The U.S. Food and Drug Administration (FDA) released two recent documents that renewed public and congressional interest in animal biotechnology in general and animal cloning in particular. On January 15, 2009, the agency released final guidance representing its current thinking on the regulation of genetically engineered (GE) animals for food or drugs. FDA did so under its existing statutory authority and regulations. A year earlier, on January 15, 2008, FDA had unveiled its final risk assessment and industry guidance on the safety of milk and meat from cloned animals and their offspring. FDA found that, generally, meat and milk products from cattle, pigs, and goats are as safe as products from their non-cloned counterparts. Still, some in the United States remain concerned about the safety and other impacts of GE animals and of animal cloning, and they continue to advocate a cautious approach to commercialization of such products. Outside of the United States, animal biotechnology, including both GE and cloning, is the focus of ongoing regulatory, policy and scientific discussions within the European Union (EU) as well as within the international organization for animal health, known by its French acronym, the OIE. (Cloning by itself is not considered to be genetic engineering; see discussion later in this report.) Biotechnology is a broadly defined term of relatively recent origin describing the range of modern knowledge, applications, and techniques underlying advances in many fields, notably health care and agriculture. Animal biotechnology has been defined as "that set of techniques by which living creatures are modified for the benefit of humans and other animals." By its very nature, agricultural development is the history of humans modifying plants and animals to maximize desirable traits. For example, domestication and selective breeding of animals date back many thousands of years. Artificial insemination of livestock, notably dairy cattle, is a more recent technology, first finding wide commercial acceptance in the 1950s. Discovery of the genetic code in the 1950s gave birth to modern techniques of biotechnology. One of the first commercial products of this new biotechnology in animal agriculture was bovine somatotropin (bST), a naturally occurring metabolic modifier that is now being manufactured in larger quantities through the use of recombinant DNA technology. Manufactured bST came onto the market in 1994 and is now administered to as many as half of all U.S. dairy cattle to increase per-cow milk output. Although bST is being used commercially in approximately 20 countries, it is banned in the European Union (EU). The first U.S. approval of a commercial product from a GE animal is for the drug ATryn, an anticoagulant agent being produced in the milk of transgenic goats. FDA announced its approval on February 6, 2009. The goats were genetically engineered by introducing a segment of DNA into their genes that coded for the goat to produce human antithrombin in its milk. Antithrombin is a naturally occurring protein in healthy humans that helps keep blood from clotting in blood vessels. Other developments include pigs that have been engineered for increased sow milk output to produce faster-growing piglets. Chinese researchers announced in April 2011 that they had produced a herd of dairy cattle whose milk contains human breast milk proteins (lysozyme, lactoferrin, and alpha-lactalbumin). The researchers used cloning technology to introduce human genes into the DNA of Holstein dairy cows before the genetically modified embryos were implanted into surrogate cows. Cloned cattle also have been developed to resist mastitis, an infectious disease of the udder. A genetically engineered salmon—AquAdvantage salmon—with enhanced growth characteristics is currently under review by FDA for commercialization. If approved, it would be the first GE animal approved for human consumption. The company that developed the salmon, AquaBounty Technologies, Inc., has artificially combined growth hormone genes from an unrelated Pacific salmon with DNA from the anti-freeze genes of an eelpout. This modification causes production of growth hormone year-round, creating a fish the company claims grows at twice the normal rate. Output traits such as drugs recovered from animal milk ("pharming"), milk that lacks allergenic proteins, and animal organs for human transplant (xenotransplantation) that resist rejection are other contemporary objectives of animal biotechnology research. In March 2006, researchers at the University of Missouri announced the creation of transgenic pigs whose tissue contains omega-3 fatty acids. The consumption of omega-3 fatty acids, found primarily in fish, has been linked to lowered incidence of heart disease in humans. Similar research is also under way to produce omega-3 fatty acids in cow's milk and in chicken eggs. This report describes several scientifically emerging animal biotechnologies that are raising a variety of questions concerning risks to humans, animals, and the environment, as well as ethical concerns. The report examines applications of the technologies and discusses major issues that may arise. Consumers, agricultural producers, the biotechnology industry, and federal regulatory bodies are debating the relative costs and benefits of these technologies. As technologies move toward commercialization, Congress is being asked to examine these issues and possibly to refine the current federal regulatory structure governing the technologies and their agricultural products. Given the breadth of the term "animal biotechnology," one might reasonably define it to include thousands of years of humans selectively breeding animals: observing desirable animal traits and attempting to breed those traits into successive lines of animals. One of the first modern forms of assisted reproductive technology (ART) was artificial insemination (AI). AI has been long established as a technological advance in traditional selective breeding and an important adjunct to the development of modern industrial animal production, especially in dairy and poultry. AI was adopted by producers and accepted by the public with virtually no controversy. For example, more than 70% of all U.S.-bred Holstein cows, by far the most widely used milk producers, are artificially inseminated. Estrus synchronization, which improves the efficiency of AI by more accurately controlling when a female is in heat, is also an important animal biotechnology. With the development in the 1970s and patenting in the 1980s of recombinant DNA techniques, and the subsequent analysis of genes, their resulting proteins, and the role played by the proteins in animal biochemical processes (functional genomics), modern biotechnology is increasingly equipped with a set of sophisticated tools holding the promise of transforming the selective breeding of animals. The range of new techniques and technologies could transform animal biotechnology in ways that plant biotechnology was transformed in the 1980s and 1990s. Modern animal biotechnology is developing against the background of public experience with plant biotechnology, and controversy over the technologies may be a continuing feature of animal biotechnology development, not least because of the closer connection between humans and some animals and the belief that techniques developed for animals are only a step away from application to humans. Some of the better known animal biotechnologies follow. A number of them are types of assisted reproductive technology (ART). After AI and estrus synchronization, embryo transfer (ET) is the third-most commonly used animal biotechnology technique. In ET, a donor cow of superior breeding is chemically induced to superovulate. The eggs are then fertilized within the donor, the embryo develops and is then removed and implanted in a recipient cow. Between removal and implantation, embryos may be frozen for safekeeping. Because of the relatively high costs, ET is used mostly within registered cowherds. A prominent area of contemporary animal biotechnology research is the development of transgenic animals through genetic engineering (GE) technology. Transgenic animals are produced by introducing an isolated DNA fragment into an embryo so that the resulting animal will express a desired trait. Transgenic animals may be generated by the introduction of foreign DNA obtained through animals of the same species, animals of different species, microbes, humans, cells, and in vitro nucleic acid synthesis. The only currently routine use of transgenic animals, primarily mice, is in the area of human disease research. The anti-clotting agent in goat milk is the first such application to be approved by FDA (March 2009). As noted above, a herd of GE dairy cattle has been created that produces human breast milk proteins in the cow's milk. That innovation could be 10 years or more away from any commercialization efforts. Potential agricultural applications from genetically engineering animals could include improved feed use and faster growth; more resistance to disease; meat that is leaner or that has more of some other desirable quality; and possibly even animal waste that is more environmentally benign. Table 1 provides examples of various objectives of animal biotechnology involving genetic modification. With in vitro fertilization (IVF), a technician removes unfertilized eggs (oocytes) from the donor cow's ovaries, usually recovering 6-8 useable oocytes. The oocytes mature in an incubator and are fertilized with sperm. The resulting zygotes incubate and develop in the laboratory before being placed into the recipient cow. While IVF can produce many fertilized embryos, the added expense of ET makes the procedure prohibitive in most cases. The dairy industry prefers heifers and the beef industry prefers bulls. Embryo sexing methods in cattle have been developed using a bovine Y-chromosome probe. Technicians remove a few cells from the embryo and assess the DNA in these cells for the presence of a Y-chromosome. Presence of a Y-chromosome determines the embryo is male. Research is also developing in sperm sexing technology. Cloning, discussed at greater length below, is a biotechnology technique developing rapidly and with significant public controversy. Most people think of cloning as the creation of an organism that is genetically identical to another one. However, scientists use the term more broadly, to refer to production not only of such organisms but also of genetically identical cells, and to replication of DNA and other molecules. It also refers to a form of reproduction found naturally in many single-celled organisms, as well as plants and animals.