Biosafety of transgenic microorganisms for animals

Introduction: with the penetration and development of modern biotechnology into the field of veterinary science, transgenic technology related to disease prevention and control has become one of the most rapid development and the best application prospects in the 1990s Animal microorganisms are closely related to animal and human health and ecological environment Therefore, the safety problems of genetically modified microorganisms for animals in their research, development and utilization, especially the potential danger to human beings, animal health and ecological environment, have attracted the attention and concern of scientists and the public Understanding these problems, recognizing the possible risks and their degree, and taking corresponding safety management, prevention and control measures will contribute to the better development of Veterinary Biotechnology Transgenic microorganisms for animals mainly include live vaccines for animals and feed additives for animals The safety problems mainly lie in the potential harm to human, animal health and ecological environment 1、 Potential harm to human and animal health What kind of harm might transgenic microorganism for animal cause to human and animal health? What is the severity of the disease (such as the severity of symptoms, the condition after recovery, the immunity of people or animals, whether it causes epidemic, etc.)? At present, the scientific level is still difficult to give an accurate answer However, according to the long-term application experience of conventional live attenuated vaccine at home and abroad, combined with some experimental research data accumulated in recent years on the safety of genetically modified microorganisms, the potential harm of genetically modified microorganisms for animals to human and animal health can be divided into the following three main aspects: 1 The pathogenicity of transgenic microorganism to human and animal mainly refers to its ability to infect and cause human and animal diseases, including toxicity, carcinogenesis, teratogenicity, mutagenicity, allergy, etc In the transgenic work, people can consciously and purposefully select and control the receptor microorganisms, foreign genes and marker genes, but the multi validity and secondary effectiveness of genes should sometimes produce unpredictable changes, which may increase the new pathogenicity or enhance the original pathogenicity compared with the donor and receptor microorganisms 2 Drug resistance is a common problem in the treatment of diseases The problem of resistance to antibiotics is particularly prominent Therefore, the resistance of microorganisms, genes and their products to antibiotics and other major drugs involved in the transgenic work naturally attracts more attention People are concerned that the resistance gene of transgenic microorganism may lead to the resistance of human and animals to antibiotics and other drugs, not only because the relevant transgenic microorganism may directly contact with human and animals, but also because the resistance gene carried by the transgenic microorganism or its plasmid may make other pathogenic micro genes more closely related to human and animals through gene transfer Organisms get the gene, which causes more trouble Therefore, in the transgenic work of animal microorganisms, scientists try to avoid using microorganisms and marker genes that are resistant to common and important antibiotics and other major drugs used by human and livestock; even if it is necessary to use resistance genes as marker genes in the work, some new technologies are adopted to make them unable to express or even dissociate automatically, so that human and animal health can be achieved Better protection 3 Food safety animal is one of the important sources of human food Therefore, people have doubts about the safety of animal products as human food after the application of transgenic microorganisms in animals First of all, whether the transgenic microorganism causes cancer, teratogenesis and mutation after entering the animal body, and whether the human consumption of such animal products has an impact on health Secondly, whether the expression products of transgenic products remain in animal products, and whether human health is affected after eating These questions need to be clarified by scientific research 2、 The potential harm to the ecological environment is still superficial Therefore, the impact of genetically modified microorganisms on the ecological environment is still controversial in the scientific community (including ecologists) When transgenic microorganisms are used in animals, microorganisms can be released to the environment through digestion, respiration and other systems, which may have adverse effects on the environmental quality or ecosystem At present, the environmental impact of transgenic microorganisms is mainly considered in the following five aspects: 1 Pathogenicity and toxicity: transgenic microorganisms for animals in the environment may have certain pathogenicity and toxicity to animals (including target animals, non target animals and invertebrates) and plants, or may produce stronger or new pathogenicity and toxicity compared with donor microorganisms and recipient microorganisms Ronald et al (1996) reported that both the PRV gene deficient vaccine strain and the wild-type virulent strain could survive and reproduce in the body of non target raccoon, which provided a prerequisite for gene recombination between the two strains, and then led to the enhancement of virulence 2 The survival competitiveness of microorganisms in the environment includes viability, fecundity, long-term viability, colonization, competitiveness, adaptability and resistance Generally speaking, the stronger these capabilities are, the more likely microorganisms are to have an impact on the ecological environment Does transgenic microorganism have the survival competitive advantage that naturally occurring microorganism does not have? Can one or more local microorganisms be reduced to the extent that they have a serious impact on the ecological environment and biodiversity through competition for ecological sites and nutrients? Even after these microorganisms enter into human or animal body, does it affect the normal intestinal flora? People can't give a completely positive or negative answer yet However, some experimental results show that, except for a few cases, the survival, colonization and competitiveness of most transgenic microorganisms and their non transgenic parents (receptor microorganisms) in the natural environment are basically the same, and they do not have a special ecological competitive advantage Even in quite a number of experimental conditions, the survival competitiveness of transgenic microorganisms is better than that of non transgenic ones The survival competition ability of transgenic microorganism is weaker than that of non transgenic microorganism 3 Transmission and diffusion ability: the transmission and diffusion ability refers to the ability of microorganisms to transfer in a short or long distance through soil, air, water, plant residues, insects or other animals The stronger the spread ability of microorganisms, the greater the impact on the environment The ability, mechanism and potential harm to the ecological environment of transgenic microorganism for animal in and out of the use area are very important indicators of biosafety evaluation 4 Genetic variation ability Genetic variation ability refers to the genetic stability and adaptive variation or mutation ability of transgenic microorganisms and their genes (especially transgenes) under different physiological and ecological conditions Because of the rapid growth and reproduction of microorganisms, even the variation rate of less than one millionth or even one billionth can rapidly develop into a considerable number of populations in a relatively short time, thus affecting the ecological environment Therefore, genetic stability is also an important index of safety evaluation 5 Genetic transfer ability Genetic transfer ability refers to the ability of animals to transfer genetic material from genetically modified microorganisms (especially genetically modified) to local non genetically modified homologous microorganisms and other organisms (including microorganisms, plants and animals) After obtaining the genetic material (complete transgene or part of it), there is a risk that it may evolve into new pests or enhance the harmfulness of pests For example, there are several research reports that PRV gene deficient vaccine strains can be genetically recombined with wild-type virulent strains, so that the virulence of the recombinant virus is enhanced, and the diagnostic marker genes are lost, which can further lead to the spread of virulent strains that can not be detected by standard serological tests, making it difficult to achieve the epidemic eradication plan Therefore, the possibility of genetic material transfer from antibiotic resistant genes and other exogenous genes (such as diagnostic marker genes, genes that enhance survival competitiveness or spread diffusion energy) in transgenic microorganisms to native microorganisms or other organisms in the natural environment and the possible impact on the ecological environment are also a problem of great concern to ecologists These two aspects constitute the concerns of scientists and the public about the safety of environmental release of genetically modified microorganisms for animals Compared with the long history of more than 100 years of development of conventional attenuated vaccine, the time of research and development of genetically modified microorganisms for animals is relatively short At present, the level of science and technology can not fully predict the performance of transgenes in the genetic background of recipient microorganisms, that is to say, we are still lack of enough understanding and foresight for the possible new combinations and new characters of transgenic microorganisms and their potential hazards However, as far as animal vaccines are concerned, there are safety problems in the traditional microbial vaccines Some inactivated vaccines can cause allergic reaction or even death of target animals due to endotoxin or ground allergen; most live attenuated vaccines have different degree of virulence problems in animals, and may have virulence back to strong in the environment; some vaccine strains have good safety to target animals, but have Hunyi pathogenicity to non target animals, etc At present, the prevalence of some major diseases has taken on a new look In the past, classical classical swine fever and classical Newcastle disease were relatively rare, while atypical swine fever and Newcastle disease occurred occasionally; diseases caused by Marek's disease virus super virulent strain and infectious bursal disease virus variant strain increased significantly; infectious bronchitis and inflammatory respiratory type were relatively rare, while renal disease type and adenogastric type were everywhere; E.coli not only caused diarrhea in young animals, but also made adult animals In the past, group C Streptococcus zooepidemicus was the main pathogen of Streptococcus suis Recently, it was found that group II Streptococcus had a great harm to pigs, infected human beings and caused death Although the new epidemic forms of these diseases are related to the epidemic law of the disease, improper use of vaccines and many other factors, they are related to the selective escape variation of wild pathogenic strains caused by the use of some live vaccines Biosafety control: since there may be safety problems after the release of genetically modified microorganisms, it is very necessary to control the biosafety of animals in order to prevent it The content of biosafety control after the release of genetically modified microorganism for animal includes the establishment of laws and regulations system, effective biosafety management, strict safety evaluation and practical safety control measures The establishment of laws and regulations system all over the world, especially the developed countries attach great importance to transgenic technology and its industrialization Many countries have formulated relevant laws, regulations and rules to strengthen management and control