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[SANET-MG] gm food animals part 1
I am providing ourlong brief to codex in three parts. This is the first.
I wish others to submit comments to codex on this vital matter.
USDA/APHIS and US EPA as well as CFIA Canada seem to be keeping these
important developments close to their chests.It might be a good idea to
urge more public participation in the safety evaluation of gm food
animals in USA and Canada.
gm food animals part 1
Genetically Modified Food Animals Coming
Foods derived from genetically modified animals are far from safe. They
are likely to be contaminated by potent vaccines, immune regulators, and
growth hormones, as well as nucleic acids, viruses, and bacteria that
have the potential to create pathogens and to trigger cancer.
Prof. Joe Cummins and Dr. Mae-Wan Ho
The Codex Alimentarius Commission of the United Nations is preparing
guidelines for safety assessment of foods derived from recombinant-DNA
animals [1]. Comments on the topic can be submitted before 1 October
2006 to Codex Alimentarius Commission FAO Viale delle Terme di Caracalla
00100 Rome, Italy, Fax: +39 06 5705 4593 E-mail: codex@fao.org Copy
to:Dr. FUJII Mitsuru Counsellor, Minister’s Secretariat, Ministry of
Health, Labour and Welfare 1-2-2 Kasumigaseki, Chiyoda-ku 100-8916
Tokyo, Japan Fax: +81 3 3503 7965 E-mail: codexj@mhlw.go.jp . It is
likely that the establishment of food safety assessment guidelines will
be followed by an avalanche of applications for releasing genetically
modified (GM) animals.
Codex distinguishes between heritable and non-heritable genetic
modification of food animals. Heritable genetic modification involves
genetic changes that persist in sperm and egg while non-heritable
modification involves the introduction of modified genes such as
vaccines into the somatic tissue of animals. Codex asks: “Are there
specific food safety questions (e.g. with regard to types of vectors)
that should be considered relative to the assessment of safety of food
from animals containing heritable versus non-heritable traits?”
Our submission for the Institute of Science in Society provides a review
of both heritable and non-heritable genetic modifications of animals for
food, followed by specific comments.
A. Heritable Modifications of Food Animals
Heritable alteration or genetic modification (GM) of food animals has
been achieved since the early 1980s, mostly by injecting naked DNA.
Between 1 and 20 million copies of the transgene (gene to be integrated
into the animal genome) are injected into the embryo pronucleus (the
nucleus before fertilization) or into the egg cytoplasm, with at most
about one percent of injected embryos becoming transgenic animals. The
transgenes integrate randomly, though rare instances of homologous
recombination with host genes may occur.
A number of different vectors have been used to deliver transgenes.
Transposons (mobile genetic units capable of transferring genes) are not
widely used in vertebrates. Lentivirus (lenti-, Latin for “slow”), a
genus of slow viruses of the Retroviridae family characterized by a long
incubation period, can deliver a significant amount of genetic
information into the DNA of the host cell, and are among the most
efficient gene delivery vectors. HIV (human immunodeficiency virus), SIV
(simian immunodeficiency virus), and FIV (feline immunodeficiency virus)
are all examples of lentiviruses that have been used successfully with
farm animals such as chicken, pig and cow. They are about 50 times more
efficient than DNA injection at producing transgenic animals. One
problem encountered is that the long terminal repeats of the integration
vector interfere with the inserted gene’s promoter. Homologous
recombination has been used to produce specific gene “knock outs” by
replacing an active gene with an inactive one. “Knock in” refers to the
integration of a foreign gene at a specific target, disrupting the
target gene by inserting the transgene.
Transgenes are designed according to rules that result in gene
expression in the host animal, such as the presence of at least one
intron, exclusion of GC rich regions, particularly CpG rich motifs. Gene
sequences called insulators are often included; these contain
transcription enhancers and enhancer blockers to avoid cross talk with
adjacent genes, and chromosome openers that modify histones to allow the
transcription machinery to be expressed. Finally, RNAi may be used to
inactivate specific genes either as heritable transgenes or as
non-heritable gene treatments [2]. A lentivirus vector based on HIV
dramatically increased the efficiency of producing transgenic animals,
thereby greatly reducing cost. Foetal fibroblast cells can be modified
and then cloned to produce transgenic animals [3].
A novel approach was to transfect germ cell tissue in neonatal testis by
electroporation, which was then ectopically xenografted onto the backs
of nude mice (nude mice are immune deficient and tolerate grafts from
mammalian tissues). The nude mice, previously castrated, produced mature
transgenic sperm that functioned well in in vitro fertilization to
produce transgenic farm animals. The technique has been used
successfully in cattle, pigs and even humans (though without producing
an actual human as yet). The technique is promoted for humans as a means
of allowing men requiring irradiation cancer treatment to set aside
viable sperm for in vitro fertilization [4-6].
‘Improving’ the nutritional value and health benefits of livestock
Transgenic clones of cattle producing milk with higher levels of beta
casein and kappa casein proteins were created [7]. The casein fraction
of milk contains four proteins in colloidal aggregates in emulsion.
Kappa-casein coats the aggregates, and increasing the concentration of
the protein results in smaller aggregates (a finer emulsion) and
improves processing and heat stability. Beta-casein binds calcium,
increasing calcium content of the milk and also improves processing.
Rare natural forms of beta- and kappa- caseins were used to transform
embryonic fibroblasts with as many as 84 copies of the genes integrated
randomly in the genome. The fibroblasts were then used to produce clones
of the cattle. Nine cows expressing the transgenes produced milk with up
to 20 percent increase in beta-casein and double the level of
kappa-casein. The overall health of the transgenic cattle was not
discussed in any detail, let alone the health impacts of the milk used
as food.
Consumers need to be alerted to a whole range of genetically modified
‘neutraceuticals’, animals and animal products that are supposed to
provide enhanced nutritional value.
Cloned transgenic pigs have been produced rich in beneficial omega-3
fatty acids [8] normally obtained by eating fish. The transgene
consisted of a synthetic n-3 fatty acid desaturase from the roundworm C.
elegans driven by a cytomegalovirus enhancer and chicken beta-actin
promoter, accompanied by a selection marker gene for neomycin
resistance. Pig foetal fibroblasts were transformed and then used to
clone transgenic pigs. The transgenic pigs produced high levels of
omega-3 fatty acids and a significantly reduced ratio of n-6/n-3 fatty
acids. As before, the overall health of the cloned transgenic pigs was
not extensively discussed, nor the health impacts of the transgenic pig
used as food.
Recombinant human protein C was expressed in the milk of cloned
transgenic pigs [9]. Human protein C is an anti-coagulant found in the
blood, and serves as a therapy for many disease states. Foetal pig
fibroblasts were transformed with a fusion gene consisting of the mouse
acidic whey protein and its promoter and terminator into which the pig
protein C gene sequence had been inserted. This results in high
production of human C protein. The transgenic fibroblast nucleus was
cloned to produce pigs with human C protein in their milk. The
transgenic pigs produced the therapeutic protein, which protected the
pigs against blood clot, but with a risk of pulmonary embolism.
Pigs expressing an E. coli salivary phytase produced low phosphorus
manure [10]. Phytase increases the availability of feed phosphorous and
decreases its release in manure, thereby eliminating environmental
pollution by phosphorus.
Transgenic chickens expressing bacterial beta-galactosidase hydrolyze
lactose in the intestine, and to use that sugar as an energy source [11,
12]. Chickens fed lactose-containing foods normally develop diarrhoea,
while transgenic chickens can thrive on lactose containing feed, such as
dairy products or waste products. Early chicken embryos were transformed
using the spleen necrosis retrovirus vector (SNTZ), a
replication-defective vector containing neomycin resistance selectable
marker under the control of a SV40 viral promoter and poly A
transcription termination, and the beta-galactosidase was preceded by a
nuclear-localization signal sequence. Beta-galactosidase activity was
identified in the chicken’s intestinal mucosa. SNTZ is an avian
immunosuppressive retrovirus that infects non-replicating cells, not
only of birds but of some mammals as well. It has an extraordinarily
high mutation rate, and that is not a defect in the
replication-deficient vector.
Transgenic fish
Transgenic fish are poised for commercial release. These will either be
produced in confined land-locked ponds, fish pens in confined fjords or
sounds, or released to open seas or lakes. Landlocked ponds provide
protection from environmental release while fish pens are notoriously
unreliable and tend to harbour sea lice or other parasites and
pathogens. Release to open waters is final and irrevocable and fraught
with uncertainty. It would seem most prudent to limit production of
transgenic fish to landlocked ponds, to avoid or reduce the potentially
deleterious impact of transgenic fish on the general environment.
Fish genes are most frequently used in producing transgenic fish, and
there is a tendency to regard the transgenic fish “substantially
equivalent” to the native fish even though the transgenes originate from
species unable to interbreed with the species receiving the transgene,
and the Codex consultation document [1] acknowledges that, “transgenic
expression of non-native proteins in plants may lead to structural
variants possessing altered immunogenicity.”
“Substantial equivalence” has been discredited as a deceptive and
useless concept [13] (The Case for a GM-free Sustainable World ) that
should no longer be employed in risk assessment of any GMO (see more
detailed critique later). A new policy framework is needed to cope with
the release of transgenic fish to the environment [14, 15].
In 1999, AquaBounty Inc. first applied to the FDA (Food and Drug
Administration) in the United States to release a transgenic Atlantic
salmon. AquaBounty announces that it is also developing fast growing
strains of fin fish known as AquAdvantage™ fish, capable of reducing
growth to maturity time by as much as 50 percent. It is expecting FDA
approval in 2006 and commercial launch in 2009 [16]. The transgenic
Atlantic salmon contains a Chinook salmon growth hormone gene driven by
the ocean pout antifreeze promoter, resulting in a dramatic increase in
growth rate [17]. Scientists have expressed concerns over the release of
sexually reproducing transgenic fish; realistic models show that it can
lead to the extinction of both the natural and the transgenic
populations [18, 19]. AquaBounty has produced triploid transgenic
Atlantic salmon supposed to be 100 percent sterile [20]; however, the
sterility may be “leaky”, and some fertile animals have been produced
[21] (Floating Transgenic Fish in a Leaky Triploid Craft).
Transgenic Coho salmon was constructed by introducing a sockeye salmon
growth hormone gene driven by a sokeye metalothionen-B promoter. The
transgenic animals were hemizygous for the transgene, being F1 animals
from crosses between transgenic and normal animals. The transgenic
salmon consistently outgrew normal animals [22, 23]. Transgenic Coho fry
emerged from gravel nests two weeks earlier than normal Coho, but had a
highly reduced survival rate, as they suffered higher predation than the
normal fry. Adult transgenic Coho survived just as well as the wild-type
Coho [24].
A rainbow trout growth hormone (rtGH) gene was used to produce
transgenic carp [25]. DNA from a cloning vector, pRSV-2, was introduced
by microinjection into cells at an early stage of embryo development.
The recombinant plasmid contained the rtGH gene driven by the long
terminal repeat (LTR) from Rous sarcoma virus (RSV), and additional
apparently non-functional flanking sequences of bacterial DNA. The LTR
functions as an efficient recognition site for initiation of synthesis
of rainbow trout growth hormone protein in transgenic carp. The
transgenic carp had an altered body form and higher proportion of
protein to fat than the wild-type carp, and required high histidine and
lysine ratios in its diet for maximum growth.
Transgenic tilapia constructed with the ocean pout promoter driving a
Chinook salmon growth hormone gene showed greatly enhanced growth [26].
Tilapia is a tropical fish while the ocean pout is an arctic species.
Heat shock induced tilapia triploids resulted in fish ovaries devoid of
eggs, but the testes of rare individual fish contained mature sperm [27].
Transgenic mud loach was created by fusing the mud loach’s beta-actin
promoter to its growth hormone gene. The transgenic fish grew 35 times
faster than the wild type fish, resulting in giant mud loaches that were
ready for market after only 30 days [28].
Transgenic zebra fish have been sold in United States pet shops since
2003 [29] (Transgenic Fish Coming). The transgenic zebra fish were
projected to be capable of over-wintering in US southern and south
western waters [30]. FDA allowed the release of the zebra fish because
the animals did not fall into their jurisdiction. As the animals have
been released, their presence in the natural environment should be
monitored as a model for the release of transgenic food fish.
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