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Basic Paper Conference: Forum 6: Biotechnology: Basic Paper Bio- and Gene Technology in Farm Animals: Perspectives for Animal Breeding in the New Millennium The breeding of livestock species has a long tradition in human history. It began with domestication, continued by selected multiplication of useful populations or individuals and culminated in a scientifically based breeding after the second world war. The latter included already artificial insemination as a crucial biotechnological procedure without which the progress in animal performance would not have been achieved. During the eighties of the twentieth century, embryo transfer and cryopreservation of embryos have been added to the arsenal of breeding technologies. However, the current systems still have three major disadvantages. 1. The genetic progress is only 1 to 3% per year and thus very slow. 2. It is not possible to separate desired traits from unwanted traits. 3. A targeted transfer of genetic information between species is not possible. It is anticipated that the merging of reproductive technologies with the new molecular tools will overcome these limitations and will open a completely new horizon in animal breeding. The reproductive biology side of modern biotechnology comprises artificial insemination (AI), estrus synchronization, synchronization of parturition, embryo transfer (ET), cryopreservation of gametes and embryos, in vitro production of embryos, generation of identical multiplets (twinning and cloning via nuclear transfer), sex determination. The molecular biological side includes genome analysis (genome mapping, single gene analysis, interaction between genes), application of recombinant substances (e.g. bovine and porcine somatotropin, phytase), molecular biological diagnostics to identify genetic disorders, proof of descent, identity or infection and finally gene transfer. Biotechnology in livestock possesses a distinct interdisciplinary character and harbours elements from anatomy, gynaecology, endocri-nology, physiology, andrology, ultrasound technology, biochemistry, cell biology as well as molecular biology. The further development of bio- and gene technology with the final goal to achieve field application is an important tool to cope with future challenges to livestock production. Some of these challenges are: quantitative and qualitative increases of food production, cost limitation or reduction, protection of the environment, diversification of production, maintenance of genetic diversity, as well as the best possible standard of animal welfare. Worldwide, approximately 9 to 10% of the earth surface is usable for agriculture. In light of an ever increasing population (projected are approximately 7.8 billion people in the year 2010), it is clear that the output of agriculture has to be further increased in a very significant manner. It is estimated that agriculture production has to be tripled over the next 40 years to cope with the projected increase of the world population. Meanwhile it is well known that the increase in population growth can only be stopped when a certain degree of wealth and health care can be provided. It is also known that this is correlated with an increase of high quality food consumption which comprises about 25-30% animal products. With the increase in the living standard in the Peoples Republic of China the consumption of meat increased yearly by 10% or 3 Mio. tons over the last 3 to 4 years. Most prominent examples for biotechnological procedures with profound effects on future animal breeding are gene transfer and nuclear transfer. Gene transfer means the introduction of foreign protein coding DNA-sequences into the genome of a given recipient with the final goal of an active contribution of the foreign gene to protein synthesis of the recipient organism. Animals with integration of a foreign gene into their genome are called �transgenic�. Normally DNA-constructs are employed with include natural or artificial combinations of regulatory (promoter, enhancer) and protein coding (structural gene) DNA-sequences. The vast majority of transgenic livestock produced so far has been generated via microinjection of a DNA-solution into pronuclei of early fertilized oocytes (= zygotes). The efficiency of this procedure is low and reaches only 1-4% of the born offspring. Additionally, integration occurs at random, frequently leading to unpredictable variation in expression of the foreign gene. Nevertheless, this procedure has been used very successful for biomedical purposes. Today, transgenic sheep, goat and cattle are already available that produce high amounts of pharmaceutical proteins in their milk from which the product can be purified, isolated and used in clinical tests. There are several products (e.g. human antithrombin III, glucosidase, ?1-antitrypsin, tissue plasminogen activator) that are already in an advanced phase of clinical testing. It is anticipated that the first product from the mammary gland of a transgenic animal will be on the market within the next 2 to 3 years. Similarly, transgenic pigs expressing human complement inhibitory genes have been generated to overcome the hyperacute rejection response observed when discordant organs are transferred (= xenotransplantation). The availability of suitable porcine organs is currently considered the only solution to overcome the worldwide shortage of appropriate human organs. When organs from transgenic pigs were transferred into primates already extended survival of the recipients (> 70 days) could be achieved. The risk of a potential infection of the recipients with porcine endogenous retroviruses (PERVs) has recently been shown to be a minor one. It is expected that clinical trials with human patients will be performed in the near future. In contrast to the well advanced technology in biomedicine, transgenic animals with agricultural traits in its narrower sense are not that far developed mainly due to a lack of sufficient genetic knowledge on agriculturally relevant traits. The limitations of current gene transfer methodology are expected to be overcome by an improved nuclear transfer protocol. Since it has been shown that somatic cells can be successfully reprogrammed by transferring them to enucleated oocytes, followed by fusion of both components and subsequent development to an early embryo and even normal offspring, the hopes for significant improvements in genetic engineering of animals are very well founded. Appropriate cells or cell lines can be genetically modified and successfully used in nuclear transfer. Transfection still results in random integration of the transgene. However, this procedure allows selection of those cells from a given population that express the gene as desired without negative side effects. This approach moves already considerable parts of the testing from the barn into the laboratory. The ultimate step towards improving the generation of transgenic animals will be the application of homologous recombination which allows insertion of a foreign gene at a predetermined chromosomal site. This technology is well described in mice where totipotent permanent embryonic stem cell lines are available, which were originally thought to be an essential prerequisite for homologous recombination. However, recently it has been shown that somatic cells can efficiently be transformed by techniques of homologous recombination. These cells can be employed in nuclear transfer and have been shown to generate normal and healthy offspring. The integration of a foreign gene at a predetermined chromosomal site allows a significantly better control of transgene expression. With the increasing knowledge on the genomic maps in livestock, it will be possible to apply this technology to a variety of traits. The efforts towards mapping genes in livestock are much less advanced than in the human (human genome project). However, livestock will benefit from the relatively high degree of genomic homology between human and livestock. This will facilitate genome mapping in livestock species. With the availability of such technology in the field, diversification (e.g. diversified milk production: casein enriched milk for curd and/or cheese production, hypoallergic milk, lactose-free milk, etc.) in various production areas will be possible and increases in efficiency can be achieved that would not be possible with conventional breeding technology. In light of the above mentioned challenges, e.g. lack of resources, damage of the environment, cost limitations, etc., the positive application areas of bio- and gene technologies require further intensive research to achieve the level of commercial exploitation as soon as possible. This has to be done in accordance with the existing high animal welfare and ethical standards. Potential effects of biotechnology on social and economic conditions should be discussed prior to field application. Progress in animal breeding has been an integral part of human culture and progress in bio- and gene technology will be an undispensable basis for tackling future problems of mankind. Address of author: Prof. Dr. H. Niemann Dept. of Biotechnology Institut f�r Tierzucht und Tierverhalten (FAL) Mariensee 31535 Neustadt, Germany |