GENTECH archive 8.96-97



Thanks to the Society for the Promotion of Nutritional Therapy, for the
reproduction of the following article.

Michael Antoniou, MA (Oxon.), PhD
Graduated from Oxford in biochemistry, 1977. Obtained a PhD in molecular
biology from the University of Reading, 1980. Research in basic molecular
biology for the past 16 years with expertise in genetic control mechanisms.
Currently senior lecturer in molecular pathology and head a research group
at one of London's leading teaching hospitals. A major objective is to
contribute to the development of safe and efficacious applications of
genetic engineering within a clinical context ("somatic gene therapy").
Genetic engineering has already made a significant impact in the manufacture
of foods and food supplements. Enzymes derived from genetically engineered
bacteria, yeast or fungi are now routinely used to increase efficiency in a
number of processes. Pectin degrading enzymes increase both the yield  and
the clarity of tinned fruit and fruit juices. Amylases are used in bread
making to ensure better rising of the dough. Rennet which is used in the
production of cheese was traditionally obtained from the calf stomach.
Nowadays virtually all cheese is made from rennet derived from yeast or
bacteria engineered to produce this calf enzyme more cheaply and in
essentially limitless quantities. Earlier this year in the UK, approval was
granted for the manufacture and marketing of riboflavin from genetically
engineered bacteria.

The list of agricultural applications of this technology are even more
extensive and impressive and will therefore be the main focus of this
article. Genetic engineering is said to promise among other things, disease
resistant crops and animals, tastier food with improved nutritional value,
crops that produce their own pesticide and which are herbicide resistant and
crops which can grow in "marginal" soil and climatic conditions with higher
yields to feed the world's ever expanding population. Arguably the greatest
claim of those who endorse the use of genetic engineering in agriculture, is
that it is safe, more precise and a natural extension of traditional cross
breeding methods for generating novel varieties of crops and farm animals.
It is said that this new technology simply gives nature a helping hand with
something that would happen anyway. There is no doubting the power of
genetic engineering to produce more rapidly new varieties of crops and farm
animals. However, since technically speaking traditional methods and genetic
engineering bear little resemblance to each other, how valid are these
claims? Is it as precise and safe as it is made out to be? If there are
inherent dangers with this technology, should we be using it in industrial
processes and agriculture since there are safer alternatives to producing
the same products as well as new varieties of crops and animals?


In order to answer these questions we need to be familiar with some of the
basic principles of genetics and genetic engineering. Genes are discrete
units of  DNA. They are the blueprints which carry the information for the
proteins which in turn make up all the structures and functions
(biochemistry) that constitute the body of any organism from bacteria to
humans. Gene function is extremely tightly controlled so that the right
proteins are made in the correct place within the organism, at the right
time in it's life and in the appropriate quantity. This ensures an
integrated and balanced functioning of all the tens of thousands of
structures and processes that make up the body of any complex organism be it
plant or animal. One will not normally find liver functions in the brain or
leaf specific proteins in the fruit and vice versa! Nature has also evolved
mechanisms whereby cross breeding can only take place between very closely
related species. With traditional breeding methods, different variations of
the same genes in their natural context are exchanged. This preserves tight
genetic control and functions that are vital for health and the integrity of
life as a whole.

In marked contrast genetic engineering allows the isolation, cutting,
joining and transfer of single or multiple genes between totally unrelated
organisms circumventing natural species barriers. As a result combinations
of genes are produced that would never occur naturally. Genetically
engineered ("transgenic") crops containing genes from viruses, bacteria,
animals as well as from unrelated plants have been generated. Furthermore,
the newly introduced gene units are composed of artificial combinations of
genetic material. For example, transgenic tomatoes and strawberries are
under development which contain the "anti-freeze" gene from an arctic fish.
In addition, parts of a plant virus are used to allow this fish gene to
"switch on" in it's new host. All this in turn coupled to an antibiotic
resistance "marker" gene. It is hoped this combination will allow greater
tolerance to frost. This is clearly a great technological advance. However,
the manipulation and transfer of DNA from one organism to another by genetic
engineering can only be carried out with any degree of precision in lower
forms of life such as bacteria and yeast although, as we shall see,
complications may arise even in these cases. The generation of transgenic
plants and animals is currently an imperfect technique. Once injected into
the reproductive cells of an organism, the introduced gene randomly
incorporates itself into the DNA of it's new plant or animal host. This
always results in a disruption, to a lesser degree, of the tight genetic
control and balanced functioning which is retained through conventional
cross breeding. In addition, it is assumed that the introduced gene will
behave in exactly the same way in it's new host as it does in it's native
environment which frequently will not be the case. These effects combine to
always  produce a totally unpredictable disturbance in host genetic function
as well as in that of the introduced gene. Therefore from the standpoint of
the fundamental principles of genetics and the limitations in the
technology, genetic engineering is neither more precise nor a natural
extension of traditional cross breeding methods. If anything the opposite
would appear to be true.


Does the molecular imprecision of genetic engineering matter if quality of
life can be improved without safety or value of the food being compromised?
Unfortunately, disruptions in the biochemistry of the transgenic organism
have already been observed to produce a number of unexpected outcomes whose
unpredictably is the greatest worry. A tomato, for example has been
engineered to have a longer shelf-life but unexpectedly also bruises more
easily which resulted in major problems during it's harvesting. Furthermore,
this tomato may still look good after 6-8 weeks but is lacking in flavour
and has reduced nutritional value. Will the outcome be the same with the
many other ripen-on-demand or longer-shelf-life fruits and vegetables about
to be launched?

The production of novel toxins and allergens poses the most immediate
potential health risk. In 1989 an epidemic of a new disease hit the USA.
Called eosinophilia myalgia syndrome (EMS) it was eventually traced after
several months to the consumption of a particular brand of tryptophan food
supplement derived from bacteria genetically engineered to overproduce this
amino acid. The engineering process had unexpectedly  produced metabolic
perturbations resulting in the formation of a novel toxin from the excessive
amounts of tryptophan present within this organism and which contaminated
the final product. Out of the estimated 5000 people who contracted EMS, 37
died and 1500 are permanently disabled with sickness. Therefore, even in
simple cases such as bacteria where genetically engineered modifications can
be carried out with some precision, unpredictable disturbances in
biochemical functioning with disastrous outcomes can occur. It is therefore
not surprising to find that unexpected toxins and ill effects to the host
have now been documented in the more complex genetically engineered
organisms such as yeast, plants and animals. The only other recorded case of
ill health in humans resulting from a genetically engineered food is from
soya containing a brazil nut protein which, during pre-marketing tests,
still gave rise to reactions in individuals allergic to brazil nuts.
Although overt health problems are potentially rare, it is their
unpredictably  which causes the greatest concern. Therefore, the lessons
learnt from these incidents serve as a timely reminder as hundreds of foods
derived from genetically engineered crops or produced  using  genetically
engineered components are poised for commercialism over the next few years.
Generally, these findings highlight the fact that there are always potential
hidden dangers when artificially manipulating on this finest level of life.


The long term environmental impact of transgenic crops and animals is still
far from clear. Transgenic salmon containing genes from the arctic sea
flounder which grow six times larger and ten times faster are currently
being farmed in Canada and Scotland. Since 20% losses during storms is the
accepted norm on fish farms, this "super salmon" will inevitably escape into
the wild with unknown ecological consequences. The potential problems with
engineered micro-organisms and plants are even greater. There are a number
of ways in which genetically engineered modifications can inadvertently be
spread in the environment. Firstly transgenic crops can simply cross
pollinate with related wild varieties. Secondly many species of
micro-organisms are naturally adapted to pick up on new genetic material
through a number of different mechanisms  which can result in the very rapid
spread of engineered traits including  antibiotic resistance. Plant viruses
have also been demonstrated to readily incorporate into their own genetic
make up engineered genes in transgenic plants. This can not only result in
the rapid spread of engineered properties to other plants but also the
creation of new strains of disease causing viruses with an altered host
range. It is therefore particularly disconcerting to find that an engineered
insect virus possessing the scorpion toxin gene is currently under trials in
Canada for spraying on crops as a broad spectrum pesticide. Most transgenic
crops that have been produced or are under development, are engineered to be
resistant to herbicides or to generate their own pesticide. Field trials in
Scotland and Denmark using transgenic, herbicide resistant oilseed rape,
have already demonstrated efficient cross pollination with related, normally
weedy wild brassica varieties within a single growing season generating
herbicide resistant "superweeds". Similar findings have been recorded with
potatoes. Transgenic cotton containing the Bt bacterial pesticide gene grown
in the southern USA this year, still resulted in millions of dollars in
losses to the farmers from bollworms. Experiments have shown that the
continued presence of a pesticide on plants, as is the case with genetically
engineered varieties, results in the more rapid appearance and maintenance
of highly tolerant pests which may even have contributed to the cotton
disaster. A number of crops are also being generated for growth
characteristics such as wheat that can fix it's own nitrogen and therefore
require less artificial fertiliser, or rice that can grow in marginal salty
waters. The spreading of these properties to relatives through cross
pollination can result in immeasurable ecological disturbances as wild
plants are displaced by these more hardy varieties possessing engineered
traits. Transgenic crops would therefore appear to have a built in
obsolescence. They may lead to reduced use of herbicides, pesticides and
artificial fertilisers in the short term but an even greater dependence on
agrochemicals in the longer term as resistant weeds and insects rapidly
appear in addition to other ecological disturbances. This clearly results in
higher costs to the farmer and consumer as well as an increase in
environmental pollution.

The use of genetic engineering threatens  to compound an already existing
problem, namely the reduction in biodiversity of food crops. The global
dissemination of select hybrids for cereals and pulses produced by seed
companies in the more industrially developed nations of the world, has
already replaced most traditional varieties. Earlier this century there were
more than 100 000 varieties of rice grown in the world, each one ideally
adapted to the local conditions where it was propagated. The "green
revolution" has now reduced this to only 10-15 000 varieties. In addition, a
recent report by the National Research Council (NRC, Washington DC, USA)
focused on how indigenous crops in Africa such as fonio, pearl millet and
African rice have been discarded as inferior in favour of Asian rice and
European and American imports of maize and wheat. The wide scale
introduction of a few genetically engineered types will reduce this crop
biodiversity still further. This could have catastrophic consequences on
world food supply if, for example, an engineered pest resistant crop was to
be destroyed by the rapid appearance of tolerant insects. It was a lack of
crop diversity that resulted in the Irish potato famine 150 years ago!
Furthermore, it turns out that the indigenous African grains are far from
inferior and are not only nutritious but also well adapted to the harsher
growing conditions experienced in many parts of this continent. It would
therefore appear to be far more sensible to adopt the NRC's suggestion of
developing these natural varieties to feed Africa's burgeoning population
rather than waste effort producing genetically engineered wheat, maize or
rice to withstand climatic and geographical conditions which they cannot


There are three advisory committees established by the government and which
are responsible for assessing the risks to health and the environment of
genetically engineered organisms (GMOs) and food products in general. All
three report to the Department of the Environment and the Ministry of
Agriculture Fisheries and Food. The release of GMO's be it bacteria,
viruses, plants or animals must be approved by the Advisory Committee on
Releases to the Environment (ACRE) who must be satisfied that no great
danger is posed by it's release. The safety of genetically engineered food
and food products produced using genetically engineered components and
processes, is assessed by the Advisory Committee on Novel Foods and
Processes (ACNFP). If a product receives safety clearance by the ACNFP, it
is then referred to the Food Advisory Committee which makes recommendations
on matters regarding the labelling, composition and chemical safety of these
food products.

With regards to health risks, the ACNFP demands a very strict assessment of
the levels of known toxins and allergens. Unfortunately, there is no
requirement for general toxicity testing akin to that used for
pharmaceuticals. This may lead to unexpected, unknown toxins or novel
allergens only being discovered if a health problem arises. Furthermore,
food processing which either destroys or removes the genetic material and
it's protein product is assumed as being safe. Nevertheless, toxins and
allergens may be present in the final product. Interestingly, the tryptophan
food supplement disaster already discussed would occur even under these
current rulings due to the fact that it was caused by an unexpected, new
toxic contaminant present in the final, presumed pure product devoid of DNA
and proteinaceous material. It therefore would require neither toxicity
testing nor, as we shall see, labelling.


At present, only products which are, or contain "live" GMOs (e.g. salad
vegetables, fruits, yoghurt), those deemed to be nutritionally
"substantially different" from the parental non-engineered organism and
those which contain genetic material from human or animal sources which may
be objectionable on religious or ethical grounds, need be labelled.
Genetically engineered modifications for "enhanced agricultural performance"
(e.g. herbicide and pest resistance), and processed food products derived
from GMOs (e.g. oil from soya beans or oilseed rape), those which have used
GMOs a part of their production (e.g. yeast in bread baking) or use products
derived from GMOs (e.g. enzymes from bacteria in fruit juice production;
calf rennet from yeast in cheese making, need not be labelled. Food
processing which destroys or removes the genetic material and the proteins
derived from it is assumed to be safe and does not require labelling.

Fortunately for those who have reservations about engineered food, earlier
this year the Codex Alimentarius Committee on Food Labelling which sets
international standards, ruled that genetically engineered food could not be
labelled as "organic" even if grown under organic husbandry conditions.

It is clear that under this current UK and soon to be introduced EU
legislation, very few genetically engineered foods are required to be
labelled. In the vast majority of cases it is being left to food producers
and retailers as to whether a product should be labelled or not. Most major
retailers have stated that they will label all such products although some
discrepancies have already emerged. Only the Co-op supermarket outlet labels
it's cheese as being derived from genetically engineered rennet. No tinned
fruit or fruit juice is labelled as using enzymes from engineered
micro-organisms as part of it's manufacture.

The greatest concern is that the producers of commodity products such as
cereals, grain, pulses and oilseed rape are not in favour of labelling and
therefore not prepared to segregate engineered from natural varieties. This
in turn makes it very difficult for food processors and retailers to know
what is or is not engineered and to know what to label accordingly. This
includes the engineered herbicide resistant soya beans and pest resistant
maize harvested this autumn in the USA and the herbicide/pest resistant
oilseed rape in Europe. Products from these crops are extensively used in
the food processing industry. Soya bean ingredients (flour, protein, oil,
lecithin) are added to 60% of all processed foods whereas components derived
from maize (flour, starch, corn syrup) are included in approx. 50% of
processed foods. Rape seed oil is inexpensive and widely used. Therefore,
unless legislation is passed to ensure segregation, it will be virtually
impossible to avoid genetically engineered components in our food even in
the very near future. Arguments concerning the impracticality of segregation
are untenable in the face of  public announcements  by wholesalers and
exporters in the USA that they are quite happy to provide segregated soya
beans if there was sufficient demand. In addition, simple and extremely
sensitive tests are being offered by a US company to check batches of grain
and pulses for the presence of genetically engineered varieties.

A full disclosure labelling of genetically engineered food is required for
two reasons. Firstly, labelling will protect the consumer's democratic right
to know what they are eating and allow them to make an informed choice as to
whether to buy these products. Secondly, without labelling it would be
difficult if not almost impossible to trace any health problems that may
arise given the diversity of people's diets. The source of the contaminated
tryptophan which caused the EMS tragedy took several months to trace since
the product was not labelled as being derived from a genetically engineered
bacterium. Also, even the presence of small amounts of an allergen in a food
product can cause a severe reaction in a sensitive individual who clearly
needs to avoid it.


Generating new crop hybrids for higher yields has been the dominating factor
in modern agriculture for many years. However, quantity has been in many
cases at the expense of quality. High yielding varieties can not only be
deficient in flavour but also in nutritional value. It is perhaps ironic
that food producers are now relying on genetic engineering  to put the
"taste" back into food rather than returning to more traditional varieties.

When analysed from the viewpoint of the fundamental principles of molecular
genetics, it is evident that the generation of genetically engineered plants
and animals  is an imprecise technology with inherent potential dangers.
Foods derived using this technology can therefore quite justifiably still be
called "experimental" especially in the absence of data testing for the
unexpected production of novel toxins and allergens. Clearly,
biotechnologists should not forget the basic principles of genetic
functioning or the limitations of the technology as it stands whilst trying
to meet their technical and commercial objectives. There is sufficient
evidence to show that things  can still go drastically wrong. Furthermore in
the absence of full mandatory labelling of engineered foods, the public
would appear to unwittingly be participating in a vast global food
experiment whose outcomes are far from certain.

Although very few genetically engineered crops are currently approved or
already marketed, if current trends go unabated within the next 5-8 years
most food plants of the world will be modified by this technology. This
includes not only major commodity items (cereals and pulses) but also common
fruits and vegetables including apples, strawberries, cantaloupe melons,
grapes, sugar beet and potatoes to name but a few.

Those who do not want to participate, at least for the time being , in the
"experiment", will find it increasingly difficult to avoid engineered foods.
Given the ruling of the Codex committee, eating only organically grown food
would appear to be the easiest way of avoiding them. The engineered soya
beans and maize are due to arrive in Europe from the USA this November [they
are of course already here as this was written last year] and will find
their way, as discussed, into 60% of processed foods. A boycotting of these
processed foods, unless reassurances can be given about the origin or
variety of their soya and/or maize, would appear to be the only course of
action open to the concerned individual.
Last but not least we must also remember that unlike chemical pollutants and
other problems in the food chain such as a BSE epidemic, once genetic
pollution causing toxins/allergens and ecological disturbances is in our
soil, crops, animals and their wild relatives, it cannot be cleaned up or
simply allowed to decay and will be passed on to all future generations
indefinitely. Given that we have viable and safer alternatives is it worth
taking the risk?



Toxin and Allergic Effects
Eosinophilia-myalgia syndrome and trytophan production: a cautionary tale.
Mayeno AN and Gleich GL (1994) Trends in Biotechnology 12: 346-352

Enhanced accumulation of toxic compounds in yeast cells having high
glycolytic activity: a case study on the safety of genetically engineered yeast.
Inose T and Kousaku M (1995) International Journal Food Science Technology
30: 141-146

Identification of brazil-nut allergen in transgenic soybeans.
Nordlee JA, Taylor SL, Townsend JA, Thomas LA and Bush RK (1996) The New
England Journal of Medicine 334: 688-692

Allergies in Transgenic foods-questions of policy.
Nestle M (1996) The New England Journal of Medicine 334: 726 727

Allergenicity assessment of foods derived from genetically modified plants.
Fuchs RL and Astwood JD Food Technology February 1996: 83-88

Ill effects in Plants Caused by Transgenes
Manipulation of flower structure in transgenic tobacco.
Mandel, MA et al. (1992) Cell 71: 133-143

Forcing expression of a soybean root glutamine synthetase gene in tobacco
leaves induces a native gene encoding cytosolic enzyme.
Hirel, B., Marsolier, MC., Hoarav, A., Hoarav, J., Brangeon, J., Shafer, R.
and verma, D.P.S. (1992) Plant Molecular Biology 20:207-218.

Environmental hazards
Transgenic plants on trial.
Kareiva P. (1993) Nature 363: 580-581

Ecology of transgenic oilseed rape in natural habitats.
Crawley MJ et al. (1993) Nature 363: 620-623

Gene dispersal from transgenic potatoes to conspecifics: a field trial.
Skogsmyr I (1994) Theoretical and Applied Genetics 88: 770-774.

The risk of crop transgene spread.
Mikkelsen TR, Andersen B and Jorgensen RB (1996) Nature 380: 31.

Inheritance and stability of resistance to Bacillus thuringiensis
formulations in diamond back moth, Plutella Xylostella (Linnaeus)
(Lepidoptera: Yponomeutidae).
Hama H, Suzuki K and tanaka H (1992) Applied Entomology and Zoology 27: 355-362.

Complementation of coat-protein defective TMV mutants in transgenic tobacco
plants expressing TMV coat protein.
Osbourn JK, Sarkar s and Wilson MA (1990) Virology 179: 921-925.

Recombination between viral RNA and transgenic plant transcripts.
Greene AE and Allison RF (1994) Science 263: 1423-1425.

Bt cotton infestations renew resistance concerns.
Fox JL (1996) Nature Biotechnology 14: 1070.

Human Genes into Plants
A mammalian 2-5A system functions as an antiviral pathway in transgenic plants.
Mitra A. et al (1996) Proc. Natl. Acad. Sci. USA 93: 6780-6785.

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