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[SANET-MG] gm crops for health 3
part 3
gm crops for health?
Minerals
There has been extensive genetic manipulation to improve the mineral 
nutrition of plants for both macronutrients such as calcium and 
nitrogen, and micronutrients such as selenium.
A 3-fold enhancement of calcium in potato tubers was achieved using an 
Arabidopsis calcium exchanger and transporter gene. The exchanger had 
been shortened at the N terminus to eliminate an auto-inhibitory 
regulatory domain of the protein. Two different promoters were tested, 
the CaMV promoter and a cell division cycle gene promoter, both of which 
appeared to have equivalent effects on calcium uptake [58]. The 
modifications did not affect yield or quality of the potatoes. Milk is 
currently the main source of calcium in children’s diet, but is that to 
be soon replaced by fries?
Inorganic nitrogen fertilizer is linked to a variety of problems 
including the pollution of drinking water, harming infants and causing 
eutrification of water and depletion of oxygen for aquatic animals. 
Improving utilization of nitrates by crops should lead to human health 
benefits in terms of cleaner drinking water, which could be offset by 
increased levels of nitrates in crops. The best way to improve nitrate 
utilization by crop plants is to phase out chemical fertilizers in 
favour of organic inputs, which decrease nitrate levels in the water as 
well as in the crop plants, where cancer-fighting antioxidants, mineral 
nutrients and micronutrients are also increased [21, 59] (Organic 
Strawberries Stop Cancer Cells; Organic Farms Make Healthy Plants Make 
Healthy People). So far, there has been little progress in developing 
transgenic crops that take up and utilize nitrogen more efficiently [60].
Iron deficiency in food crops plagues much of the globe, particularly 
Asia. About 40 percent of the world’s women suffer some degree of iron 
deficiency. Pre-menopausal women are most severely affected by iron 
deficiency, while men tend to retain iron. Increased dietary iron is 
desirable and rice is the preferred crop for increasing iron content. 
Mugineic acid phytosiderophores (siderophores are compounds that bind 
metals in the soil and enhance their cellular uptake) iron transporters 
are re-adsorbed by the plant roots. In response to iron deficiency, the 
phytosiderophores are markedly increased. Transgenic rice modified with 
barley genes for the precursors of the phytosiderophore produce elevated 
levels of phytosiderophore and had enhanced tolerance to low iron soil, 
and had a greater yield than conventional rice on alkaline soil [61, 
62]. Constitutive expression of a gene for soybean ferritin in wheat and 
rice resulted in increased levels of iron in the leaves and stems of 
transgenic rice but not the grains [63]. The soybean ferritin gene 
linked to an endosperm specific promoter was expressed in the seeds of 
maize resulting in elevated iron content [64] (Rice in Asia: Too Little 
Iron, Too Much Arsenic). Food crops enhanced with elevated iron content 
must be labelled in the marketplace because iron overload is a 
significant problem in males, and may lead to haemochromatosis, a 
disorder of excessive absorption and storage of iron that could damage 
the liver and other organs, resulting in liver cancer or colorectal 
cancer. One percent of the population may carry a mutation (hereditary 
haemochromatosis) that makes them sensitive to iron overload at 
relatively modest iron intake levels; and there is an association 
between increasing iron stores and risk of cancer [65].
Selenium is essential for humans, but has a toxic side that makes it 
poisonous at relatively low levels. In Australia, selenium is generally 
inadequate for optimum human health, so agronomic bio-fortification of 
food grains has been proposed [66]. In western USA, on the other hand, 
high soil selenium levels are encountered. Seleniun toxicity is caused 
by replacement of protein sulphur with selenium forming selenocysteine, 
which is needed at low levels but toxic at higher levels. A mouse gene 
specifying an enzyme selenocysteine lyase was introduced into the 
Brassica juncea (canola) chloroplast genome to limit accumulation of 
selenocysteine to mitigate selenium toxicity. The transgenic canola had 
a reduced content of selenium in its proteins [67]. Like iron and other 
minerals, selenium is an essential nutrient, but becomes toxic at high 
levels.
It is clear that manipulating single genes to overproduce any mineral 
(or vitamin) is fraught with difficulties as these essential nutrients 
are often toxic at inappropriately high levels. This highlights the 
importance of getting a balanced mineral content in our food, which can 
only be achieved by moving away from unbalanced external inputs of 
chemical fertilisers in favour of organic fertilisers [21, 60].
Fatty Acids
Long chain fatty acids are the focus of a great deal of interest because 
they play an important role in health and nutrition. Long chain 
polyunsaturated acids are vital for human health. Fish and marine oils 
are the main sources of long chain polyunsaturated fatty acids, but 
efforts are being made to modify oil crop plants to produce the 
essential fish fats. The key fatty acids are eicosapentaenoic acid (20 
carbon fatty acid with five unsaturated double bonds) and 
docosahexaenoic acid (22 carbon fatty acid with six double bonds). Genes 
from a marine microalga Isochrysis galbana, an oil-producing fungus 
Mortierella alpina and a green protozoan flagellate Euglena gracillus 
were used to transform Arabidopsis to modify the plant seed oils to fish 
fatty acids. The transforming genes were involved in elongating and 
desaturating the plant fatty acids [68-70]. The crucial long chain 
polyunsaturated fatty acids were synthesized in Arapidopsis, a tiny 
plant grown in small petri dishes, which is thus unlikely to produce 
commercial quantities of the essential fatty acids. The process will 
have to be transferred to oil crops; but why not grow fish instead? Fish 
and vegetables together make a much more satisfactory diet, and 
certainly a more enjoyable meal for most people.
Monsanto engineered canola seeds to accumulate stearidonic acid, another 
long chain polyunsaturated omega-3 fatty acid that has 18 carbons and 4 
double bonds. The transgenic canola was modified with genes targeted to 
the seeds, and included genes for desaturase from the oil fungus 
Mortierella alpina and from canola [71].
USDA and the University of Nebraska created transgenic soybean to 
produce stearidonic acid. The soybean was modified with desaturase genes 
from borage (a tasty salad green) and Arabidopsis, driven by a 
seed-specific promoter from soybean. Stearidonic acid made up 60 percent 
of the seed oil in the modified soybean [72].
Sunflower seed oil has been modified with multiple copies of a 
desaturase gene from castor bean to act on stearic acid, which reduces 
the quality of sunflower seed oil. The transgenic oil had reduced levels 
of stearic acid and was superior to unmodified sunflower oil [73]. 
Antisense technology was used to down regulate a cottonseed desaturase 
gene resulting in enhanced production of desirable oleic acid and 
reduced the content of linoelic acid, which is highly undesirable [74].
The modifications of plant fatty acids are impressive, but the impact of 
the transgenes and transgenic plants on human health remain unknown. As 
discussed earlier, the protein products of transgenes may have 
undesirable effects on the immune system. Metabolic engineering in 
general may create unintended toxins and immunogens. Another factor to 
take into account is that the essential polyunsaturated fatty acids are 
also known to be toxic at high levels. There is good evidence that n-3 
and n-6 polyunsaturated fatty acids are therapeutic at moderate levels 
in the diet but they may be detrimental at high levels by causing 
oxidation stress and forming lipid peroxides which are toxic. Daily 
intake of the polyunsaturated fatty acids above 10 percent of energy 
intake is not recommended [75]. Furthermore, high intake of marine fat 
rich in n-3 polyunsaturated fatty acids may prolong gestation, producing 
high birth weight [76] and gestational exposure to methylmercury in 
fish. The n-3 fatty acids interact with the mercury pollutant found in 
fish and unmask its toxic effects [77].
Amino Acids
Certain amino acids are essential for the human diet because mammals 
cannot synthesize the amino acids. The essential amino acids are 
histidine, isoleucine, leucine, lysine, methionine, phenylalanine, 
threonine, tryptophan, and valine. In addition, the amino acids 
arginine, cysteine, glycine and tyrosine are considered conditionally 
essential. Certain crops, such as maize, are not complete foods or feeds 
because they are deficient in an essential amino acid. Maize is normally 
deficient in lysine. As indicated earlier, high lysine transgenic maize 
was approved for commercial release in 2004. The transgenic lysine is 
modified with a bacterial gene while high lysine maze varieties are 
already available through conventional breeding. The transgenic maize 
differs from high lysine maize derived from conventional breeding, which 
contains storage proteins with elevated lysine. Transgenic maize, on the 
other hand, has lysine elevated in the metabolic pools, and while it may 
provide adequate lysine in fodder, the soluble lysine may be lost during 
processing of the grain [2]. High lysine cereal crops other than maize 
are considered desirable [79].
Methionine is deficient in some food and feed crops, and there are 
efforts to enhance methionine levels in these crops. A sunflower seed 
albumin, rich in the sulphur amino acids methionine and cysteine, was 
used to modify lupine, a significant feed crop in many countries. The 
transgenic construct included a herbicide tolerant gene (Bar) and a gus 
reporter gene. The modified lupine seeds performed significantly better 
than unmodified lupine in feeding trials [79]. Lupine is not the only 
legume deficient in sulphur amino acids as all legume storage proteins 
have low levels of these amino acids, preventing them from being a 
complete diet. Methionine and cysteine were enhanced in alfalfa by 
over-expressing an Arabidopsis cystathionine gamma-synthase gene (the 
first enzyme in the metabolic pathway for methionine). The enzyme was 
driven by a pea chloroplast rubisco promoter, and directed to the 
chloroplast by adding a pea rubisco transit sequence. The modified 
plants were enhanced in both soluble and protein bound methionine and 
cysteine [80].
Maize has a high methionine-rich storage protein that is usually 
under-represented in the seeds. A cis-acting regulatory site giving 
limited messenger RNA stability was replaced by a sequence imparting 
greater messenger RNA stability, resulting in increased levels of 
methionine in transgenic seeds. This provided feed and food that did not 
require addition of synthetic methionine [81]. A bacterial (E. coli) 
serine acetyl-transferase gene, driven by the CaMV promoter, was 
transferred to potato to increase cysteine and glutathione. An 
Arabidopsis transit sequence was added to direct the transgenic protein 
to the chloroplast. The resulting transgenic potato plants had elevated 
levels of cysteine and glutathione. Metabolic engineering was used to 
enhance production of sulphur-containing compounds in potato [82].
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