Terry Etherton

Summary

Since the onset of the modern era of biotechnology in 1973, scientists have made impressive strides in developing new biotechnologies for agriculture (reviewed in Metabolic Modifiers, 1994; Etherton et al., 2003). Biotechnologies that enhance productivity and productive efficiency (feed consumed/unit of output) have been developed and approved for commercial use. Technologies that improve productive efficiency will benefit both producers and consumers because feed provision constitutes a major component (about 70%) of farm expenditures. Advances in biotechnology research have allowed impressive improvements to be made in diagnostic approaches, increasing microbial safety of food and improving animal health (reviewed in Etherton et al., 2003). The application of genomics, or the study of how genes (DNA) are organized and expressed, and bioinformatics in animal agriculture will provide new genetic markers for improved selection of all livestock species. The advent of techniques to propagate animals by nuclear transfer (cloning) offers many important applications to animal agriculture, including reproducing highly desired elite sires and dams. Animals selected for cloning will be of great value because of their increased genetic merit for increased food production, disease resistance, reproductive efficiency, or will be valued because they have been genetically modified to produce organs for transplantation or products with biomedical application (The National Academies, 2004). Biotechnology also offers considerable potential to animal agriculture as a means to reduce nutrients and odors from manure and volume of manure produced. Development and adoption of these biotechnologies will contribute to a more sustainable environment.

Advances in plant biotechnology also have had a huge positive impact on society. An impressive number of genetically modified (GM) plant varieties have been developed with improved qualities including enhanced tolerance of herbicides, and protection against viruses and insect pests, and beneficial modifications in nutrient profile (visit AGBIOS for additional information about GM crops, and a listing of approved biotech crops in the U.S). Presently, 74 different biotech crops have been approved for use in the U.S.

To reinforce the reality of how widely GM crops are being adopted it is useful to look at the database. These varieties have been adopted rapidly by American farmers, and the United States accounted for approximately 53% of the global area of transgenic crops in 2006 (James, 2006). Approximately 10.3 million farmers from 22 different countries planted GM crops in 2006 (James,2006). The 22 countries are Argentina, Australia, Brazil, Canada, China, Columbia, Czech Republic, France, Germany, Honduras, India, Iran, Mexico, Paraguay, Philippines, Portugal, Romania, Slovakia, South Africa, Spain, United States, and Uruguay. Another important measure of adoption is that acreage planted with GM crops in 2006 (250 million acres) is 13% higher than that planted in 2005 (James, 2006). This growth rate in global area planted in GM crops is impressive in that this is the tenth consecutive year that the increase has been in the double-digits!

The discovery and development of new animal and plant biotechnologies are part of a continuum leading to the commercialization of agricultural biotechnology products. In order to enter the marketplace, new animal biotechnologies are evaluated rigorously by the appropriate federal regulatory agencies to ensure efficacy, consumer safety, and animal health and well being (FDA, 2006). To benefit agriculture and society, products of biotechnology must be accepted by consumers. Central to consumer acceptance is the need to provide effective population-based education programs to enhance public understanding of the safety and benefits associated with technological advances enabled by agricultural biotechnology. Despite some of the most remarkable advances in biological research, a public discussion still continues about the need for, and safety of agricultural biotechnology that is fueled by misinformation campaigns funded by some anti-ag and anti-biotech activist groups. As we progress towards 2050, the scientific and agricultural communities must be more proactive in developing and delivering biotechnology and agriculture education campaigns for public and policy makers that clearly articulate the merits of current production practices used in animal agriculture. Moreover, the benefits of investing in discovery research that improves animal agriculture must be championed, and the return on this investment clearly communicated. The agricultural community is going to navigate a period over the next few decades during which we will likely witness growing challenges, especially increased regulatory oversight in addition to the misinformation campaigns funded by activist anti-ag groups. For the full benefits of agricultural biotechnology to be realized regulatory policy that evolves must be guided by the scientific evidence base, not vocal anti-ag activist groups.

Human Health: Uses of Biotechnology in Animal Agriculture to Decrease Morbidity and Mortality from Disease

Advances in recombinant DNA technology, animal embryology, immunology, and other disciplines give rise to the prospect that animals will become important sources of highly sophisticated biopharmaceuticals and biological products. A number of biopharmaceutical products are being developed in which the ultimate production system will be a genetically modified (GM) animal. In such instances, the gene for the desired molecule is designed and constructed to be expressed only in a specific tissue. Several companies focusing on these activities are targeting the production of specific animal proteins in milk (cattle, sheep, goats, pigs) and in eggs (poultry). These new approaches will allow for more economical production of certain pharmaceuticals that currently are expensive to produce. Biotechnological production methods thus may allow for a more widespread distribution and application of pharmaceuticals, including in developing countries. Another type of biotechnology under development involves using animals to produce donor organs for human transplant. There is a great shortage of transplant organs from human donors. Heart valves from pigs have been used for many years to replace heart valves in humans, and several private-sector companies and numerous university scientists are investigating ways in which to use biotechnology to develop pigs as a source of transplant organs. One key advantage of this approach is that it is possible that genetic engineering can be used to produce rejection-free organs. In each instance just described, a vital basic health need is being fulfilled by the use of animals, and no foreseeable alternatives exist.

Food Production: Uses of Biotechnology in Animal Production

Feeding Livestock

Health and safety are priorities in the development of new food and feed products, including those developed through biotechnological means. Evaluation by governmental regulatory agencies is required for each new biotech plant used for feed or food. Scientific studies evaluating feed components derived from GM plants have focused on beef cattle, swine, sheep, fish, lactating dairy cows, and broiler and layer chickens, and have included nutrient composition assessments, digestibility determinations, and animal performance measurements (Alewynse 2000; Beever and Kemp 2000; Faust 2002). Evaluations have shown uniformly that feed components derived from GM plants commercialized thus far are substantively equivalent in terms of nutrient composition and are similar in terms of nutrient digestibility and feeding value. Overall, feed components of GM plants result in growth rates and milk yields not different from those derived from non-genetically enhanced feed sources (Clark and Ipharraguerre 2001; Faust 2002; Flachowsky and Aulrich 2001). Studies have reported that when corn has been altered genetically for protection against the corn borer, under certain growing conditions GM plants can have lower mycotoxin contamination, resulting in safer feed for livestock (Munkvold et al., 1999).

Metabolic Modifiers

Advances in understanding the regulation of nutrient use in agricultural animals have led to the development of technologies referred to as metabolic modifiers. Metabolic modifiers are a group of compounds that modify animal metabolism in specific and directed ways. Metabolic modifiers have the overall effect of improving production, productive efficiency (weight gain or milk yield/unit of feed consumed), improving carcass composition (lean:fat ratio) in growing animals, increasing milk yield in lactating animals, and decreasing animal waste/production unit (NRC 1994).

Two classes of compounds have received major focus—somatotropins (STs) and ß-adrenergic agonists. The most commonly discussed ST is bovine somatotropin (bST), which has been commercially used since 1994 for administration to dairy cows to achieve increased milk yield, improve milk/feed, and decrease animal waste (Etherton and Bauman, 1998; Bauman, 1999).

Supplements of ß-adrenergic agonists to growing animals improve feed utilization and increase rate of weight gain, carcass leanness, and dressing percentage (National Research Council, 1994). Research has established the mode of action involves changes in endocrine and cellular mechanisms (National Research Council, 1994). The net effect is that these repartitioning agents improve productive efficiency by modifying specific metabolic signals in a coordinated manner to increase nutrient use for lean tissue. Ractopamine is the only ß-adrenergic agonist currently approved in the United States—in this instance, for finishing pigs; commercial use began in 2000.

Cloning

Cloning, a term originally used primarily in horticulture to describe asexually produced progeny, means to make a copy of an individual or, in cellular and molecular biology, groups of identical cells, and replicas of DNA and other molecules. For example, monozygotic twins are clones. Animal cloning in the late 1980s resulted from the transfer of nuclei from blastomeres of early cleavage-stage embryos into enucleated oocytes, and cloning of livestock and laboratory animals has resulted from transferring a nucleus from a somatic cell into an oocyte from which the nucleus has been removed (Wilmut et al., 1997; Westhusin et al., 2001).

Somatic cell nuclear transfer also can be used to produce embryonic stem cells, which are undifferentiated, and matched to the recipient for research and therapy that is independent of reproductive cloning of animals. The progeny from cloning using nuclei from either blastomeres or somatic cells are not exact replicas of an individual animal due to cytoplasmic inheritance of mitochondrial DNA from the donor egg, other cytoplasmic factors which may influence “reprogramming” of the genome of the transferred nucleus, and subsequent development of the cloned organism (Jaenisch and Wilmut, 2001).

Cloning by nuclear transfer from embryonic blastomeres (Willadsen, 1989) or from a differentiated cell of an adult (Wilmut et al., 1997; Polejaeva et al., 2000; Kuhholzer and Prather, 2000) requires that the introduced nucleus be reprogrammed by the cytoplasm of the egg and direct development of a new embryo, which is then transferred to a recipient mother for development to term. The offspring will be identical to their siblings and to the original donor animal in terms of their nuclear DNA, but will differ in their mitochondrial genes; variances in the manner nuclear genes are expressed are also possible. Although the word clone is descriptive for multiple approaches for cloning animals, in this article clone is used as a descriptor for somatic cell nuclear transfer.

On December 28, 2006, the Food and Drug Administration (FDA) released a draft risk assessment (RA) on whether cloning affects food safety or animal health, and whether food products from livestock should be sold for consumption. The draft, “A Risk-Based Approach to Evaluate Animal Clones and Their Progeny – Draft” concludes that “….the available data has not identified any food consumption risks or subtle hazards in healthy clones of cattle, swine, or goats. Thus, edible products from healthy clones that meet existing requirements for meat and milk in commerce pose no increased food consumption risk(s) relative to comparable products from sexually-derived animals.” Publication of the FDA Risk Assessment is an important next step in the process leading to the release the final regulatory guidelines that will allow food from cloned animals to enter the food system.

Conservation of the Environment

Meeting environmental challenges in agriculture is one of the major issues facing animal agriculture. Most swine and poultry manure is produced in confinement units for which the nearby land base often is insufficient to accommodate waste in an environmentally sound manner. Animal manure, especially swine and poultry manure, is high in nitrogen (N) (4.7 to 5.1%) and phosphorus (P) (1.6 to 3.0%), both of which can contribute to surface and groundwater pollution. In addition, ammonia and other nitrogenous and sulfurous gasses contribute to poor air quality and offensive odors. Several GM crops have been developed or are being developed to address the environmental issues related to N, P, and total manure excretion and odors (Etherton et al., 2003).

Phosphorus content in swine and poultry manure is high because these species consume diets consisting of cereal grains and oilseed meals in which most (60 to 80%) P is bound organically as phytic acid or phytate. Because of the lack of phytase in their digestive tract, nonruminants are unable to degrade phytate, and most P from these feed ingredients is excreted in the feces. In addition, relatively large amounts of inorganic P must be fed to pigs and poultry to meet their P requirements; consequently, fecal P excretion is increased further. Ruminants use phytate quite efficiently because of the abundance of phytase produced by rumen microorganisms.

It is exciting that opportunities are now available to decrease P content of manure (reviewed in Knowlton et al., 2004). These new strategies are based on a more accurate interpretation of P requirements (to not over-feed P), more precise diet formulation, and utilization of exogenous phytase or low-phytic acid grains in monogastric diets. The availability of microbial expression systems has made large amounts of the recombinant enzyme available for use in animal feed at relatively low costs (reviewed by Lei and Porres, 2003). Collectively, these strategies can lower P content of manure by 40-60% in pigs and poultry and 25 to 40% in ruminants (Knowlton et al., 2004).

A Look to the Future

The impressive growth in the science of biotechnology and the many products of biotechnology is one of the most impressive achievements in the history of science. Predicting what scientific discoveries will occur between the present and 2050 will, as always, be more than a bit challenging. Scientific advances will give us a better understanding of how genes work, and how they can be manipulated to achieve an optimal production outcome that benefits both the producer and consumer. Valuable animals that arise from conventional breeding or genetic manipulation can be propagated forever by cloning. I anticipate that we will be able to do large-scale modification of a large number of genes that will further enhance a variety of target production traits, production efficiency, and profitability.

Before we in the agricultural community get carried away anticipating scientific advances in biotechnology over the next 40 years, there are several key points that must be considered and addressed. First, funding for discovery and applied research in agriculture must be increased. Second, the discoveries made require a viable private sector to commercialize new products of biotechnology. This is becoming more challenging for a variety of reasons. The process of moving a product through the regulatory approval process is becoming more complex, costly and lengthy. This growing burden makes it challenging for private sector to recover their investment costs from product sales. This is particularly important for agricultural biotechnologies where the margins on products sold are lower than biomedical biotechnology products (using comparable scientific methods for production).

The last point pertains to the activist groups that are actively advocating use of biotechnology-derived products be halted. This is an ever-present reality. Many of these groups are well funded (visit Guidestar to see the IRS returns that all non-profits are required to place in the public domain), and attack animal agriculture on many fronts that range from animal welfare to biotechnology to environmental issues. It is simple to scare the public in 30 seconds; however, we can not educate them about science, agriculture, and biotechnology in 30 seconds. While it is a proven fact that biotechnology-derived (GM) crops are economically viable, environmentally sustainable, and are as safe as, if not safer, than their conventional counterparts, the debate over these agricultural biotechnologies and its applications continues. This is similar to the ongoing public discussion about rbST-free milk. My encouragement to animal agriculture is to passionately engage in developing and implementing consumer education programs that effectively frame the importance of animal agriculture and promote the need for and benefits of biotechnology in the barnyard.

References

Alewynse, M.G. 2000. Regulation of genetically modified plants in animal feed. FDA Vet. 15:1–2.

Bauman, D. E. 1999. Bovine somatotropin and lactation: From basic science to commercial application. Domest. Anim. Endocrinol. 17:101–116.

Beever, D.E. and C.F. Kemp. 2000. Safety issues associated with the DNA in animal feed derived from genetically modified crops. A review of scientific and regulatory procedures. Nutr. Abstr. Rev. B: Livestock Feeds Feeding. 70:175–182.

Clark, J.H. and I.R. Ipharraguerre. 2001. Livestock performance: Feeding biotech crops. J. Dairy. Sci. 84:E9–E18.

Cummins, J.M. 2001. Cytoplasmic inheritance and its implications for animal biotechnology. Theriogenology. 55:1381-1399.

Etherton, T.D. and D.E. Bauman. 1998. The biology of somatotropin in growth and lactation of domestic animals. Physiol. Rev. 78:745–761.

Etherton, T.D., D.E. Bauman, C.W. Beattie, R.D. Bremel, G.L. Cromwell, V. Kapur, G. Varner, M.B. Wheeler and M. Wiedmann. 2003. Biotechnology in Animal Agriculture: An Overview. CAST (Council for Agricultural Science and Technology) Issue Paper, No. 23.

Faust, M. 2002. New feeds from genetically modified plants: the U.S. approach to safety for animals and the food chain. Livestock Prod. Sci. 74:239–254.

FDA. 2006. A Risk-Based Approach to Evaluate Animal Clones and Their Progeny – DRAFT. http://www.fda.gov/cvm/CloneRiskAssessment.htm

Flachowsky, G. and K. Aulrich. 2001. Nutritional assessment of feeds from genetically modified organism. J. Anim. Feed. Sci. 10:181–194.

James, C. 2006. Global Status of Commercialized Biotech/GM Crops: 2006. International Service for the Acquisition of Agri-biotech Applications. Brief Number 35-2006. ISAAA, Ithaca, New York.

Jaenish, R. and I. Wilmut. 2001. Developmental biology. Don’t clone humans! Science. 291:2552.

Knowlton, K.F., J.S. Radcliffe, C.L. Novak and D.A. Emmerson. 2004. Animal management to reduce phosphorus losses to the environment. J. Anim. Sci. 82(E. Suppl.):E173-E195.

Kuhholzer, B. and R.S. Prather. 2000. Advances in livestock nuclear transfer. Proc Soc Exp Biol Med. 224:240-245.

Lee, X.G. and J.M. Porres. 2003. Phytase enzymology, applications, and biotechnology. Biotechol. Lett. 25:1787-1794.

Metabolic Modifiers: Effects on Nutrient Requirements of Food-Producing Animals. 1994. T.D. Etherton (Ed.). Board on Agriculture, National Research Council, National Academy of Science Press, Washington, D.C.

Munkvold, G.P., R.L. Hellmich, and W.B. Showers. 1999. Reduced fusarium ear rot and symptomless infection in kernels of maize genetically engineered for European corn borer resistance. Phytopathol. 87:1071–1077.

National Research Council (NRC). 1994. Metabolic Modifiers: Effects on the Nutrient Requirements of Food-producing Animals. The National Academy Press. Washington, D.C.

Polegaeva, I.A., S.H. Chen, T.D. Vaught, R.L. Page, J. Mullins, S. Ball, Y. Dai, J. Boone, S. Walker, D.L. Ayares, A. Colman and K.H. Campbell. 2000. Cloned pigs produced by nuclear transfer from adult somatic cells. Nature. 407:86-90.

The National Academies. 2004. Safety of Genetically Engineered Foods. Approaches to Assessing Unintended Health Effects. Institute of Medicine and National Research Council of
The National Academies. The National Academy Press. Washington, D.C.

Westhusin. M.E., C.R. Long, T. Shin, J.R. Hill, C.R. Looney, J.H. Pryor and J.A. Piedrahita. 2001. Cloning to reproduce desired genotypes. Theriogenology. 55:35-49.

Wilmut I., A.E. Schnieke, J. McWhir, A.J. Kind and K.H. Campbell. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature. 385:810-813.

Willadsen, S.M. 1989. Cloning of sheep and cow embryos. Genome. 31:956-962.