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[SANET-MG] reply to codex questionnaire
I have enclosed our response to the codex questionnaire on GM crops
modified for nutrition and health. The response is long so I have put
the reply into two separate mailings, one for each codex question.
Question 1
November 27, 2005
Reply to Questionnaire Codex Guideline for the Conduct of Food Safety
Assessment of Foods Derived from Recombinant-DNA Plants
Professor Joe Cummins
Dr. Mae-Wan Ho
For Independent Science Panel*
Question # 1: In your view, what would be important factors in
determining if a recombinant-DNA plant is to be considered a A
Recombinant-DNA Plant Modified for Nutritional or Health Benefit@, and
as such within the scope of the proposed annex?
Answer: First, it is essential to exclude the evaluation of
pharmaceutical products such as oral vaccines, immune modulating
proteins, hormones, antimicrobials and growth factors from the present
considerations. Such products should be considered separately and
reviewed independently from the current annex; they are inherently
hazardous and require special consideration under a separate annex.
Plants modified for nutritional or health benefit should include only
those with enhanced vitamins, minerals, antioxidants (for example plant
phenolics (flavonoids) known to fight cancer) and enhanced primary
metabolites such as essential amino acids and health promoting reduced
linolenic fats. Recombinant genes derived from a plant used to modify
another plant species should not automatically be deemed safe for
humans. This is highlighted in a recent investigation in which a protein
from bean was found immunogenic when expressed in pea [1]. Specifically,
immunological assessments carried out for the first time on a transgenic
protein revealed that post-translational processing subsequent to gene
transfer into an alien species introduced new antigenicities that turned
a previously harmless protein into a strong immunogen. In addition, the
transgenic protein promoted immune reactions against multiple other
proteins in the diet.
As practically all the transgenic proteins involve cross-species gene
transfer, they will be subjected to different post-translational
processing, and hence they too, will have the potential to become
immunogenic. And yet, none of the transgenic proteins that have been
commercially approved has been tested. This omission is a most serious
public health issue, and the Independent Science Panel has already
called for an immediate ban on all GM food and feed until proper
assessment on the immunogenicity of all the transgenic proteins has been
carried out [2]. This should apply all the more so to GM crops coming to
the market that are meant for human consumption.
Nutritional enhancement and traits for improved health may be developed
using conventional breeding or marker assisted selection then those
traits combined with recombinant traits such as herbicide tolerance
and/or insect resistance. Monsanto’s Vistive soybean, for example,
combines natural genes reducing the oil content of linolenic acid, but
also has transgenes conferring the Roundup Ready trait. The transgene
activity is known to affect the precursor pools leading to formation of
trans fatty acids [3]. The point is that when nutritional or health
traits are combined with transgenic ones, the interaction of the two
should be fully evaluated. Interactions between transgenic nutrition and
health traits and other genetic modifications within a cultivar should
be carefully evaluated, as should interactions between conventional
nutritional or health traits with transgenes in recombinant strains with
which they are combined.
A number of nutritional- and health-related transgenic plants are being
developed (see Box). We must ask if these developments provide real
benefits for people, and whether there are safer, cheaper and more
effective alternatives for producing the nutritional/health benefit.
More importantly, in every single case, it is necessary to assess the GM
plant, the transgene and protein for toxicity and immunogenicity, for
reasons given above.
Nutritional and health-related GM crops under development
• Cassava is being genetically modified to enhance activity of an enzyme
that destroys the toxic cyanogenic glycosides [4]. But these compounds,
which release cyanide when eaten, are normally destroyed if the cassava
is adequately processed.
• A sweet protein, brazzien, was produced in GM maize by introducing a
gene from an African plant. The sweetener was proposed for use in the
food industry [5].
• A synthetic gene for porcine alpha-lactalbumin was introduced into
maize along with a signal peptide from maize for localizing the protein
to the endoplasmic reticulum. The pig-corn was supposed to provide a
more digestible plant protein for humans [6].
• Human milk proteins genes were used to modify maize, supposed to
improve human nutrition [7].
• Enhanced seed phytoesterol was achieved by transferring a gene from
the rubber tree to tobacco [8]. The compounds would be used as
cholesterol-lowering foods when food crops are modified.
• Canola was modified as a source of omega-3 fatty acid using fungal
genes [9].
• Very long fatty acids were produced in Arabidopsis using genes from a
tiny alga, a protozoa and a fungus [10].
• Soybean naturally deficient in methionine is being engineering to
remedy the amino acid deficiency in free amino acids and in storage
proteins [11].
• Soybean was modified with a gene from maize, delta-zein, which is rich
in methionine [12].
• Maize was modified with a bacterial gene that provided increased free
lysine in cellular pools [13].
• A grape stilbene synthetase was used to modify tomato to reduce lipid
peroxidation [14].
• Maize modified with prentyltransferase from barley seeds resulted in a
large increase in vitamin E [15].
• Golden rice expresses a daffodil gene to increase beta-carotene, which
is then converted to vitamin A. This modification has now been extended
to Indica rice [16]. The golden rice cultivars do not produce sufficient
beta-carotene to fulfill the human requirement for vitamin A, however.
• Fructans are considered important functional foods because they
promote the growth of beneficial intestinal bacteria. Fructans enhance
mineral re-sorption, decrease cholesterol and hence may help prevent
cardiovascular disease, colon cancer and osteoporosis. Onion fructosyl
transferase was used to modify sugar beet, a crop that does not normally
produce fructans [17].
• Deficiencies of iron and zinc in food crops are widespread, and
approaches to increasing trace element uptake or increasing trace
element absorption were reviewed including genetic modification [18]. A
technique called ion genomics has been developed to elucidate all of the
genes involved in mineral nutrition in plants [19]. Iron was fortified
in rice seeds by modifying the iron in the seeds using soybean ferritin
gene expressed in the seed endosperm [20]. Some plant species can
utilize zinc from zinc deficient soils, this ability has been studied to
find out whether or not it can be transferred food crops suffering from
deficiency [21]. A polyhistidine sequence was fused to a rubisco
sub-unit by plastid transformation of tobacco. The polyhistidine
sequence specifically binds zinc, which accumulates at low zinc levels
in the culture medium [22]. The approach may be applied to food crops.
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