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[SANET-MG] gm crops for health 2
gm crops for health?
Cassava is a staple food for over 500 million people in the tropics. Its
root is rich in starch and contains proteins with a balanced amino acid
composition, but at low concentrations. In order to add a storage
protein with a balanced amino acid composition, a completely synthetic
gene was inserted that had codons optimised for plants, and placed under
the control of the CaMV 35S promoter and the nos terminator. A
hygromycin antibiotic resistance gene served as the selectable marker.
Nutritional improvement of the cassava root was reported [10, 11]. A
synthetic gene expressing a synthetic protein is a novel approach, and
requires extra careful scrutiny, especially with regard to allergenic
and other immunogenic potentials.
The nutritional value of transgenic potato was increased using the seed
albumin gene from Amaranthus hypochondriacus (Prince-of-Wales feather).
The transgene was driven by a tuber-specific promoter for high levels of
protein production in the tuber. The transgenic protein was believed to
be non-allergenic based on a single experiment with mouse pups injected
with tuber, which were found to produce IgG antibodies but not the IgE
antibodies of allergy . IgG antibodies may be associated with
inflammation, which could be quite severe, but that effect was not
studied. We should be extremely wary of transgenic proteins, as even
gene transfer between closely related species will alter the
glycosylation patterns of proteins and hence its immunogenicity. A
harmless bean protein turned into a potent immunogen when transferred to
pea, eliciting serious inflammation reactions in mice [13, 14]
(Transgenic Pea that Made Mice Ill). Such considerations apply to all
transgenic proteins discussed here.
Soybean is an important protein source in both food and feed. However it
is deficient in sulphur amino-acids, particularly methionine. A
methionine-rich maize delta-zein storage protein was used to transform
soybean, but it failed to increase the methionine content of seed flour
. Storage protein was enhanced in rice, but only by introducing
transgenes into low storage protein mutant strains that had “room” in
the seed for the transgenic protein .
Enzymes for improved food processing
Glutenin is a major storage protein in barley. Barley is malted to make
beer. During malting, glutenin is digested by a beta-glucanase enzyme.
The heat stability of the enzyme can be problematic during industrial
scale malting. A heat stable hybrid enzyme was made from genes of two
bacillus bacteria species, with codon adjustments in the DNA sequence to
enhance protein synthesis in barley. The synthetic hybrid gene is
reported to have improved the malting characteristics of the transgenic
barley [17, 18], but the fate and safety of the transgenic glucanase is
As in the enhancement of storage proteins, genetic engineering for
improved food processing requires much more in-depth research. Marker
assisted selection may be the best way forward, as has been used in
improving the carbohydrates of cereals .
Cancer fighting and health promoting nutrients
There is a growing effort to enhance production of cancer fighting
antioxidants and related plant products that reduce the risk of cancer
and improve health in many ways. The evidence that organically grown
crops are richer in cancer fighting antioxidants [20, 21] (Organic
Agriculture Helps Fight Cancer; Organic Strawberries Stop Cancer Cells)
seems to have spurred biotechnologists on to create GM crops with
enhanced levels of these compounds. Flavonoids are the plant
antioxidants that have received the most attention among
biotechnologists. In feats of metabolic engineering, novel structural or
regulatory genes, antisense or sense suppressing genes, have all been
introduced in efforts to enhance flavonoid production .
Tomato has been the first target. Red wine is rich in the flavonoid
stilbene, thought to be responsible its health benefit in preventing
heart disease, and much effort has been devoted to metabolically
engineering tomato to produce high levels of stilbene. Stilbene is
provided by a gene from petunia flower, which was up regulated in tomato
fruit by regulatory genes from maize. To further increase flavone
production, genes from grape, alfalfa and the flower Gerbera were also
incorporated into the tomato, resulting in the production of high levels
of health related flavonoids . But the safety of the transgenic
tomato containing so many transgenes has not been addressed.
In another experiment, phenolic precursors of the health related
flavonoids, lignans and phenols were enhanced in tomato by down
regulating a competing metabolic pathway using RNAi to inhibit the gene
for cinnanomyl-CoA reductase . The use of RNAi in genetic
engineering food crops and animals has been put into question by the
recent observation that RNAi caused excessive fatality in mice due to
the over-saturation of RNAi pathways [25, 26] (Gene Therapy Nightmare
The human C-reactive proteins are associated with cardiovascular risk,
mice modified with human C-reactive proteins fed transgenic flavonoid
tomato showed a greater decrease in C-reactive protein than mice fed
conventional tomato .
Tomatoes transformed with the grape stilbene synthase gene driven by the
CaMV promoter to provide constitutive synthesis showed increased
ascorbate and glutathione; the soluble and total antioxidant activity
was enhanced while lipid peroxidation was decreased .
Engineered polyamine accumulation in tomato enhanced phytonutrient
content, juice quality and vine life [29, 30]. The problem with
polyamine accumulation is the impact of the polyamines putresine and
cadaverine, which are well known to impair human health  (Drought
Resistant GM Rice Toxic?); and hence the promoters of genetically
modified wine yeast claim that its greatest benefit is in decreasing
polyamine content of the wine. Perhaps, eating high polyamine tomatoes
will cause severe hangovers?
Tomatoes were also modified with the genes for enzymes that enhanced
production of phytosterols by altering the isoprenoid pathway. The genes
influencing isoprenoid formation were isolated from Arabidopsis and the
bacterium E. coli. A chloroplast transit gene from tomato was attached
to the isoprenoid genes, allowing both cytoplasmic and chloroplast
isoprenoid pathways to be enhanced, and the modified tomatoes produced
elevated phytosterols .
Tomatoes are not the only crop to be genetically modified for human
health benefits, apple too, has been modified to enhance stilbene
synthesis. A gene for stilbene synthase from grape, with the
wound/pathogen inducible promoter also from grape, was introduced into
apple along with the bar gene for herbicide tolerance driven by the nos
promoter. The transgenic apple showed an increase in the stilbene
reveratrol and in total flavonoids .
Seed phytosterol levels were enhanced in tobacco using a shortened gene
for a rubber tree enzyme 3-hydroxy-3-methyl-CoA reductase (the gene was
shortened to remove a cell membrane binding domain to increase activity
in seeds). Phytosterol was increased more than 3 fold to 3.5 percent of
the seed oil . Presumably, such constructs will be transferred to
food oil crops such as canola, soybean or maize. Metabolic engineering
of proanthocyanidins using genes for anthocyanidin reductase and for the
Myb protein transcription factor from Arabidopsis provided a way to
enhance the (epi)-flavan-3-ol antioxidants. The antioxidants not only
provide health benefits to humans, but also prevent bloating in
ruminants. Tobacco was transformed to produce quantities of antioxidant
capable of preventing bloating in ruminants. Anthocyanidin reductase
alone enhanced antioxidant production in a forage legume annual alfalfa,
Medicago truncatula, but the levels were not sufficient to prevent
bloating in ruminants . It is worth mentioning that the Myb family
of transcription activators was first discovered as a viral oncogene
(cancer-associated gene). Even though the factor is prevalent in plants,
its amplified use in transgenic food and feed requires thorough risk
assessment and safety testing.
A 2004 review of micronutrients in staple food crops and plant breeding
for improvements  identified a crisis in the availability of certain
micronutrients globally. Children (primarily the poor) may be dying from
deficiencies of iron, zinc and vitamin A, in particular. The problem is
best addressed through agriculture, and biotech proponents have put
forward solutions; though they are certainly not the only solutions.
Sustainable farming practices that emphasize internal organic inputs can
address the problem of micronutrient deficiencies across the board,
without the need for genetic modifications [21, 37] (Dream Farm 2 -
Story So Far).
Carotenoid, the precursor to vitamin A, can be over-produced in plants
by either direct insertion of transgenes or by altering the flux of
metabolites to carotenoid synthesis . “Golden rice” was promoted as
the answer to vitamin A deficiency. The entire beta -carotene
biosynthesis pathway had been engineered into rice endosperm in a single
transformation step. The genes for phytoene synthase (psy) and lycopene
beta-cyclase (beta-lcy) originated from the daffodil and the gene for
phytoene desaturase (crt1) from bacteria . The daffodil gene psy was
subsequently replaced with maize psy to enhance synthesis in rice.
Recent versions of golden indica rice used an endosperm-specific
promoter for psy and CaMV promoters for beta-icy and crt1. Selection was
done using a mannose medium in cell culture, based on co-transformation
of the rice with a phosphomannose isomerase gene driven by a cestrum
yellow leaf curling virus promoter. Mannose selection depends on the
enzyme phosphomannose isomerase converting mannose-phosphate, which
cannot be metabolised by the plant cell, to fructose-phosphate, which
can be metabolised. Unmodified cells accumulate mannose-phosphate,
causing them to die from starvation. Mannose selection avoids antibiotic
resistance marker selection and the carry over of resistance genes into
food. Antibiotic resistance markers have also been removed from golden
indica rice by cross breeding and selection .
The Institute of Science in Society critically reviewed golden rice in
2000 . Among the major concerns was that the rice produced too
little beta-carotene to relieve the existing dietary deficiency. Since
then, golden rice strains have been improved, but still fall short of
relieving dietary deficiency. On the other hand, increasing the level of
beta-carotene may cause vitamin A overdose for those consuming a normal
balanced diet with multiple carotene sources. Vitamin A supplements
taken during pregnancy can cause birth defect, and even moderate to
small doses may induce birth defects (perhaps subtle) during early
gestation . In fact, both vitamin A deficiency and supplementation
may cause birth defects , and it seems that the developers of golden
rice are caught between a rock and a hard place. This is where labelling
is absolutely necessary if golden rice is to be sold in the market, to
alert sensitive people of its potential adverse impacts.
Vitamin E genetically engineering has begun. Plants are the source of
vitamin E, a class of compounds called tocochromanols comprising four
tocopherols and four tocotrienols. Corn seed oil, soybean seed oil and
wheat germ oil are all rich in tocopherols. Vitamin E enhancement has
been achieved by mutation and by genetic manipulation. Arabidopsis has
been the main source of genes to enhance production of vitamin E by
over-expression in Arabidopsis, canola and soybean. Further metabolic
engineering of the tocochromanol pathways may lead to greater production
of the most significant tocopherols [44, 45]. Vitamin E supplementation
has been promoted for preventing heart disease and cancer  and in
treating cancer . However, vitamin E supplementation caused
significantly elevated ovarian cancer in one study , while another
major study found that high dosage supplementation increased all-cause
mortality and should be avoided . Like vitamin A, vitamin E
over-production in food crops is of dubious value, and may indeed be
Vitamin C is commercially synthesized from glucose. The vitamin has been
produced in modified bacteria and yeast and these approaches may have
some limited advantage over chemical synthesis . Plants have been
subject to metabolic engineering to over produce vitamin C, but the
increases have been very modest .
Folate levels have been enhanced in Arabidopsis using the bacterial gene
encoding the enzyme GTP cyclohydrolase , but with yet no success
when transferred to crop plants . Folate enhancement is a global
public health issue. In Canada, USA and Chile, flour is fortified with
folate, resulting is a striking decrease in neural tube birth defects
while in Europe, where fortification is not mandatory, there has been no
decline in neural tube defects . In an area of China where neural
tube defects appeared in 1.4 percent of births, a public information
campaign was run to promote folate supplement for women of childbearing
age, but the campaign failed. Folate fortified flour is inexpensive and
would probably have prevented the birth defects . In the immediate
future, mandatory supplementation will prove more effective than genetic
B vitamins include riboflavin (B2) and pantothenate (B5). Their
metabolic pathways in crop plants are known, but there has been no
success as yet to engineer over- production of the vitamins in food
crops [56, 57].
The metabolic pathways of vitamin synthesis in food crops are well
understood. This knowledge can be exploited for marker assisted breeding
to enhance vitamin production much more profitably than genetic
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