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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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