that may arise.
The same EFSA dossier revealed that there are molecular changes at the
insertion site, specifically 40 bp of the host genome is missing from GT73
while 22 bp of extraneous DNA of unknown origin is present at the 5
junction of the insert. Nevertheless, these are considered not to pose a safety
risk, based solely on the lack of homology to known toxins and allergens.
No molecular evidence of transgene stability
The transgenes were claimed by the company to be inserted in a stable
and Mendelian fashion. ISIS has pointed out more than once that this claim of
genetic stability - based on a failure to depart from Mendelian
ratios in the offpring generation - is not an acceptable criterion of
genetic stability in the absence of independent ascertainment of the parental
genotypes [8-13]. But EFSA has accepted the same criterion of transgene
stability. It stated : "The inserted DNA is inherited in a stable fashion in
a nuclear chromosome as indicated by a number of parameters, e.g. predicted
Mendelian segregation ratios (over several generations) from crosses between
GT73 and conventional oilseed rape."
Extensive changes in the codons of transgenes from native genes
Few of the regulatory documents have dealt with extensive alterations in
the genetic codes of the native genes in the transgenes inserted into GT73, but
all of them acknowledge that the codes were altered to enhance production of
the bacterial gene products in the plant. The United States Food and Drug
Administration consultation on canola GT73 provided a somewhat fuller
description of the alterations in the bacterial DNA  while the patent for
the EPSPS used in canola GT73 provides an extensive description of the code
alteration . Native genes from bacteria or humans do not function very well
in crop plants because gene expression is influenced by codon bias specific to
plants, mammals or bacteria. For that reason, the genetic code is altered by
genetic engineers to achieve optimum gene expression. The optimized transgenes
used in modified crops are mainly synthetic approximations of the real
bacterial gene . The synthetic genes are very different from the genes that
evolved in bacteria and for that reason their characteristic recombination and
mutation deserves special attention, as does its toxicology and allergenic
potential. However, these factors have been largely ignored by the regulators.
Toxicology & allergenicity tests invalid
Even though the transgenes were altered in DNA sequence from the native
bacterial genes, the proteins actually tested for mammalian toxicity and
environmental safety were not isolated from GT73 but from the bacteria . The
bacterial surrogate enzymes were assumed to be identical to the enzymes
produced in GT73 by cursory observations using techniques such as gel
electrophoresis, N terminal analysis and enzyme activity, even though the
presence of four anomalous amino acids were noted in the bacterial GOX .
Digestibility and degradability were tested with the bacterial proteins in
simulated gastric fluid. And acute toxicity tests in mice were similarly done
with the bacterial proteins.
Allergenicity tests were even less reliable, as they depended on
theoretical evaluations based on assumptions that have been extensively
questioned. For example, the Austrian government, based on an analysis of a
number of applications for GMO approval in the EU, has concluded that no direct
testing of potentially allergenic properties of GM corps and their products has
been carried out . Instead, conclusion that the protein in question is
unlikely to exhibit allergenic properties is largely based on the following
theoretical considerations: the newly introduced protein originates from a
non-allergenic source; there is no significant sequence homology to known
allergens; the protein will be rapidly digested in the intestine; the protein
is not glycosylated; the expression level of protein in the GM crop is low; and
the protein is not new to the human diet. The Austrian government has
questioned each of these arguments and their underlying assumptions in the
light of recent scientific data.
Consequently, these tests were neither meaningful nor valid. Empirical
tests should have been conducted at the very least, on the real proteins
isolated from GT73, not the bacterial surrogates.
The EFSA did include the warning that, "Since cross-reactivity between
GOX and tropomyosin is not ruled out completely, persons allergic to shrimp
meal should be aware of the possibility of hypersensitivity reaction when
working with GT73 oilseed rape."
Inadequate inappropriate feeding trials with unexplained adverse
According to the EFSA opinion , "A satisfactory explanation was
sought for the potentially adverse effect observed in one of the three rat
feeding studies." We believe that this refers to the concerns expressed in
regard to a confidential Monsanto feeding study that showed that rats fed GT73
experienced a 15% increase in their liver weights.
The UKs ACRE and ACAF (Advisory Committee on Animal
Feedingstuffs) had first raised concerns in March 2003 that the difference in
the rats liver weights could not be explained, as volunteered by
Monsanto, by higher glucosinolate concentration in the GM diets compared with
the corresponding control diets . Subsequently, Monsanto provided further
information on this. But both ACRE and ACAF were "not satisfied" that Monsanto
had supported their hypothesis. They demanded a satisfactory explanation for
this potentially adverse response.
However, it appears that EFSA has dismissed those concerns. A list of
uninformative feeding trials was presented on various animals of extremely
short duration in which mostly body weights and sometimes, liver weights were
recorded. No histology was carried out. Because there were no apparent gross
pathological changes in the rat livers following examination at necropsy, EFSA
considered the difference in liver weights an "incidental finding".
The regulatory reviews leading to commercialization of GT73 oilseed rape
without exception discounted the rapid pollution of transgenic crops by wind
spread pollen or by seed dispersal by animals or vehicles. This can happen
during transport, without planting in the field. Escaped seed can
germinate and potentially cross-pollinate with conventional oilseed rape, feral
populations and wild relatives. ACRE had also raised concerns regarding seed
spill, and was "not convinced that seed spill will not occur and that feral
populations will not materialise" .
There is clear and growing evidence that widespread deployment of GM
oilseed rape will lead to widespread contamination of conventional crops. A
2003 report showed that 95% of certified seed stock in western Canada were
polluted to detectable levels with glyphosate tolerance genes and 52% exceeded
the allowable contamination of certified seed . The widespread deployment
of GM oilseed rape for a variety of herbicides is leading to pyramiding of the
genes for herbicide tolerance , creating crops that turn into fertile weeds
that are difficult to eradicate.
Europes oilseed rape should keep its GM-free status before it too
is contaminated beyond redemption.
Opinion of the Scientific Panel on Genetically Modified Organisms on
a request from the Commission related to the Notification (Reference
C/NL/98/11) for the placing on the market of herbicide-tolerant oilseed rape
GT73, for import and processing, under Part C of Directive 2001/18/EC from
Monsanto. The EFSA Journal 2004, 29, 1-19
Spök A, Hofer H, Lehner P, Valenta R, Stirn S, Gaugitsch H. Risk
assessment of GMO products in the European Union: Toxicity assessment,
allerginicity assessment and substantial equivalence in practice and proposals
for improvement and standardization, July 2004, Austrian Federal Environment