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CALIFORNIA AGRICULTURE, JULY-AUGUST 2000 57

Genetic engineering and cloning may improvemilk, livestock productionJames D. Murray ❏ Gary B. Anderson

In the past, procedures such asartificial insemination and embryotransfer have been used in the ge-netic manipulation of livestock.Advances in gene and quantitative-trait mapping will enhance thesetraditional animal-breeding ap-proaches to improve farm ani-mals. By genetically engineeringlivestock, scientists hope to pro-duce animals with altered traitssuch as disease resistance, woolgrowth, body growth and milkcomposition. Laboratories world-wide have produced transgenicpigs, sheep, goats and cattle, butcurrently the efficiency of produc-ing the animals remains low andthe procedure is expensive.

Traditionally, genetic improve-ment of livestock has been

achieved by applying the principlesof quantitative genetics and animalbreeding. Milk production in dairycattle, for example, has increased100 pounds of milk per cow peryear due to genetic selection, aug-mented by artificial insemination.Advances in gene and quantitative-trait mapping in the last decade willensure that traditional animal-breeding approaches, coupled withnewer techniques for marker-assisted selection, will be effectivein providing continued genetic im-provement of livestock. The adventof modern biotechnology also pro-vides new avenues for genetic im-provement in production animals.

Within the next few decades, how-ever, genetically engineered dairycows could become available.Cloning may also be used to du-plicate animals with traits that aredifficult to capture through tradi-tional breeding practices. By2025, cloning and breeding of eliteanimals could be carried out bycompanies comparable to thosethat now comprise the artificial in-semination industry, which se-lects and breeds top dairy stock.The acceptance of geneticallyengineered animals by industrywill depend on its economic ben-efits and whether consumers areprepared to buy the resultingproducts.

Transgenic sheep, goats, pigs and cattle are now routinely made, although efficiencyis low and costs are high. Conventionally bred sheep are herded near Cholame.

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58 CALIFORNIA AGRICULTURE, VOLUME 54, NUMBER 4

Backcrossing: crossing an offspring toone or the other of two parentalstrains or breeds.

DNA: deoxyribonucleic acid, the mol-ecule containing the genetic code.

Embryonic stem (ES) cells: undifferenti-ated cells derived from embryos andcapable of surviving prolonged cul-ture while still contributing to devel-opment of viable offspring. Embry-onic stem cells can integrate foreignDNA. Laboratory techniques can iso-late ES cells that have integrated thetransgene at a specific site in thegenome.

Expression: production of a protein orother molecule from a gene coded inthe DNA.

Gene construct: man-made DNA mol-ecule used to produce a transgenicanimal.

Gene knockout: disruption of the func-tion of a specific gene. Currentlygene knockouts require ES celltechnology.

Gene replacement: substitution of onegene for another. Like knockouts, tar-geting a particular gene now requiresES cell technology.

Genome: the complete set of genetic in-formation for an individual.

Heritability: measure of the extent towhich an observed trait is controlledby genetics as compared to the envi-ronment in which the animal lives.

Inbreeding: mating of close relatives,leading to a reduction in genetic di-

versity in the offspring and increas-ing the likelihood of expression ofdeleterious genes.

Introgression: movement of a gene fromone population to another.

In vitro: in the laboratory, outside theorganism.

Lysozyme: naturally occurring proteinwith antimicrobial properties.

Marker-assisted selection: use of DNA-based markers to aid in selectivebreeding for or against a specifictrait.

Micelle: assembly of milk proteins into aparticle.

Overexpression: increased expression ofa gene above the normally observedlevel.

Phenotype: physical characteristics of anindividual.

Promoter: part of a gene that controlswhen and where in an animal a geneis expressed.

Pronucleus: structure containing geneticmaterials from the egg or sperm in arecently fertilized egg.

Quantitative traits: genetic traits con-trolled by many genes that influenceproduction such as growth rate, fer-tility and milk production.

Site-directed mutagenesis: an intro-duced change in a gene at a specific,targeted site in the gene.

Transgene: genetic material introducedby means other than natural breeding(an animal carrying a transgene is re-ferred to as being transgenic).

In the broadest sense, biotechnol-ogy includes procedures commonlyused in animal production, such as ar-tificial insemination and embryo trans-fer — both of which have successfullyincreased the rate of genetic improve-ment in species. During the past 10 to15 years, however, the term biotech-nology has come to be associated morewith molecular-based technologies,such as gene cloning and geneticengineering.

The initial development of tech-niques for cloning and manipulatinggene sequences in the 1970s was fol-lowed 10 years later by techniques for

producing genetically engineered ortransgenic animals, resulting in a para-digm shift in modern biological re-search (Gordon et al. 1980). Initial suc-cesses with transgenic mice weresubsequently extended to agriculturalspecies. Laboratories worldwide haveproduced transgenic pigs, sheep, goatsand cattle (Pinkert and Murray 1999).However, the efficiency of producingtransgenic ruminants and pigs re-mains low, the costs are high and thetime required to produce and charac-terize transgenic livestock is long(Wall et al. 1992). For example, deter-mination that the introduced gene is

passed to a transgenic animal’s prog-eny requires that the originaltransgenic animal reach sexual matu-rity and then complete at least onegestation period. This could take sev-eral years in some species.

Microinjection of DNA into the pro-nuclei of recently fertilized ova is themost common technique used to pro-duce genetically engineered livestock,but on average fewer than 2% of mi-croinjected embryos yield transgenicindividuals. Furthermore, pronuclearmicroinjection has allowed only therandom integration of a transgene intothe animal genome.

Since 1980, scientists have madecontinual advances in the efficiency ofproducing embryos from farm animalsin the laboratory, called in vitro matu-ration and fertilization. These tech-niques, combined with improved con-ditions for embryo culture andcryopreservation and increased expe-rience and sophistication in the pro-duction and manipulation of embryos,culminated in the cloning of an adultsheep, “Dolly,” by Scottish scientists in1997 (Wilmut et al. 1997).

Advances in animal cloning proce-dures, beginning with transgenic do-nor cells, have also resulted in the pro-duction of transgenic sheep, goats andcattle. Although today’s overall effi-ciency appears to be comparable tothat of pronuclear microinjection, clon-ing to produce transgenic livestockwill allow the insertion of DNA se-quences — as embryonic stem cells doin mice — creating the opportunity toalter or remove a specific gene (fig. 1).

With continued scientific improve-ments, the production of transgeniclivestock through cloning could even-tually be more efficient than pro-nuclear microinjection. Modern bio-technology can be used to improve thegenetic merit of livestock by tworoutes: transferring novel genetic ma-terial via genetic engineering or accel-erating the dissemination of desirabletraits via the cloning of selected indi-vidual animals.

Cloning and genetic improvement

The successful cloning of an adultsheep (Wilmut et al. 1997) captured

Glossary


Fig. 1. Transgenic farm animals are produced by direct microinjection of DNA intoyoung embryos and by cloning from transgenic somatic cells. Microinjection proce-dures use recently fertilized eggs, which for some species can be obtained from in vitrofertilization procedures, before the first cell division. If the foreign DNA becomes inte-grated into the embryonic genome at the one-cell stage, as the embryo develops all ofits cells will contain the transgene. The offspring that is born after transfer of the em-bryo to the reproductive tract of a recipient female will be transgenic. Alternatively, so-matic cells can be collected from an animal, cultured in the laboratory, and exposed toforeign DNA. Some cells will become transgenic, and these cells can be selected for useas nuclear donors in nuclear-transfer procedures. The resulting nuclear-transfer embryowill be transgenic, as will the offspring born after embryo transfer and term developmentin the reproductive tract of a recipient female.

the imagination of both the scientificcommunity and the rest of the world.Dolly — the sheep cloned from a cul-tured mammary gland cell of a 6-year-old ewe long since dead — made thecover of most major news and scien-tific magazines and became the subjectof global commentary and debate. Lostin the debate was a primary reason be-hind the investigators’ experiments:the identification of cell types thatcould be genetically manipulated inthe laboratory and subsequently usedto generate a transgenic animal.

Developments in cloning havetaken two forms since Dolly’s birth:demonstrations of the practical uses ofcloning to produce transgenic animals,and the expansion of the species andtypes of cells that can be used asnuclear donors in successful cloning.Transgenic fetal fibroblasts — isolatedand engineered from connective tissuecells — have been used to clonetransgenic lambs, calves and goat kids.

Successful cloning from adult cellshas been expanded to include variouscell types in cattle and laboratorymice. The potential to clone adult ani-mals creates entirely new dimensionsfor animal agriculture. A desirable andunique specimen can be precisely re-produced, capturing traits that are dif-ficult to develop through traditionalbreeding practices. For example, adairy cow that produces milk with un-usually high milk protein content(which is important for makingcheese), or with an unusually low per-centage of saturated fat (which has hu-man health benefits), could be cloned.Selective breeding from an individualanimal is not always successful, butselective breeding from a nucleus coreherd of cloned animals is more likelyto succeed.

An example of the power of cloningis the preservation of the last surviv-ing cow of the Australia’s Enderby Is-land cattle breed. Cloning of this femaleand use of available cryopreserved se-men to breed the surviving clones couldprovide a second chance to resurrect abreed that otherwise would havedisappeared.

We can only speculate about whatimpact cloning technology will have

on genetic improvement, but potentialimpacts could be considerable for in-tensively managed systems such as thedairy industry. Early in the 21st cen-tury, cloning could be used to dupli-cate the top-producing dairy cows. Ar-tificial insemination eliminates theneed to clone elite bulls, but at presenteach elite cow can produce only a lim-ited number of offspring, even with

the use of embryo transfer technology.The ability to clone genetically elite

females, while possibly increasing thelevel of inbreeding, also increases theintensity of genetic selection. By 2025,cloning and breeding of these clonedanimals could be carried out by compa-nies comparable to the current artificial-insemination industry, which is re-sponsible for selection and breeding

Sperm

Unfertilized egg

A micropipetteinjects DNA solutioninto the fertilized egg

Culturedsomatic cells(The blue cells

have been madetransgenic)

Nuclear-transferembryo

Transgenic2-cell

sheep embryo

Transgeniclamb


of the top dairy stock. The swine in-dustry could undertake a similar strat-egy for the expansion of the clonedlines of top breeding sows.

Livestock with improved traits

During the 15 years since the firsttransgenic farm animals were pro-duced, the rationale for genetic engi-neering of livestock for agriculturalpurposes has been to produce animalswith altered traits such as disease re-sistance, wool growth, body growth ormilk composition. In most instances,the objective has been either to altertraits for improved production effi-ciency or to alter the properties of theanimal product, such as wool or milk,and increase the range of manufactur-ing options.

Gene constructs — designed to ex-press directly or indirectly variousgrowth factors and alter body compo-sition — constitute the largest class oftransgenes transferred into livestockspecies. The majority of thesetransgenes expressed growth hormone(GH), although other constructs basedon GH release and insulin-like growthfactor-I (IGF-I) also have been used. Ingeneral, pigs and sheep expressingthese constructs were leaner and morefeed-efficient. But as a result of high,

unregulated levels of circulating GH,they also suffered a number of compli-cations, such as joint problems, indi-cating the need for tight control of hor-mone secretion.

Recently, two research groups re-ported preliminary data on the develop-ment of GH and IGF-I transgenic pigswith enhanced growth-performancetraits (Nottle et al. 1999; Pursel et al.1999). In both experiments, desirableeffects on growth and body composi-tion traits were achieved without ap-parent abnormalities, suggesting thatsomeday useful animals could becomeavailable to swine breeders. Poten-tially useful GH-transgenic fish alsohave been produced, but biologicalcontainment of the transgene is ofgreat concern in species with existingwild fish populations.

Milk protein genes have beencloned from a variety of mammals.The promoter elements from certainmilk-protein genes from one or morespecies have been used to facilitate ex-pression of transgenes in the mam-mary glands of mice, sheep, goats,cattle, rabbits and pigs (Murray andMaga 1999). These transgenes are de-velopmentally correct, but their levelsof expression can vary. Research ontargeting transgene expression to the

mammary gland of farm animals ei-ther has focused on studying the pro-moter function or on the productionand recovery of biologically impor-tant, active proteins for use as pharma-ceuticals (Maga and Murray 1995).

Several private companies haveproduced transgenic cows, sheep,goats and pigs, targeting transgenicexpression to the mammary glandwith the aim of isolating high-valuepharmaceutical proteins from milk.But the use of transgenesis for agricul-tural purposes, such as to alter theproperties and composition of milkand change the functional propertiesof the milk protein system, is also pos-sible by adding a new gene or alteringan existing gene.

We have produced transgenic micethat express human lysozyme or amodified bovine casein (a protein usedin cheese-making and for some indus-trial purposes) in the milk. As a result,we have measured alterations in thephysical and functional properties ofthe mouse’s milk protein system, in-cluding decreased micelle size and in-creased gel strength. The productionof human lysozyme in milk oftransgenic mice also increased the an-timicrobial properties of the milk,which in cows could reduce infections

This transgenic goat has a transgene that codes for a humanprotein under the control of a promoter region that targets ex-pression specifically to the mammary gland. The human proteinis secreted in the goat’s milk but nowhere else in the animal.

A recently fertilized bovine embryo (zygote) is microinjected tointroduce a DNA solution into its genetic material. Microinjectionof zygotes is currently the most common method to producetransgenic animals.

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In the 21st century, “precisionfarming” will improve the effi-

ciency of livestock production aswell as agricultural crops, making itpossible for producers to identifyand manage large animals individu-ally even while in a herd.

Improvements in information re-sources and technology include ad-vances in computer hardware suchas increased internal data storageand portability (e.g., CD-ROM) andprocessing capacity, new softwarefor decision support systems, andthe World Wide Web with its in-credible collection of data.

Online sensors of animal physi-ological attributes will continue tobe integrated with these tools forbetter-automated livestock manage-ment systems. For example, na-tional species-specific databaseshave been developed to supportdecision-making by farmers andranchers and those who work withthem in educational, consultation orservice capacities (Oltjen 1998;Kunkle and Troxel 2000). Distrib-uted via CD-ROM and the Web,these comprehensive databases forbeef, sheep, pigs and other animalsprovide electronic collections ofpeer-reviewed and expert-selected

educational materials, lists, soft-ware tools and other decision aids.

Further, the Web will continue toincrease its usefulness, supplyingmarketing information, facilitatingdirect-marketing, and allowing two-way communication between live-stock consultants and producers.These tools are already bringinguseful information to the farms,homes and offices of livestock pro-ducers operating in even the mostremote rural communities.

In the future, individual largeanimals will be linked to specificdatabases, allowing for improvedanimal selection and herd manage-ment. Such systems are already a le-gal requirement in the EuropeanEconomic Community and arewidely used by dairy producers inmany other countries. The NationalCattlemen’s Beef Association (1999)has called for a voluntary programin the United States to utilize track-ing and database technology to en-hance food safety, provide informa-tion for better management andimprove product quality and indus-try profitability.

When such systems are in place,the interdependence of all segmentsof the livestock industry becomes

apparent. Several private companieshave introduced databases which al-low all participants in livestock pro-duction systems, from providers ofanimal genetics to sellers of consumer-ready products, to capitalize on infor-mation to solve complex industry-wide problems as well as those ofindividual producers and firms.

Historically, change has occurredslowly on small farms and in the de-veloping world. But with access to theWeb and advanced information re-sources, there is no reason why thelack of knowledge should limit tech-nological progress in livestockproduction.

J.W. Oltjen is Extension Animal Manage-ment Systems Specialist, Department ofAnimal Science, UC Davis.

ReferencesKunkle W, Troxel T. 2000. The Beef

Infobase. The ADDS Center, Verona, WI.www.adds.org.

Oltjen JW. 1998. The National Sheep Da-tabase. The ADDS Center, Verona, WI.www.adds.org.

National Cattlemen’s Beef Association.1999. Live Cattle Marketing, Grading, CattleIdentification Systems Policy M4.7.Englewood, CO.

Advanced information systems toimprove livestock management

James W. Oltjen

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In the future, individualanimals will be linked todatabases for improvedanimal selection and herdmanagement. UC Davisanimal science profes-sors Juan Medrano andEd DePeters identify acow by scanning a micro-chip embedded in its leg.


in the mammary gland and perhapseliminate undesirable pathogens inthe gut of humans who consume themilk.

Alternative scenarios

Two scenarios demonstrate how ge-netic engineering can be applied to im-prove livestock. The first involves al-tering milk to improve functionalityand human health. In the second sce-nario, genetic engineering is used toreduce environmental pollution stem-ming from animal agriculture andaquaculture. Other useful applicationsare possible; perhaps diseases such asscrapie and “mad cow disease” couldbe eliminated by deleting the geneleading to the disease.

Milk improvements. Variations inthe composition and functionality as-sociated with milk proteins, such asleading to more efficient cheese-makingor new types of cheese, suggest thatchanges in these properties should be

possible. Richardson and colleaguesproposed specific alterations in theproperties of milk that might beachieved by overexpressing, deletingor adding back a mutated form ofmost major milk protein genes(Jimenez-Flores and Richardson 1988;Yom and Richardson 1993). For ex-ample, adding extra copies of thecasein gene to overexpress caseincould increase the thermal stability ofmilk, reducing protein breakdownduring manufacturing.

A more complex proposal would beto alter a casein gene at a specific site(called site-directed mutagenesis)prior to gene transfer. The presence of10% to 20% of the altered casein inmilk produced by a transgenic cowcould increase proteolysis (e.g., pro-tein breakdown) and thereby promotethe faster ripening of cheese. Results ofexperiments with transgenic mice il-lustrate the positive effects of addinggenes such as casein (Gutiérrez-Adán

We expect geneticallyengineered dairy cows tobecome available withintwo decades, including ani-mals that produce greatercheese yields and healthiermilk for human consump-tion, as well as a widerrange of milk products.

et al. 1996) or human lysozyme (Magaet al. 1997) to the milk protein system.

Ongoing research, supported inpart by the industry’s California DairyResearch Foundation, is exploring po-tential uses of transgenic technology inthe dairy industry. We expect geneti-cally engineered dairy cows to becomeavailable within two decades, includ-

Within 20 years, transgenic and cloned animals could become useful in production agriculture. For these technologies to be comm er-cialized, issues such as the integration of transgenes into breeding populations, genetic diversity and inbreeding, and industr y andconsumer acceptance must be addressed.

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ing animals that produce greatercheese yields and healthier milk forhuman consumption, as well as awider range of milk products.

For example, the increased expres-sion of certain milk proteins couldyield animals that produce milk specifi-cally for manufacturing and industrialpurposes, such as for cheese-makingversus fluid-milk consumption. Alter-natively, our research program is de-signed to improve the nutritional andantimicrobial properties of milk in-tended for human consumption. Ourlaboratory at UC Davis has alreadyshown that human lysozyme, whenexpressed as a transgene in mice,maintains antimicrobial activity, someof which is enhanced when lysozymeis secreted by the mammary gland ver-sus simply adding lysozyme to milk(Maga et al. 1997).

Experiments are currently under-way to add other naturally occurringhuman milk proteins — also havingantimicrobial properties — and genesto alter the fatty-acid composition ofmilk in favor of a more heart-healthymix.

Dairy cows carrying these types oftransgenes could become available by2025. Using transgenic cows could re-sult in the gradual separation of thegenetic backgrounds of herds beingused for fluid milk production fromthose used for producing milk forcheese manufacturing. For example,the antimicrobial properties oflysozyme-containing milk for drinkingcould interfere with the microbes usedin cheese and yogurt production.Greater specialization among dairyherds could result, with some herdsearning premiums for producing spe-cific types of milk for particular nichemarkets.

Environmental protection. Live-stock production, particularly inten-sive systems like dairy, swine, poultryand aquaculture, needs to reduce theamount of minerals excreted by ani-mals. Because the digestive processesof livestock can be inefficient, com-pounds such as phosphate are usuallyadded to feed at levels exceeding theanimals’ dietary requirements. Theseminerals accumulate at elevated levels

in surface waterand groundwater,damaging aquaticlife and contami-nating drinkingwater.

Reducing phos-phate pollution ofwater is a majorchallenge forswine, poultry andfinfish producers.To the extent thatenzymes can beadded to increasethe efficiency offeed additives, theamount of that ad-ditive in the feedcan be reduced. Ifa more effectivephytase (an en-zyme that breaksdown phytic acid,a phosphate-containing ringcompound pro-duced by plants)can be expressedin the animal’s di-gestive tract, thenthe amount ofphosphate in thediet can be re-duced, and this in turn would lowerthe amount of unused phosphate it ex-cretes. Such “environmentallyfriendly,” genetically modified ani-mals could become available to vari-ous livestock industries within 10 to 15years.

Issues and concerns

The potential application of cloningand genetic engineering technology tolivestock raises a number of importantissues.

Integration of a transgene into abreeding population. Transgenic ani-mals could become useful in produc-tion agriculture within 20 years. How-ever, production of a useful transgenicline is only the first step toward intro-ducing the transgene into a productionpopulation.

To begin with, the transgene mustbe transferred to core breeding herds,

and then the herds must undergo se-lection to optimize performance forthe desired traits. This will be particu-larly important for transgenes affect-ing quantitative traits such as growth,body composition and reproduction,and for transgenes that modify inter-mediary metabolism.

Research on the integration of atransgene into a breeding populationusing a model system has begun onlyrecently. The introgression of atransgene into livestock will be expen-sive, due to the cost of breeding. A sec-ond cost stems from the lack of selec-tion and thus genetic improvementduring the period when the transgeneis being inserted and integrated intothe breeding population.

At UC Davis, Gary Anderson and col-leagues are conducting experiments toalter the fat composition and antimicrobialproperties of milk produced by mice, andeventually, dairy cows.

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Gama et al. (1992) suggested thatthe best strategy for introgressing atransgene into a core swine herdwould involve three generations ofbackcrossing before selecting a herdand evaluating their characteristics.Backcrossing involves crossing an off-spring with one of two parental popu-lations. The economic benefits of thetransgene affecting a production traitor production efficiency must be suffi-ciently high to compensate for thesecosts.

Recent results of research with GH-transgenic mice show that the herita-bility of various body-compositiontraits is altered and that the traits thatresult from transgene expression maybe dependent on the genetic back-ground of the strains or breed line(Siewerdt et al. 1999). It cannot be as-sumed that the transgene will neces-sarily yield the same desired traitswhen placed in different genetic back-grounds.

Genetic diversity and inbreeding.Another potential concern is whetherthe use of cloning or genetically engi-neered animals will lead to reductionsin genetic diversity or increased rates

of inbreeding among livestock. A priorithere is no reason to assume that ei-ther of these impacts will result to agreater extent than when conventionalbreeding techniques are used.

If cloned animals, which by defi-nition exhibit virtually no geneticvariation, are properly used withinthe context of a selective breedingprogram, then inbreeding should beminimized. The same is true fortransgenic animals, which are moreinbred than the population at large,whether produced by microinjectionor cloning. In either case, the relianceon a limited number of founder ani-mals could lead to increased inbreed-ing, while the selection by industryof a limited number of productiongenotypes, like breeds today, couldlead to reduced genetic diversity inthe gene pool over a prolonged pe-riod. Maintenance of genetic diver-sity is desirable to allow future im-provements through breeding forproduction and health traits.

Industry acceptance. The accep-tance of genetically engineered ani-mals by industry, as with the use ofcloning to reproduce exceptional fe-

males, will depend on economic incen-tives. If the cost of stock or loss in se-lection progress is greater than the re-turn to the producer through increasedefficiencies or income over a reasonableperiod, producers will not use thesetechnologies.

In cases where the transgene resultsin new products, such as antimicrobialmilk or moth-resistant wool, the pro-ducer would probably need to obtain apremium price to convert the produc-tion flock or herd to the new genotype.As with antimicrobial milk, the intro-duction of some new genotypes maylead to segmenting the industry andcreating special uses for differentpopulations of animals so that new“breeds” are established. In the end,if scientists have done a good job inselecting traits to be manipulated,the acceptance of genetically modi-fied animals by industry will comedown to whether or not consumersare prepared to buy the resultingproducts.

Consumer acceptance. Debatecontinues in Europe, Japan and theUnited States over the use of geneti-cally modified crops. In the UnitedStates, a number of genetically modi-fied crops have been approved by theU.S. Department of Agriculture forcommercial use. There is every reasonto assume that the introduction of ge-netically modified livestock will en-gender similar public debate. Concernsrange from decreasing genetic diversityand the safety of genetically modifiedfoods to animal welfare issues.

For genetically modified crops incultivation, plants have been modifiedto resist herbicides or insect pests. Thetraits that have been genetically engi-neered into plants so far are similar tothe growth-enhancing transgenes inanimals. Because they affect produc-tion traits rather than the quality of thefinal product, consumers may not per-ceive any direct benefits to them ormay believe the benefits are not worththe perceived costs.

Future in focus:Adoption depends on cost

Biotechnology has contributed tothe genetic improvement of farm ani-mals for decades, through artificial in-

Genetic engineering may be able to reduce groundwater pollution by improvingenzymes in the digestive tracts of livestock animals, thereby reducing the amount ofphosphates they must consume and excrete. Lagoons are one of the practices currentlyemployed by dairies to manage animal waste.

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semination and embryo transfers.Transgenic technology and cloningcan, and indeed should, be success-fully used to increase the genetic meritof livestock. Transgenic sheep, goats,pigs and cattle can now be made rou-tinely, although the efficiency still islow and the costs high, particularly forcattle.

Sheep, goats, pigs and cattle havebeen successfully cloned, but again theefficiency is low. While the cost of pro-duction is not a major concern whenproducing transgenic animals for bio-medical or pharmaceutical productionpurposes, it poses a considerable bar-rier to the introduction of these tech-niques for production animals in agri-culture, particularly given the lowlevel of public funding for animal agri-cultural research (see p. 72).

The advent of cloning as a methodfor producing genetically engineeredanimals may increase our ability toproduce transgenic livestock. Becausethe transgene is inserted during thecell-culture phase, each offspring bornwill be transgenic, and each will havethe same insertion site. If the efficiencyof cloning is improved, then the effi-ciency of producing transgenic ani-mals will also be increased. The factthat transgenic animals are clones isrelevant only to the extent that caremust be taken to avoid inbreeding.The ability to re-derive animals fromcells in culture finally opens up thepossibility of doing experiments toeliminate undesirable genes and traitsin livestock (called gene knockout orgene replacement).

The results of recent work withgrowth-enhanced transgenic pigs in-dicate that it is possible to controlsystemic-acting transgenes so that de-sirable effects are obtained without thehealth impairments seen in earlier ex-periments. The mammary gland andthe milk protein systems are robustand can be altered and added to usinga variety of different proteins and willstill function normally. Furthermore,these systems can be altered to pro-duce predictable changes in the func-tional and antimicrobial nature ofmilk.

Current research suggests that ani-mals potentially useful for commercial

production may already be available,while results from transgenic micedemonstrate the potential to manipu-late milk and improve its propertiesfor manufacturing and human con-sumption (Murray et al. 1999). Genesand promoters are being identified ona massive scale through various ge-nome mapping and functionalgenomics initiatives.

While commodities such as milkand fiber can be genetically modified,many economically important produc-tion traits, such as growth, require ge-netic modification of basic metabolicsystems. Until recently, research onthe most appropriate strategies andpotential problems arising from the in-trogression of transgenes into produc-tion populations with different geneticbackgrounds has largely been ignored.

We are optimistic about the futureof transgenic animals in agriculture.We predict that by midcentury mostagricultural animals will be geneticallyengineered to be more efficient andhealthier than current stock, produc-ing healthy products for human con-sumption in an environmentallyfriendly system.

Although the low efficiency of cur-rent genetic engineering technology isa limiting factor, the need to carry outselection to optimize the performanceof transgenic production animals maybe an even greater limiting factor inthe development of commercial herds.

The cost of producing suitabletransgenic animals for use in produc-tion herds versus the potential eco-nomic benefits could limit the use ofsuch animals. As we move into the21st century, we must engage in twodialogues: one with the agriculturalanimal industry to determine the mostimportant areas to target for manipu-lation and another with the public sothat consumers fully understand thenature of the genetic changes beingintroduced.

J.D. Murray is Professor, Department ofAnimal Science, College of Agricultural andEnvironmental Sciences, and Department ofPopulation Health and Reproduction, Schoolof Veterinary Medicine, UC Davis. G.B.Anderson is Professor and Chair, Depart-ment of Animal Science, UC Davis.

ReferencesGama LT, Smith C, Gibson JP. 1992.

Transgene effects, introgression strategiesand testing schemes in pigs. Anim Prod54:427-40.

Gordon JW, Scangos GA, Plotkin DJ, etal. 1980. Genetic transformation of mouseembryos by microinjection of purified DNA.Proceedings of the National Academy of Sci-ences USA 77:7380-4.

Gutiérrez-Adán A, Maga EA, Meade HM,et al. 1996. Alteration of physical characteris-tics of milk from bovine kappa-caseintransgenic mice. J Dairy Sci 79:791-9.

Jimenez-Flores R, Richardson T. 1988.Genetic engineering of the caseins to modifythe behavior of milk during processing: A re-view. J Dairy Sci 71:2640-54.

Maga EA, Murray JD. 1995. Mammarygland expression of transgenes and the po-tential for altering the properties of milk. Bio/Technology 13:1452-7.

Maga EA, Anderson GB, Cullor JS, et al.1997. Antimicrobial properties of humanlysozyme transgenic mouse milk. J Food Pro-tection 61:52-6.

Murray JD, Maga EA. 1999. Changingthe composition and properties of milk. In:Murray JD, Anderson GB, Oberbauer AM,McGloughlin MM (eds.). Transgenic Animalsin Agriculture. Wallingham, UK: CAB Inter-national. 304 p.

Murray JD, Anderson GB, Oberbauer AM,McGloughlin MM (eds.). 1999. TransgenicAnimals in Agriculture. Wallingham, UK: CABInternational. 304 p.

Nottle MB, Nagashima H, Verma PJ, et al.1999. Production and analysis of transgenicpigs containing a metallothionein porcinegrowth hormone gene construct. In: MurrayJD, Anderson GB, Oberbauer AM,McGloughlin MM (eds.). Transgenic Animalsin Agriculture. Wallingham, UK: CAB Interna-tional. 304 p.

Pinkert CA, Murray JD. 1999. Transgenicfarm animals. In: Murray JD, Anderson GB,Oberbauer AM, McGloughlin MM (eds.).Transgenic Animals in Agriculture.Wallingham, UK: CAB International. 304 p.

Pursel VG, Wall RJ, Mitchell AD, et al.1999. Expression of insulin-like growth factor-I in skeletal muscle of transgenic swine. In:Murray JD, Anderson GB, Oberbauer AM,McGloughlin MM (eds.). Transgenic Animalsin Agriculture. Wallingham, UK: CAB Interna-tional. 304 p.

Siewerdt F, Eisen EJ, Murray JD. 1999.Direct and correlated responses to short-termselection for 8-week body weight in lines oftransgenic (oMt1a-oGH) mice. In: Murray JD,Anderson GB, Oberbauer AM, McGloughlinMM (eds.). Transgenic Animals in Agriculture.Wallingham, UK: CAB International. 304 p.

Wall RJ, Hawk HW, Nel N. 1992. Makingtransgenic livestock: Genetic engineering ona large scale. J Cell Biochem 49:113-20.

Wilmut I, Schnieke AE, McWhir J, et al.1997. Viable offspring derived from fetal andadult mammalian cells. Nature 385:810-3.

Yom HC, Richardson T. 1993. Genetic en-gineering of milk composition: modification ofmilk components in lactating transgenic ani-mals. Amer J Clin Nutr 58:299S-306S.

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