by Institute of Science in Society (Prof. Joe Cummins,
Dr. Mae-Wan Ho and Lim Li Ching)
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. Here's a description of what it is and
why it should be rejected.
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,
Monsanto's 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 Authority's
(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 environment" .
Despite EFSA's 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 approving GT73.
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 animal
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 to target 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
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 ignored
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
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
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 effect
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 UK's 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
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.
Europe's oilseed rape should keep
its GM-free status before it too is contaminated beyond redemption.
1. Agbios Data base product description MON-00073-7 (GT73, RT73)
pp1-3 http://www.agbios.com/dbase.php?action=Show Prod&data=GT73%2C+RT73
2. Canadian Food Inspection Agency Plant Biosafety Office Decision
Document DD95-02:Determination of of environmental safety of Monsanto
Canada Inc.'s Roundup Herbicide tolerant Brassica napus canola
line GT73 1995, pp1-10 http://www.inspection.gc.ca/english/plaveg/bio/dde.shtml
3. Animal and Plant Health Inspection Service USDA Docket no.
98-089-2 Monsanto co. Determination of Nonregulated status for
canola genetically engineered for glyphosate tolerance 1999, pp1-33.
4. ACRE Advisory Committee on Releases to the Environment. Advice
on a notification for marketing of herbicide tolerant GM oilseed
rape, 24 September 2003, http://www.defra.gov.uk/environment/acre/ad
5. 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,
6. "New Europe" blocks U.S. food import, Friends of
the Earth Europe, 16 June 2004, http://www.foeeurope.org/press/2004/GR_16_june_US_food
7. ANZFA Australia New Zealand Food Authority. Draft risk analysis
report application A363 Food produced from glyphosate tolerant
canola line GT73, 2002, pp1-73 http://www.agbios.com/docroot/decdocs/01-290-
8. Ho MW and Cummins JC. GM food & feed not fit for "man
or beast". ISIS Report 29 April 2004
9. Ho MW. GM Science Review deeply flawed. Science in Society
2003, 19, 7-9.
10. Ho MW. GM maize approved on bad science. ISIS Report 25 February
2002; also, Science in Society 2002, 15, 10-25.
11. Ho MW. Questionable stability at JIC. ISIS Report 2 March
12. Ho MW. Letter to the Scottish Parliament Petitions Committee
from ISIS. 28 February 2002.
13. Ho MW. GM rice unstable. ISIS News 9/10, July 2001.
14. US Food and Drug Administration Biotechnology Consultation
Note to the File BNF No.000020 Monsanto's glyphosate tolerant
canola line GT73 1995 pp1-4 http://www .cfsan.fda.gov/~rdb/bnfm020.html
15. Eicholtz D, Gasser D and Kishore G. Glyphosate-tolerant- 5-enopyruvyl-3-phosphoshikimate
synthetase, 1999, United States patent 5,866,775.
16. Cummins J. Synthetic genes in food crops, ISIS Press Release
1 September 2004,
17. 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 Agency Monograph.
18. Cummins J. Transgenic contamination of certified seed stocks,
ISIS report 2003,
19. Ho M. What lurks behind triple herbicide tolerant oilseed
rape? ISIS report 2002,