GM Food Animals Coming

ISIS Press Release 15/11/06

Foods derived from genetically modified animals 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

Heritable versus non-heritable modifications

The Codex Alimentarius Commission of the United Nations is preparing guidelines for safety assessment of foods derived from recombinant-DNA animals [1], which is a sure sign that GM animal food is coming to our table.

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?”

We present an overview of heritable and non-heritable modifications, which are not as distinct as Codex thinks, and point to risks that have not been seriously considered. This article is base on a report we submitted to Codex [2], Genetically Modified Food Animals Coming , which contains all the detailed references.

Heritable modifications

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 in animals. 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. A 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.

A novel approach was to transfect germ cell tissue in neonatal testis by electroporation, which was then grafted 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 .

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