Genetic Engineering and Cloning May Improve Milk, Livestock Production

- aE Transgenic sheep, goats, pigs and cattle are now routinely made, although efficiency is low and costs are high. Conventionally bred sheep are herded near Cholame. Genetic engineering and cloning may improve milk, livestock production

James D. Murray il Gary B. Anderson

In the past, procedures such as Within the next few decades, how- raditionally, genetic improve- artificial insemination and embryo ever, genetically engineered dairy Tment of livestock has been transfer have been used in the ge- cows could become available. achieved by applying the principles netic manipulation of livestock. Cloning may also be used to du- of quantitative genetics and animal Advances in gene and quantitative- plicate animals with traits that are breeding. Milk production in dairy trait mapping will enhance these difficult to capture through tradi- cattle, for example, has increased 100 pounds of milk per cow per traditional animal-breeding ap- tional breeding practices. By year due to genetic selection, aug- proaches to improve farm ani- 2025, cloning and breeding of elite mented by artificial insemination. mals. By genetically engineering animals could be carried out by Advances in gene and quantitative- livestock, scientists hope to pro- companies comparable to those trait mapping in the last decade will duce animals with altered traits that now comprise the artificial in- ensure that traditional animal- such as disease resistance, wool semination industry, which se- breeding approaches, coupled with growth, body growth and milk lects and breeds top dairy stock. newer techniques for marker- composition. Laboratories world- The acceptance of genetically assisted selection, will be effective wide have produced transgenic engineered animals by industry in providing continued genetic im- pigs, sheep, goats and cattle, but will depend on its economic ben- provement of livestock. The advent currently the efficiency of produc- efits and whether consumers are of modern biotechnology also prq- ing the animals remains low and prepared to buy the resulting vides new avenues for genetic im- the procedure is expensive. products. provement in production animals.

CALIFORNIA AGRICULTURE, JULY-AUGUST 2000 57 In the broadest sense, biotechnol- producing genetically engineered or passed to a transgenic animal's prog- ogy includes procedures commonly transgenic animals, resulting in a para- eny requires that the original used in animal production, such as ar- digm shift in modern biological re- transgenic animal reach sexual matu- tificial insemination and embryo trans- search (Gordon et al. 1980). Initial suc- rity and then complete at least one fer - both of which have successfully cesses with transgenic mice were gestation period. This could take sev- increased the rate of genetic improve- subsequently extended to agricultural eral years in some species. ment in species. During the past 10 to species. Laboratories worldwide have Microinjection of DNA into the pro- 15 years, however, the term biotech- produced transgenic pigs, sheep, goats nuclei of recently fertilized ova is the nology has come to be associated more and cattle (Pinkert and Murray 1999). most common technique used to pro- with molecular-based technologies, However, the efficiency of producing duce genetically engineered livestock, such as gene cloning and genetic transgenic ruminants and pigs re- but on average fewer than 2% of mi- engineering. mains low, the costs are high and the croinjected embryos yield transgenic The initial development of tech- time required to produce and charac- individuals. Furthermore, pronuclear niques for cloning and manipulating terize transgenic livestock is long microinjection has allowed only the gene sequences in the 1970s was fol- (Wall et al. 1992). For example, deter- random integration of a transgene into lowed 10 years later by techniques for mination that the introduced gene is the animal genome. Since 1980, scientists have made continual advances in the efficiency of producing embryos from farm animals in the laboratory, called in uitro matu- ration and fertilization. These techniques, combined with improved con- ditions for embryo culture and cryopreservation and increased expe- rience and sophistication in the production and manipulation of embryos, culminated in the cloning of an adult sheep, "Dolly," by Scottish scientists in 1997 (Wilmut et al. 1997). Advances in animal cloning procedures, beginning with transgenic do- nor cells, have also resulted in the production of transgenic sheep, goats and cattle. Although today's overall efficiency appears to be comparable to that of pronuclear microinjection, cloning to produce transgenic livestock will allow the insertion of DNA sequences - as embryonic stem cells do in mice - creating the opportunity to alter or remove a specific gene (fig. 1). With continued scientific improvements, the production of transgenic livestock through cloning could eventually be more efficient than pronuclear microinjection. Modern biotechnology can be used to improve the genetic merit of livestock by two routes: transferring novel genetic material via genetic engineering or accel- erating the dissemination of desirable traits via the cloning of selected individual animals. Cloning and genetic improvement The successful cloning of an adult sheep (Wilmut et al. 1997) captured

58 CALIFORNIA AGRICULTURE, VOLUME 54. NUMBER 4 the imagination of both the scientific community and the rest of the world. Dolly - the sheep cloned from a cultured mammary gland cell of a 6-year- old ewe long since dead - made the cover of most major news and scientific magazines and became the subject of global commentary and debate. Lost in the debate was a primary reason be- hind the investigators‘ experiments: the identification of cell types that could be genetically manipulated in the laboratory and subsequently used to generate a transgenic animal. Developments in cloning have taken two forms since Dolly’s birth: demonstrations of the practical uses of cloning to produce transgenic animals, and the expansion of the species and types of cells that can be used as nuclear donors in successful cloning. Transgenic fetal fibroblasts - isolated and engineered from connective tissue cells - have been used to clone transgenic lambs, calves and goat kids. Successful cloning from adult cells has been expanded to include various cell types in cattle and laboratory mice. The potential to clone adult animals creates entirely new dimensions for animal agriculture. A desirable and unique specimen can be precisely re- produced, capturing traits that are difficult to develop through traditional breeding practices. For example, a dairy cow that produces milk with unusually high milk protein content Fig. 1. Transgenic farm animals are produced by direct microinjection of DNA into young embryos and by cloning from transgenic somatic cells. Microinjection proce- (which is important for making dures use recently fertilized eggs, which for some species can be obtained from in vitro cheese), or with an unusually low per- fertilization procedures, before the first cell division. If the foreign DNA becomes inte- centage of saturated fat (which has hu- grated into the embryonic genome at the one-cell stage, as the embryo develops all of man health benefits), could be cloned. its cells will contain the transgene. The offspring that is born after transfer of the embryo to the reproductive tract of a recipient female will be transgenic. Alternatively, so- Selective breeding from an individual matic cells can be collected from an animal, cultured in the laboratory, and exposed to animal is not always successful, but foreign DNA. Some cells will become transgenic, and these cells can be selected for use selective breeding from a nucleus core as nuclear donors in nuclear-transfer procedures. The resulting nuclear-transfer embryo herd of cloned animals is more likely will be transgenic, as will the offspring born after embryo transfer and term development in the reproductive tract of a recipient female. to succeed. An example of the power of cloning is the preservation of the last surviv- on genetic improvement, but potential the use of embryo transfer technology. ing cow of the Australia’s Enderby Is- impacts could be considerable for in- The ability to clone genetically elite land cattle breed. Cloning of this female tensively managed systems such as the females, while possibly increasing the and use of available cryopreserved se- dairy industry. Early in the 21st cen- level of inbreeding, also increases the men to breed the surviving clones could tury, cloning could be used to dupli- intensity of genetic selection. By 2025, provide a second chance to resurrect a cate the top-producing dairy cows. Ar- cloning and breeding of these cloned breed that otherwise would have tificial insemination eliminates the animals could be carried out by compa- disappeared. need to clone elite bulls, but at present nies comparable to the current artificial- We can only speculate about what each elite cow can produce only a lim- insemination industry, which is re- impact cloning technology will have ited number of offspring, even with sponsible for selection and breeding

CALIFORNIA AGRICULTURE. JULY-AUGUST 2000 59 A recently fertilized bovine embryo (zygote) is microinjectedto introduce a DNA solution into its genetic material. Microinjection of zygotes is currently the most common method to produce transgenic animals. This transgenic goat has a transgene that codes for a human protein under the control of a promoter region that targets expression specifically to the mammary gland. The.human protein is secreted in the goat’s milk but nowhere else in the animal. of the top dairy stock. The swine in- unregulated levels of circulating GH, mammary gland of farm animals ei- dustry could undertake a similar strat- they also suffered a number of compli- ther has focused on studying the pro- egy for the expansion of the cloned cations, such as joint problems, indi- moter function or on the production lines of top breeding sows. cating the need for tight control of hor- and recovery of biologically impor- mone secretion. tant, active proteins for use as pharma- Livestock with improved traits Recently, two research groups re- ceuticals (Maga and Murray 1995). During the 15 years since the first ported preliminary data on the develop- Several private companies have transgenic farm animals were pro- ment of GH and IGF-I transgenic pigs produced transgenic cows, sheep, duced, the rationale for genetic engi- with enhanced growth-performance goats and pigs, targeting transgenic neering of livestock for agricultural traits (Nottle et al. 1999; Purse1 et al. expression to the mammary gland purposes has been to produce animals 1999). In both experiments, desirable with the aim of isolating high-value with altered traits such as disease re- effects on growth and body composi- pharmaceutical proteins from milk. sistance, wool growth, body growth or tion traits were achieved without ap- But the use of transgenesis for agricul- milk composition. In most instances, parent abnormalities, suggesting that tural purposes, such as to alter the the objective has been either to alter someday useful animals could become properties and composition of milk traits for improved production effi- available to swine breeders. Poten- and change the functional properties ciency or to alter the properties of the tially useful GH-transgenic fish also of the milk protein system, is also pos- animal product, such as wool or milk, have been produced, but biological sible by adding a new gene or altering and increase the range of manufactur- containment of the transgene is of an existing gene. ing options. great concern in species with existing We have produced transgenic mice Gene constructs - designed to ex- wild fish populations. that express human lysozyme or a press directly or indirectly various Milk protein genes have been modified bovine casein (a protein used growth factors and alter body compo- cloned from a variety of mammals. in cheese-making and for some indus- sition - constitute the largest class of The promoter elements from certain trial purposes) in the milk. As a result, transgenes transferred into livestock milk-protein genes from one or more we have measured alterations in the species. The majority of these species have been used to facilitate ex- physical and functional properties of transgenes expressed growth hormone pression of transgenes in the mam- the mouse’s milk protein system, in- (GH), although other constructs based mary glands of mice, sheep, goats, cluding decreased micelle size and in- on GH release and insulin-like growth cattle, rabbits and pigs (Murray and creased gel strength. The production factor-I (IGF-I) also have been used. In Maga 1999). These transgenes are de- of human lysozyme in milk of general, pigs and sheep expressing velopmentally correct, but their levels transgenic mice also increased the an- these constructs were leaner and more of expression can vary. Research on timicrobial properties of the milk, feed-efficient. But as a result of high, targeting transgene expression to the which in cows could reduce infections

60 CALIFORNIA AGRICULTURE, VOLUME 54, NUMBER 4 Within 20 years, transgenic and cloned animals could become useful in production agriculture. For these technologies to be commer- cialized, issues such as the integration of transgenes into breeding populations, genetic diversity and inbreeding, and industry and consumer acceptance must be addressed. in the mammary gland and perhaps possible. Richardson and colleagues et al. 1996) or human lysozyme (Maga eliminate undesirable pathogens in proposed specific alterations in the et al. 1997) to the milk protein system. the gut of humans who consume the properties of milk that might be Ongoing research, supported in milk. acKkved by ovexexpressing, deleting part by the indnstry's CaYifomia Dairy or adding back a mutated form of Research Foundation, is exploring po- Alternative scenarios most major milk protein genes tential uses of transgenic technology in Two scenarios demonstrate how ge- (Jimenez-Flores and Richardson 1988; the dairy industry. We expect geneti- netic engineering can be applied to im- Yom and Richardson 1993). For ex- cally engineered dairy cows to become prove livestock. The first involves al- ample, adding extra copies of the available within two decades, includ- tering milk to improve functionality casein gene to overexpress casein

and human health. In the second sce- could increase the thermal stability of ~~ nario, genetic engineering is used to milk, reducing protein breakdown reduce environmental pollution stem- during manufacturing. We expect genetically ming from animal agriculture and A more complex proposal would be aquaculture. Other useful applications to alter a casein gene at a specific site engineered dairy cows to are possible; perhaps diseases such as (called site-directed mutagenesis) become available within scrapie and "mad cow disease" could prior to gene transfer. The presence of be eliminated by deleting the gene 10% to 20% of the altered casein in two decades, including ani- leading to the disease. milk produced by a transgenic cow mals that produce greater Milk improvements. Variations in could increase proteolysis (eg,pro- the composition and functionality as- tein breakdown) and thereby promote cheese yields and healthier sociated with milk proteins, such as the faster ripening of cheese. Results of milk for human consump- leading to more efficient cheese-making experiments with transgenic mice il- or new types of cheese, suggest that. lustrate the positive effects of adding tion, as well as a .wider changes in these properties should be genes such as casein (GutiCrrez-Adan range of milk products.

62 CALIFORNIA AGRICULTURE, VOLUME 54. NUMBER 4 ing animals that produce greater in surface water cheese yields and healthier milk for and groundwater, human consumption, as well as a damaging aquatic wider range of milk products. life and contami- For example, the increased expres- nating drinking sion of certain milk proteins could water. yield animals that produce milk specifi- Reducing phos- cally for manufacturing and industrial phate pollution of purposes, such as for cheese-making water is a major versus fluid-milk consumption. Alter- challenge for natively, our research program is de- swine, poultry and signed to improve the nutritional and finfish producers. antimicrobial properties of milk in- To the extent that tended for human consumption. Our enzymes can be laboratory at UC Davis has already added to increase shown that human lysozyme, when the efficiency of expressed as a transgene in mice, feed additives, the maintains antimicrobial activity, some amount of that ad- of which is enhanced when lysozyme ditive in the feed is secreted by the mammary gland ver- can be reduced. If sus simply adding lysozyme to milk a more effective (Maga et al. 1997). phytase (an en- Experiments are currently under- zyme that breaks way to add other naturally occurring down phytic acid, human milk proteins - also having a phosphate- antimicrobial properties - and genes containing ring to alter the fatty-acid composition of compound pro- milk in favor of a more heart-healthy duced by plants) mix. can be expressed Dairy cows carrying these types of in the animal‘s di- transgenes could become available by gestive tract, then 2025. Using transgenic cows could re- the amount of sult in the gradual separation of the phosphate in the At UC Davis, Gary Anderson and coi- genetic backgrounds of herds being diet can be re- leagues are conducting experiments to used for fluid milk production from duced, and this in turn would lower alter the fat composition and antimicrobial those used for producing milk for the amount of unused phosphate it ex- properties of milk produced by mice, and cheese manufacturing. For example, cretes. Such “environmentally eventually, dairy cows. the antimicrobial properties of friendly,” genetically modified ani- lysozyme-containing milk for drinking mals could become available to vari- and then the herds must undergo se- could interfere with the microbes used ous livestock industries within 10 to 15 lection to optimize performance for in cheese and yogurt production. years. the desired traits. This will be particu- Greater specialization among dairy larly important for transgenes affect- herds could result, with some herds Issues and concerns ing quantitative traits such as growth, earning premiums for producing spe- The potential application of cloning body composition and reproduction, cific types of milk for particular niche and genetic engineering technology to and for transgenes that modify inter- markets. livestock raises a number of important mediary metabolism. Environmental protection. Live- issues. Research on the integration of a stock production, particularly inten- Integration of a transgene into a transgene into a breeding population sive systems like dairy, swine, poultry breeding population. Transgenic ani- using a model system has begun only and aquaculture, needs to reduce the mals could become useful in produc- recently. The introgression of a amount of minerals excreted by ani- tion agriculture within 20 years. How- transgene into livestock will be expen- mals. Because the digestive processes ever, production of a useful transgenic sive, due to the cost of breeding. A sec- of livestock can be inefficient, com- line is only the first step toward intro- ond cost stems from the lack of selec- pounds such as phosphate are usually ducing the transgene into a production tion and thus genetic improvement added to feed at levels exceeding the population. during the period when the transgene animals’ dietary requirements. These ~ To begin with, the transgene must is being inserted and integrated into minerals accumulate at elevated levels be transferred to core breeding herds, the breeding population.

CALIFORNIA AGRICULTURE, JULY-AUGUST 2000 63 males, will depend on economic incen- tives. If the cost of stock or loss in selection progress is greater than the re- turn to the producer through increased efficiencies or income over a reasonable period, producers will not use these technologies. In cases where the transgene results in new products, such as antimicrobial milk or moth-resistant wool, the producer would probably need to obtain a premium price to convert the production flock or herd to the new genotype. As with antimicrobial milk, the introduction of some new genotypes may lead to segmenting the industry and creating special uses for different populations of animals so that new "breeds" are established. In the end, if scientists have done a good job in selecting traits to be manipulated, the acceptance of genetically modified animals by industry will come Genetic engineering may be able to reduce groundwater pollution by improving down to whether or not consumers enzymes in the digestive tracts of livestock animals, thereby reducing the amount of are prepared to buy the resulting phosphates they must consume and excrete. Lagoons are one of the practices currently products. employed by dairies to manage animal waste. Consumer acceptance. Debate continues in Europe, Japan and the Gama et al. (1992) suggested that of inbreeding among livestock. A priori United States over the use of geneti- the best strategy for introgressing a there is no reason to assume that ei- cally modified crops. In the United transgene into a core swine herd ther of these impacts will result to a States, a number of genetically modi- would involve three generations of greater extent than when conventional fied crops have been approved by the backcrossing before selecting a herd breeding techniques are used. U.S. Department of Agriculture for and evaluating their characteristics. If cloned animals, which by defi- commercial use. There is every reason Backcrossing involves crossing an off- nition exhibit virtually no genetic to assume that the introduction of ge- spring with one of two parental popu- variation, are properly used within netically modified livestock will en- lations. The economic benefits of the the context of a selective breeding gender similar public debate. Concerns transgene affecting a production trait program, then inbreeding should be range from decreasing genetic diversity or production efficiency must be suffi- minimized. The same is true for and the safety of genetically moditied ciently high to compensate for these transgenic animals, which are more foods to animal welfare issues. costs. inbred than the population at large, For genetically modified crops in Recent results of research with GH- whether produced by microinjection cultivation, plants have been modified transgenic mice show that the herita- or cloning. In either case, the reliance to resist herbicides or insect pests. The bility of various body-composition on a limited number of founder ani- traits that have been genetically engi- traits is altered and that the traits that mals could lead to increased inbreed- neered into plants so far are similar to result from transgene expression may ing, while the selection by industry the growth-enhancing transgenes in be dependent on the genetic back- of a limited number of production animals. Because they affect produc- ground of the strains or breed line genotypes, like breeds today, could tion traits rather than the quality of the (Siewerdt et al. 1999). It cannot be as- lead to reduced genetic diversity in final product, consumers may not per- sumed that the transgene will neces- the gene pool over a prolonged pe- ceive any direct benefits to them or sarily yield the same desired traits riod. Maintenance of genetic diver- may believe the benefits are not worth when placed in different genetic back- sity is desirable to allow future im- the perceived costs. grounds. provements through breeding for Genetic diversity and inbreeding. production and health traits. Future in focus: Another potential concern is whether industry acceptance. The accep- Adoption depends on cost the use of cloning or genetically engi- tance of genetically engineered ani- Biotechnology has contributed to neered animals will lead to reductions mals by industry, as with the use of the genetic improvement of farm ani- in genetic diversity or increased rates cloning to reproduce exceptional fe- mals for decades, through artificial in-

64 CALIFORNIA AGRICULTURE, VOLUME 54, NUMBER 4 semination and embryo transfers. production may already be available, References Transgenic technology and cloning while results from transgenic mice Gama LT, Smith C, Gibson JP. 1992. can, and indeed should, be success- demonstrate the potential to manipu- Transgene effects, introgression strategies fully used to increase the genetic merit late milk and improve its properties and testing schemes in pigs. Anim Prod of livestock. Transgenic sheep, goats, for manufacturing and human con- 541427-40. Gordon JW, Scangos GA, Plotkin DJ, et pigs and cattle can now be made rou- sumption (Murray et al. 1999). Genes al. 1980. Genetic transformation of mouse tinely, although the efficiency still is and promoters are being identified on embryos by microinjection of purified DNA. low and the costs high, particularly for a massive scale through various ge- Proceedings of the National Academy of Sci- ences USA 77:7380-4. cattle. nome mapping and functional Gutibrrez-AdAn A, Maga EA, Meade HM, Sheep, goats, pigs and cattle have genomics initiatives. et al. 1996. Alteration of physical characteris- been successfully cloned, but again the While commodities such as milk tics of milk from bovine kappa-casein efficiency is low. While the cost of pro- and fiber can be genetically modified, transgenic mice. J Dairy Sci 79:791-9. Jimenez-Flores R, Richardson T. 1988. duction is not a major concern when many economically important produc- Genetic engineering of the caseins to modify producing transgenic animals for bio- tion traits, such as growth, require ge- the behavior of milk during processing: A re- medical or pharmaceutical production netic modification of basic metabolic view. J Dairy Sci 71:2640-54. Maga EA, Murray JD. 1995. Mammary purposes, it poses a considerable bar- systems. Until recently, research on gland expression of transgenes and the po- rier to the introduction of these tech- the most appropriate strategies and tential for altering the properties of milk. Biol niques for production animals in agri- potential problems arising from the in- Technology 131452-7. culture, particularly given the low trogression of transgenes into produc- Maga EA, Anderson GB, Cullor JS, et al. 1997. Antimicrobial properties of human level of public funding for animal agri- tion populations with different genetic lysozyme transgenic mouse milk. J Food Pro- cultural research (see p. 72). backgrounds has largely been ignored. tection 61 52-6. The advent of cloning as a method We are optimistic about the future Murray JD, Maga EA. 1999. Changing for producing genetically engineered of transgenic animals in agriculture. the composition and properties of milk. In: Murray JD, Anderson GB, Oberbauer AM, animals may increase our ability to We predict that by midcentury most McGloughlin MM (eds.). Transgenic Animals produce transgenic livestock. Because agricultural animals will be genetically in Agriculture. Wallingham, UK: CAB Inter- the transgene is inserted during the engineered to be more efficient and national. 304 p. Murray JD, Anderson GB, Oberbauer AM, cell-culture phase, each offspring born healthier than current stock, produc- McGloughlin MM (eds.).1999. Transgenic will be transgenic, and each will have ing healthy products for human con- Animals in Agriculture. Wallingham, UK: CAB the same insertion site. If the efficiency sumption in an environmentally International. 304 p. of cloning is improved, then the effi- friendly system. Nottle MB, Nagashima H, Verma PJ, et al. 1999. Production and analysis of transgenic ciency of producing transgenic ani- Although the low efficiency of cur- pigs containing a metallothionein porcine mals will also be increased. The fact rent genetic engineering technology is growth hormone gene construct. In: Murray that transgenic animals are clones is a limiting factor, the need to carry out JD, Anderson GB, Oberbauer AM, relevant only to the extent that care selection to optimize the performance McGloughlin MM (eds.). TransgenicAnimals in Agriculture. Wallingham, UK: CAB Interna- must be taken to avoid inbreeding. of transgenic production animals may tional. 304 p. The ability to re-derive animals from be an even greater limiting factor in Pinkert CA, Murray JD. 1999. Transgenic cells in culture finally opens up the the development of commercial herds. farm animals. In: Murray JD, Anderson GB, Oberbauer AM, McGloughlin MM (eds.). possibility of doing experiments to The cost of producing suitable TransgenicAnimals in Agriculture. eliminate undesirable genes and traits transgenic animals for use in produc- Wallingham, UK: CAB International. 304 p. in livestock (called gene knockout or tion herds versus the potential eco- Purse1 VG, Wall RJ, Mitchell AD, et al. gene replacement). nomic benefits could limit the use of 1999. Expression of insulin-like growth factor- I in skeletal muscle of transgenic swine. In: The results of recent work with such animals. As we move into the Murray JD, Anderson GB, Oberbauer AM, growth-enhanced transgenic pigs in- 21st century, we must engage in two McGloughlin MM (eds.). Transgenic Animals dicate that it is possible to control dialogues: one with the agricultural in Agriculture. Wallingham, UK: CAB Intema- animal industry to determine the most tional. 304 p. systemic-acting transgenes so that de- Siewerdt F, Eisen EJ, Murray JD. 1999. sirable effects are obtained without the important areas to target for manipu- Direct and correlated responses to short-term health impairments seen in earlier ex- lation and another with the public so selection for 8-week body weight in lines of periments. The mammary gland and that consumers fully understand the transgenic (oMtla-oGH)mice. In: Murray JD, Anderson GB, Oberbauer AM, McGloughlin the milk protein systems are robust nature of the genetic changes being MM (eds.).Transgenic Animals in Agriculture. and can be altered and added to using introduced. Wallingham, UK: CAB International. 304 p. a variety of different proteins and will Wall RJ, Hawk HW, Nel N. 1992. Making still function normally. Furthermore, 1.0. Murray is Professor, Department of transgenic livestock: Genetic engineering on a large scale. J Cell Biochem 49:113-20. these systems can be altered to pro- Animal Science, College of Agricultural and Wilmut I, Schnieke AE, McWhir J, et al. duce predictable changes in the func- Environmental Sciences, and Department of 1997. Viable offspring derived from fetal and tional and antimicrobial nature of Population Health and Reproduction, School adult mammalian cells. Nature 385810-3. Yom HC, Richardson T. 1993. Genetic en- milk. of Veterinary Medicine, UC Davis. G.B. gineering of milk composition: modification of Current research suggests that ani- Anderson is Professor and Chair, Depart- milk components in lactating transgenic animals potentially useful for commercial ment of Animal Science, UC Davis. mals. Amer J Clin Nutr 58:2998-3068.

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