Animal biotechnology is the application of scientific and engineering principles to the processing or production of materials by animals or aquatic species to provide goods and services (NRC 2003). Examples of animal biotechnology include generation of transgenic animals or transgenic fish (animals or fish with one or more genes introduced by human intervention), using gene knockout technology to generate animals in which a specific gene has been inactivated, production of nearly identical animals by somatic cell nuclear transfer (also referred to as clones), or production of infertile aquatic species.
Since the early 1980s, methods have been developed and refined to generate transgenic animals or transgenic aquatic species. For example, transgenic livestock and transgenic aquatic species have been generated with increased growth rates, enhanced lean muscle mass, enhanced resistance to disease or improved use of dietary phosphorous to lessen the environmental impacts of animal manure. Transgenic poultry, swine, goats, and cattle also have been produced that generate large quantities of human proteins in eggs, milk, blood, or urine, with the goal of using these products as human pharmaceuticals. Examples of human pharmaceutical proteins include enzymes, clotting factors, albumin, and antibodies. The major factor limiting widespread use of transgenic animals in agricultural production systems is the relatively inefficient rate (success rate less than 10 percent) of production of transgenic animals. CSREES has supported research projects to generate transgenic animals or transgenic aquatic species with enhanced production or health traits.
Gene Knockout Technology
Animal biotechnology also can knock out or inactivate a specific gene. Knockout technology creates a possible source of replacement organs for humans. The process of transplanting cells, tissues, or organs from one species to another is referred to as “xenotransplantation.” Currently, the pig is the major animal being considered as a xenotransplant donor to humans. Unfortunately, pig cells and human cells are not immunologically compatible. Pig cells express a carbohydrate epitope (alpha1, 3 galactose) on their surface that is not normally found on human cells. Humans will generate antibodies to this epitope, which will result in acute rejection of the xenograft. Genetic engineering is used to knock out or inactivate the pig gene (alpha1, 3 galactosyl transferase) that attaches this carbohydrate epitope on pig cells. Other examples of knockout technology in animals include inactivation of the prion-related peptide (PRP) gene that may generate animals resistant to diseases associated with prions (bovine spongiform encephalopathy [BSE], Creutzfeldt-Jakob Disease [CJD], scrapie, etc.). Most of the funding for these types of projects is conducted by private companies or in academic laboratories supported by the National Institutes of Health. Research projects designed to provide basic information regarding mechanisms associated with gene knockout technology are supported by CSREES.
Somatic Cell Nuclear Transfer
Another application of animal biotechnology is the use of somatic cell nuclear transfer to produce multiple copies of animals that are nearly identical copies of other animals (transgenic animals, genetically superior animals, or animals that produce high quantities of milk or have some other desirable trait, etc.). This process has been referred to as cloning. To date, somatic cell nuclear transfer has been used to clone cattle, sheep, pigs, goats, horses, mules, cats, rats, and mice. The technique involves culturing somatic cells from an appropriate tissue (fibroblasts) from the animal to be cloned. Nuclei from the cultured somatic cells are then microinjected into an enucleated oocyte obtained from another individual of the same or a closely related species. Through a process that is not yet understood, the nucleus from the somatic cell is reprogrammed to a pattern of gene expression suitable for directing normal development of the embryo. After further culture and development in vitro, the embryos are transferred to a recipient female and ultimately will result in the birth of live offspring. The success rate for propagating animals by nuclear transfer is often less than 10 percent and depends on many factors, including the species, source of the recipient ova, cell type of the donor nuclei, treatment of donor cells prior to nuclear transfer, the techniques employed for nuclear transfer, etc. CSREES has supported research projects to obtain a better understanding of the basic cellular mechanisms associated with nuclear reprogramming.
Production of Infertile Aquatic Species. In aquaculture production systems, some species are not indigenous to a given area and can pose an ecological risk to native species should the foreign species escape confinement and enter the natural ecosystem. Generation of large populations of sterile fish or mollusks is one potential solution to this problem. Techniques have been developed to alter the chromosome complement to render individual fish and mollusks infertile. For example, triploid individuals (with three, instead of two, sets of chromosomes) have been generated by using various procedures to interfere with the final step in meiosis (extrusion of the second polar body). Timed application of high or low temperatures, various chemicals, or high hydrostatic pressure to newly fertilized eggs has been effective in producing triploid individuals. At a later time, the first cell division of the zygote can be suppressed to produce a fertile tetraploid individual (four sets of chromosomes). Tetraploids can then be mated with normal diploids to produce large numbers of infertile triploids. Unfortunately, in a commercial production system, it is often difficult to obtain sterilization of 100 percent of the individuals; thus, alternative methods are needed to ensure reproductive confinement of transgenic fish. Another technique that is being developed for finfish is to farm monosex fish stocks. Monosex populations can be produced by gender reversal and progeny testing to identify XX males for producing all female stocks or YY males for producing all male stocks. CSREES has supported research projects to alter the chromosome content or produce monosex populations of genetically engineered fish or mollusks.
As with any new technology, animal biotechnology faces a variety of uncertainties, safety issues and potential risks. For example, concerns have been raised regarding: the use of unnecessary genes in constructs used to generate transgenic animals, the use of vectors with the potential to be transferred or to otherwise contribute sequences to other organisms, the potential effects of genetically modified animals on the environment, the effects of the biotechnology on the welfare of the animal, and potential human health and food safety concerns for meat or animal products derived from animal biotechnology. Before animal biotechnology will be used widely by animal agriculture production systems, additional research will be needed to determine if the benefits of animal biotechnology outweigh these potential risks. The USDA Biotechnology Risk Assessment Grants program supports environmental risk assessment research projects on genetically engineered animals. In addition, the NRI Animal Protection program supports research projects to determine the effects of genetic modification on the health and well-being of the animal.
Advances in animal biotechnology have been facilitated by recent progress in sequencing and analyzing animal genomes, identification of molecular markers (microsatellites, expressed sequence tags [ESTs], quantitative trait loci [QTLs], etc.) and a better understanding of the mechanisms that regulate gene expression.