Volume 5, Issue 1

Can you tell if any ofthese animals are

transgenic?

Can you tell if any ofthese animals are

transgenic?

Developing aTransgenic Animal

Healthier Foods,Healthier Animals

Pharm Animals

Animal Models ofHuman Disease

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From Wolf to Poodle -Taming and Changing Animals

Developing aTransgenic Animal

Meanwhile, Back on the Pharm: AnimalsMaking Medicine

Animal Models of Human Disease

1415 Class Project

Predicting Traits

Volume 5, Issue No. 1

Your World/Our World describes the application ofbiotechnology to problems facing our world. Wehope that you find it an interesting way to learnabout science and engineering.

Development by:The Pennsylvania Biotechnology Association,The PBA Education Committee, andSnavely Associates, Ltd.Editing and Writing by:The Writing Company, Cathryn M. Delude andKenneth W. MirvisDesign by:Snavely Associates, Ltd.Educational Advisors:Barbara McHaleGraphic Consultant:Dustin LandisScience Advisor:Ramesh Kumar, Nextran, Princeton, NJSpecial Advisor:Raymond C. Dobert, U.S. Department of Agricul-ture, Beltsville, MD

Special Thanks:The PBA is grateful to the members of theEducation Committee for their contributions:Naomi Biswas, Esq. � Synnestuedt & Lechner

Keith Buckingham, Grant Calder, and MichaelCanfield � Friends' Central School

Stephen R. Collins � JRH Bioscience

Roberta Cook � The Franklin Institute

Jeff Davidson � Pennsylvania BiotechnologyAssociation

Alan Gardner � SmithKline BeechamPharmaceuticals

Cynthia Gawron-Burke

Kodzo Gbewonyo, Brittany Herman, Dustin Landis,and Althea Talento � Merck & Company

Marion Guthrie � Guthrie Associates

Barbara L. Handelin � Handelin Associates

Daniel Keller � Keller Broadcasting

Byron Long � Bristol-Meyers Squibb

Barbara McHale � Gwynedd-Mercy College

Lois Peck � PRIME, Philadelphia College ofPharmacy and Science

Lisa Speicher

Laurence A. Weinberger, Esq.

If you would like to make suggestions orcomments about Your World /Our World, drop us aline at:CompuServe: 73150,1623Internet: 73150.1623 @ compuserve.com

Healthier Foods, Healthier Animals

Our Long Relationship with Animals

Cover:You can't tell from looking at them if animals are transgenic�meaning they carry anadded gene. The two piglets on the left of the upper left photo are transgenic. They are partof a research project that hopes to find an inexpensive way to produce a valuable medicalprotein. They carry a gene that will make this protein in their milk when they grow up.

Photo Credits:Background and upper left: U.S. Department of Agriculture, Agricultural Research ServiceLower left: Penn State Photographic ServicesLower middle: Terry Wild Studios

Pennsylvania Biotechnology Association1524 W. College Avenue, Suite 206State College, Pennsylvania 16801

Copyright 1995, PBA. All rights reserved.

The Science of Breeding

Profile

Vernon G. Pursel, Animal Physiologist

3

Taming and Changing Animals

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People tamed the wolf more than 12,000years ago and have been developing newbreeds ever since.

neering. These changes will be passedto future generations through normalreproduction.

Transgenic technology allows us tomeet the traditional goals of breeding� giving plants or animals specifictraits � more quickly and precisely. Italso allows us to develop traits wecould not develop through traditionalbreeding. This issue of Your World/Our World concentrates on the devel-opment of transgenic animals andsome potential applications. The fieldof transgenic animals is very youngand, as you will see, still has manyhurdles to cross. n

Since the beginning of our time onearth, people have relied on plantsand animals for survival � and wehave bred those animals and plantswith traits we have found most help-ful. In prehistoric days, we tamed thewolf and created the dog, and wedomesticated a wild grain to createcorn. Throughout the ages, we haveselected plants and animals withvaluable traits and bred them. Hunt-ers bred dogs with specialized skillssuch as sniffing, retrieving, or chas-ing. Farmers cultivated plants toproduce more grain and cows to givemore milk. Breeding across similarspecies gave us the hardy mule (across between a donkey and a horse)and new fruits and vegetables such asthe tangelo (a cross between a grape-fruit and a tangerine).

Today, genetic engineering allows usto breed transgenic plants and ani-mals. The meaning of the word�transgenic� has changed over time.Originally it meant usinggenetic engineering totransfer the genes from onespecies to another species.For instance, we trans-ferred an insect-fightinggene from a bacterium to atomato to give the tomatopest resistance, and wehave given a cow a humangene that allows it to make a medica-tion in its milk. Today, we call anyplant or animal �transgenic� if itcarries an added gene, whether thegene is from a different species, thesame species, or is a synthetic genethat does not exist in nature. We callthese added genes transgenes.

All transgenic plants or animals haveone thing in common. Their geneticmaterial, or genome, has been perma-nently changed through genetic engi-

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As you read this issue,keep a log of your thoughts.� How does transgenic technol-

ogy continue the goals of tradi-tional agriculture?

� How does it change these goals?

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These technicians are analyzing DNA tests on a computer to help farmers know whichanimals carry genes for desirable and undesirable traits. This information helps themselect which animals to breed.

Science ofBreedingTheThe

Natural Selection andSelective BreedingEven before people appeared on earth,the genes of animals were continuallychanging, evolving over thousands ofyears to form new species. Becausethe natural environment promotedthese changes in species, we call thisprocess of change �natural selection.�When people began to use animals ascompanions, workers, and sources offood, we began to promote changesin many species through �artificialselection� or �selective breeding.� Wechose animals with valuable traits tobreed in order to develop the traits weliked, generation after generation.

Genetic Science UnveilsHidden Causes of TraitsIn the past, farmers decided whichanimals to breed based only on whatthey could observe, such as theamount of milk a cow made. Thethings we observe are �phenomena,�and so observable traits are calledphenotypes. Today, we recognizethat genes (interacting with theenvironment) are the basis for theseobservable traits. The specific geneticinformation that causes a trait is thegenotype, or gene structure. Scien-

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This farmer talks with an agriculturalconsultant about his herd.

Career Tip:FarmingFarmers raise animals, feed them, keep

them free of disease, and get their food productsto market. It has always been a year-round job.Today, farmers must do even more than just workhard. They must be high-tech jacks-of-many-trades, with knowledge in the areas of chemistry,biotechnology, and finance. Look for related agri-cultural careers throughout this magazine.

5

FROM ONE CELL TO WHOLE ANIMAL

1) In animals, the repro-ductive cells are thefemale’s egg and themale’s sperm. Repro-ductive cells have only onecopy of each chromo-some, unlike other cellswhich have a pair of eachchromosome. Thechromosomes are longstrands of DNA carryingdifferent genes.

2) Immediately after asperm fertilizes an egg, thefertilized egg contains twopronuclei (singular:pronucleus), one from thesperm and the other fromthe egg.

3) After a few hours,the pronuclei combineand form pairs ofchromosomes.

4) The fertilized eggdivides into two cells,each of which containsan identical copy ofthe genes from thefertilized egg.

5) Each new cell dividesinto two more cells, eachcarrying copies of theoriginal genes.

6) After a large number ofcell divisions, the embryodevelops through stages tobecome a fetus. As cellsdivide, they develop intomore specialized tissuesand organs. Somebecome reproductivecells, which are laterresponsible forreproducing theanimal.

tists are identifying many genes inthe DNA of different animals. As aresult, we can now examine whathappens at the genetic level whenanimals breed, including processeswe could not observe or predict be-fore. (You can explore this process inthe activity on page 14.) Today, farm-ers can test their animals� DNA to seewhether they carry the genes fordesirable or undesirable traits, thustaking the �guesswork� out of breed-ing. In fact, modern farmers are bigcustomers for companies that testDNA.

Custom-Made GenesGenetic engineering allows us to domore than just select animals tobreed based on their genes. We canalso change genes in very specificways by using recombinant DNAtechnology. �Recombinant� comesfrom the word �recombine,� which isbasically what we do to genes. Wecan �cut� a gene out of a strand ofDNA, �copy� (clone) it, and �paste�(insert) it into another strand ofDNA. In this way, we can constructcustom-made genes, called trans-genes, and insert them into ananimal�s reproductive cells (egg orsperm). This ability to insert genesinto reproductive cells is the key stepin developing transgenic animals. n

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Fertilized rat eggs, magnified 250 times.The egg in the upper right corner isbeginning to divide.

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Fertilized pigegg withtwo pronuclei

Microinjection pipette

Transgenes

4 months

1 year

Creation of Transgenic Animals

In a laboratory, a fertilized eggis microinjected with a transgene.

The fertilized egg with the transgeneis implanted into a mother pig.

Some of the offspring maycarry the transgene and can passit on to their young.

About 50% of their offspringwill be transgenic. Breedingtransgenic offspring can producea herd of transgenic animals.

The transgenic offspring is matedwith a non-transgenic pig.

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D e v e l o p i n g A Transgenic AnimalMicroinjection:Inserting a Transgeneinto a Reproductive CellTo develop a transgenic animal,scientists must insert a transgene intoa reproductive cell (sperm or egg).The most common technique fordoing this insertion is microinjection.

First, female animals receive a hor-mone that makes them release manyeggs. These eggs are then fertilizedand removed. A laboratory technicianholds the fertilized eggs in place witha pipette under a microscope whileinjecting several hundred copies of atransgene into a pronucleus.

Ideally, the transgene will insert itselfinto a chromosome and will become apermanent part of the genome. (How-ever, using current technology, only1% to 3% of the fertilized eggs usuallycarry the transgene.) The fertilizedeggs are then implanted in femaleanimals, where they will develop intoembryos.

If the transgene has become part ofthe genome, it will be present in everycell of the animal that develops, and itwill be passed to following genera-tions through regular sexual repro-duction. In theory, the transgenicoffspring will express the gene; that is,it will make the protein �encoded� bythe gene. In early experiments,though, the transgenes were not al-ways expressed.To understandwhy they werenot, we had tolearn moreabout thestructure of agene, how it isregulated, andthe right wayto design atransgene.

A laboratory technician holds a fertilized egg inplace by a pipette while copies of a transgeneare injected into a pronucleus.

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Microinjection, magnified 250 times.

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Creation of Transgenic Animals

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Super Regulatory ElementCoding Section

Transgene

Promoter

Stop

Compare therates at whichpigs and cowscan give birth

to offspring. About how many litters can apig have in one year? About how long wouldit take one cow to have as many offspringas a pig can have in one litter? Can youthink of some reasons why many research-ers use pigs instead of cows?

PIGS COWS

Gestation period(from conception to birth) 4 months 9 months

Average number of offspring 12 1

Time before mother can 1 month 2.5-4 months breed again

Age at which offspring canbreed 6 months 1 year

What�s in a Gene?The function of most genes is toproduce or express a protein. Someproteins become part of a cell�sstructure and others help regulate acell�s processes. In making proteins,different parts of the gene performdifferent functions (see diagram). Acoding section contains the instruc-tions for making a particular protein.The regulatory sections control whenand where the protein is made. Oneof the regulatory sections, the pro-moter, allows the gene to be turnedon in a cell. Another regulatory part,called the super regulatory element,controls how many copies of theprotein the gene makes (its �level ofexpression�). Still another regulatorypart acts as the stop signal.

Gene ExpressionAn animal has many types of cellsthat form tissues such as skin, brain,and mammary glands, and each celltype makes a different combinationof proteins. Every cell in an animalcarries all the genes in its genome,but only a fraction of those genes are

A transgene contains several elements, all of which are part of the same DNA molecule. A gene's coding section is sandwiched betweenregulatory sections, which are shown in red.

• The “super regulatory element” controls the number of copies of a protein that the gene will make.

• The “promoter” is the start signal for the gene.

• The “coding” section specifies the type of protein the gene makes.

• The “stop” signal indicates the end of the gene.

expressed in any one cell. Many geneshave specific expression, meaningthey are expressed only in certaintypes of cells or tissues. For example,the genes for milk proteins are ex-pressed only in the cells of mammaryglands.

Why are some genes expressed in onecell but not another? The answer liesin the nature of the proteins alreadycontained in the nucleus of the cell.These nuclear proteins, called tran-scription factors, are required for theexpression of genes. If the righttranscription factors are presentin the nucleus, the gene will beexpressed. If these proteins are miss-ing, the gene remains silent. Forexample, the cells of the mammaryglands have the transcription factorsthat �turn on� the genes that producemilk proteins.

Transgenes in TroubleIn its natural form, every gene has a�home address,� a specific locationon a certain chromosome. At itshome address, the gene can be easilyexpressed. However, when a transgene

is microinjected into an egg, it cango to another address or even toanother chromosome. Such mis-directed genes may or may not turnon, or they may make too littleprotein. That is why some transgenicanimals do not express the proteinthe transgene is supposed to pro-duce, or they express it at too low alevel to be helpful.

Designer Transgenes tothe RescueWe can help ensure that transgeneswill work at any address in thegenome by combining the righttissue-specific promoters and superregulatory elements with the protein-coding sections of the gene. The�modular� structure of a transgenethus opens up many possibilities forexpressing different proteins indifferent tissues. Depending on whatwe want the gene to do, we can mixand match the sections of DNA fromdifferent sources to create a designertransgene. You can read about someof these possibilities in the followingarticles. n

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has now fathered many calves.About half of them are transgenic,and of those, the females are pro-ducing human lactoferrin in theirmilk!

One day, we may be able to add thislactoferrin to infant formula. Sci-

entists still need to testthis milk for effective-ness, and it will need topass many food safetyrequirements. If success-ful, medical researchersexpect to find additionaluses for lactoferrin�santi-bacterial activity.They even foresee usingit to strengthen the im-mune systems of peoplewith cancer, AIDS, andother health problems.

Herman, the first bull with the gene for humanlactoferrin, lives with his calves in the Netherlands.

Human Milk from a Cow!When you were born, you did nothave a lot of immunity � the abilityto fight different diseases. If yourmother breastfed you, you got a largedose of immunity from the proteinsand antibodies in her milk. If youdrank formula instead,you did not have thebenefit of those proteinsand antibodies. Formula,usually made from cow�smilk or soybeans, lackssome of these ingredi-ents that are so good fornewborn babies. One ofthese proteins, calledhuman lactoferrin, helpsprevent bacterial infec-tions that cause digestiveproblems that harm orkill millions of newbornsaround the world. Thereis no efficient way tomake human lactoferrinartificially. However,there may soon be a new�natural� source, thanksto our ability to construct a designertransgene for tissue-specific expres-sion of a protein.

Since human lactoferrin is producedin the mammary glands, how do youthink it could be produced in ani-mals? If you answered, �In the mam-mary glands of other milk-producingmammals, like cows,� then you thinklike a genetic engineer!

Scientists first isolated the gene forhuman lactoferrin. Then they cre-ated a transgene by combining theprotein-coding section of thelactoferrin gene with a regulatorysequence that is recognized by the

cells of a cow�s mammary glands.Using microinjection, they put thistransgene into fertilized cows� eggsand implanted the eggs in fostermother cows. The first calf bornwith the human lactoferrin genewas a bull named Herman. Herman

H e a l t h i e r Fo o d ,H e a l t h i e r

Animals

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These scientists are developing a line oftransgenic chickens that will be free ofdisease by giving them disease-resistantor disease-fighting genes.

Low-Fat Meat, Disease-Free AnimalsFuture transgenic developmentsmay make both people and animalshealthier. Some researchers aredeveloping animals that can resistcommon diseases. Others are work-ing to develop animals that convertmore of their food to muscle and lessto fat. If successful, these animalsmight give us leaner beef, leanerpork, and low-cholesterol eggs�foods that could help reduce manyhealth problems in people.

SuperFishSince fish are a source of plentifuland low-fat protein, many peopleare interested in increasing fishproduction as a way of feeding theworld�s growing population. Oneway to increase fish production isto make fish grow faster and larger.In some experiments, scientistshave given various fish the growthhormone gene from the fast-grow-ing freshwater trout. Thesetransgenic fish grow faster andlarger than their natural cousins.

Other research focuses on increas-ing the conditions under whichcertain fish can live. Scientistshave given salmon the Arcticflounder's �antifreeze� gene thatmakes it possible to survive in coldtemperatures. This antifreezegene could allow the salmon to beraised in colder waters than itsnormal habitat.

These transgenic fish are part of arelatively new field of �aquaculture,�where commercial fish are raised infenced-in fish farms (and will not bereleased into the wild). Can youguess where the word �aquaculture�comes from? n

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Better Cheese

To make cheese, wemix milk with a proteincalled “rennin” which

makes the milk curdle. Tradi-tionally, rennin comes fromthe inside of a calf’s stomach,where it helps the calf digestmilk. Biotechnology has al-ready changed the art ofcheese-making by develop-ing a new source for rennin.Now, transgenics may furtherrefine cheese-making by ge-netically engineering cows sothey make milk that curdlesmore easily and consistently.This specialized milk couldlower the price of cheese andgive it a better quality.

• What benefits would comefrom disease-resistant strainsof farm animals?

• For the foreseeable future,transgenic fish will be raised inconfined fish farms. What mighthappen if they mixed with the“wild” fish in the ocean?

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Animals Making Medicine

A transgenic sheep namedTracy and her lambsproduce a protein in theirmilk called Alpha-1-antitrypsin (AAT). Thisprotein may help treathereditary emphysema,a disease of the lungsthat makes breathing sodifficult that many peoplemust use an oxygen tankto survive.

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Across the North Sea from Hermanthe bull, Tracy grazes with herlambs in the Scottish highlands.On the other side of the AtlanticOcean, a herd of goats romp in afield in Massachusetts. Like

Herman�s calves, these animals areraised not for their traditional agri-cultural products (meat, milk, orwool), but for a specialized proteinthe females make in their milk.The goal of these experiments is to

one day use these proteins to treatdiseases in people. Because suchtransgenic animals produce medi-cines or �pharmaceuticals,� scien-tists have dubbed them �pharm�animals.

Are dogs “man’s best friend” – or might itbe pigs? Pigs are biologically very similarto humans, and so they are the source ofmany life-saving medical products.

A New Source forHuman Blood ProteinsIf you have ever had a terrible cut,you know how much you can bleed.To keep people alive when they havelost a lot of blood, doctors give themtransfusions. Hospitals always needblood for transfusions in operationsand emergencies.

Hospitals use huge quantities ofblood � 10 million pints a year in theU.S. Where does all this blood comefrom? You may have seen �blooddonation drives� around town, wherepeople donate some of their blood tobe stored. In spite of these donors, itis difficult to keep enough bloodstored for medical needs.

If the milk from transgenic cows, goats,and sheep contains medical proteins inthe concentrations listed in the chart,

how many of each animal would you needto make the needed quanitity of thesemedicines?

Milk production Quantity Number ofAnimal Protein per animal* Concentration* needed animals

Cows lactoferrin 20 liters/day 1g/l 100kg/day

Goats AT III 1.5 liters/day 100mg/l 1kg/day

Sheep AAT 1 liter/day 10mg/l 100g/day*NOTES: These are hypothetical quantities only. 1000mg=1g,1000g=1kg; g=gram, mg=milligram, kg=kilogram

These goats produce aprotein in their milk calledantithrombin-III (AT-III). AT-III is normally present inhuman blood and preventsclotting in the veins. Peoplewith an inherited deficiency(lack) of this protein areprone to blood clots, whichare dangerous when theybreak free and lodge in thelungs or brain.

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Now, some scientists are developingan alternative supply � a blood sub-stitute made from hemoglobin, thecomplex protein in red blood cellsthat transports oxygen. One possibleway is to use transgenic pigs thatproduce human hemoglobin in theirown blood as blood donors. Thehemoglobin could be purified fromtheir blood and used to create ablood substitute to give to humanpatients. Because pigs are so easy tobreed, they could provide an unlim-ited supply of inexpensive hemoglo-bin. This supply could help solve theproblem of blood shortages.

Transgenic OrganTransplantsYou may have heard newsstories about childrenwaiting for a liver orheart transplant. Whatmakes their condition sosad is that they must waitfor another, healthyperson to die, usuallyfrom an accident orinjury. Every year in theUnited States, more than16,000 lives are saved bytransplants, yet 3,000 people die(and countless more remain sick)while waiting for an organ.

How can we increase the supplyof healthy organs? One way is toencourage more people to donatetheir organs. Some scientists areexploring another possibility �transplanting organs from trans-genic pigs.

Pig organs are about the same size ashuman organs. We already use thevalves from pigs� hearts for humanheart valve transplants and pig skinfor skin grafts for burn victims. Butorgan transplants are much morecomplicated than heart valves orskin grafts.

Normally, we could not use pigs�organs because our bodies wouldcompletely reject them. Non-humanorgans have foreign proteins that tellour bodies they are dangerous in-truders. Our antibodies and immune

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because human organs have a pro-tein that identifies them as human.(Human organs are rejected by aslower immune reaction which canoften be overcome by drugs.) Scien-tists identified the gene for that hu-man-friendly protein and developedtransgenic pigs that express it in theirorgans. Theoretically, these organswill not be immediately rejected bythe human immune system.

Overcoming this immediate rejec-tion is just the first step towardscross-species organ transplants,called �xenotransplants.� (Theprefix �xeno� means foreign.) Manyother major technical problems mustbe resolved before pig organs can beused in transplants. n

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In its natural state, hemoglobin (the complex protein that carries oxygen in the blood) iscontained within a cell. In blood substitutes, hemoglobin exists in solution rather than in acell. Without an additional chemical - called a “cross-linker” - that hemoglobin complexcould fall apart and would be toxic to the kidneys. Cross-linkers help hold the hemoglobintogether in blood substitutes and prevent toxicity. In this model, the chemical cross-linkeris the green and white threads in the center of the image.

cells immediately attack a foreignorgan and destroy it. This immediateextreme reaction does not occurwhen human organs are transplanted

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Making a Blood Substitute from Transgenic Pigs

CrudeHuman

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Research several diseases forwhich vaccines or treatmentsare available (such as polio,diabetes, cancer, cystic fibro-sis). Do any of these proce-dures rely on animal models?Was there an alternative tousing animals for this re-search?

Heart disease is a leading cause ofdeath in the U.S. In fact, you prob-ably know someone who is beingtreated for it. One common causeof heart disease is atherosclerosis,a thickening and hardening of thearteries (major blood vessels). Inthis condition, fat builds up insidethe arteries, clogs them, reducesthe flow of blood, and increasesblood pressure. The person youknow with this condition probablytakes a medicine to help reducethese life-threatening problems.How do doctors know if the medi-cine works? If it is safe? What doseto use?

Before we start usingmedicine for people,we see how itworks in animalswith a similar

disease. That way, we can study ifthe medicine is safe and how well ittreats the disease. Since the begin-ning of the 1900s, scientists haveused traditional breeding tech-niques to develop laboratory ani-mals with the traits of certainhuman diseases. We call these spe-cialized animals �models� of hu-man disease. We use them to learnmore about diseases, to find treat-ments or cures, and to test newmedicines.

Transgenic technology allows usto create more specialized animalmodels, such as transgenic micethat have the disease atherosclero-

sis. These mice express two humanproteins that cause an accumula-tion of cholesterol in their bloodstream. The mice eventuallydevelop atherosclerosis and, likepeople, accumulate fat in theirarteries. Using these mice, scien-tists can test medicines that lowercholesterol levels before givingthem to people. These transgenicmice may lead to a better treat-ment for one of the biggest healthproblems in this country. n

The transgenic mouse on the right is a model for atherosclerosis, a human disease that causeshardening and thickening of the arteries. The mouse on the left is a normal, healthy mouse. Theviews below show a magnified cross section of their arteries. A stain was used to show the fattydeposits, which appear red in the photo. The transgenic mouse has much more fat in the arterythan the normal mouse. Scientists are using these transgenic mice to find new drugs to treat thiscommon disease in people.

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Our LongRelationship with

percherons

Traditional breeding techniques led to thedevelopment of these large, strongPercheron horses that can pull heavyloads. The horses shown here participatein pulling competitions.

Animals

We have many relationships withanimals. They are our pets and ourbeasts of burden. We raise them forracing and for �showing�, and totest cosmetics, medicines and tox-ins. They have always provided uswith meat, eggs, milk, wool, leatherand fur, and more recently, medi-cines such as insulin. Now somepeople want them to produce newkinds of medicines as well as trans-plant organs. We have always bredanimals for our benefit. Transgenictechnology can fine-tune thosebenefits. Which of these uses can wejustify � and why? All? None? Some?

Attitudes Towards AnimalsSome people who study moral issues� questions of �right and wrong� �have defined three basic attitudestowards animals. Do your beliefs fitinto any of these categories?

1) Animal Exploitation: Humanneeds are always higher than ani-mals. Therefore, people can useanimals any way we like.

2) Humane Use of Animals: We haveto balance human needs and animalneeds. While we can use animals forour benefit, we cannot abuse them.We can raise them for food andother products as long as we killthem painlessly, and we can doexperiments on them if we do notcause them unnecessary suffering.

3) Animal Rights: Animals have thesame moral status as people, and itis not right for us to use them forour own benefit. We should no

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Animals

Has animal biotechnologyredefined our relationship withanimals? How is it differentfrom what came before?How is it a continuation ofthe same goals?

What standards should wefollow for treating animalswell? Should we havedifferent standards foranimals raised for agricultureand those used in medicalexperiments?

more experiment on them than weshould on people who cannot takecare of themselves.

Animal Well-BeingCongress and other governmentagencies have passed strict regula-tions about the treatment of ani-mals based on the principle thathumans are responsible for thewell-being of animals in our care.(This principle is an outgrowth ofposition #2 above.) For example,animals raised for medical experi-ments must not suffer unnecessar-ily and should have a naturallifestyle and freedom of movement.When researchers use animals, theymust use the fewest number pos-sible and the least painful proce-dures available.

Some animal rights advocates, how-ever, want to prevent many uses ofanimals, including all medical ex-periments and transgenic research.Today, more and more researchersare doing their work using �non-animal models.�

Patenting LifeSome people are not opposed totransgenic research, but they objectto the patenting of transgenicanimals. A patent is a kind of tem-porary �ownership� of a technologi-cal invention, and it prevents othersfrom copying the invention withoutpermission and payment of a roy-alty (fee). Some people think it isimmoral to patent transgenic ani-mals because living creatures arenot human creations or machines.On the other hand, developingtransgenic animals is a very longand expensive process, and compa-nies depend on future royalties topay for this development. Withoutpatents, many important advancesin medicine and nutrition that couldhelp millions of people worldwidemight slow or stop. n

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variation (lower case letter �a�).Notice that the chromosome pairsare similar in that they have thesame genes, but they have differentvariants of each gene. The combina-tion of these variations determineswhich traits will show.Recessive traits appear only when tworecessive genes are present; otherwisethe dominant traits appear. Figure 2shows the traits determined by thegenes on the chromosome. Of course,this example is overly simplified; inreality, most traits are determined bythe interaction of many genes and theenvironment.In this activity, you will analyze thegenotypes and phenotypes of theseanimals and their potential offspring.For example, if a male has thesegenes in Chromosome 1: Aa, Bb,and tt, he has dominant phenotypesfor A and B, and a recessive phenotypefor t. He will have a solid coat, browneyes, and a curly tail.

Directions1) Copy the chromosome strips

in Figure 1 onto two separatesheets of paper. Copy thefemale's chromosomes ontowhite paper and the male'schromosomes onto coloredpaper.

2) Label four cups as follows:female 1, female 2, male 1, andmale 2.

3) Cut the chromosomes into verticalstrips and separate chromosome 1from chromosome 2. Place them intheir respective cups. (Note that youare separating the duplicated chro-mosomes from one another by cut-ting through the centromere, andyou are also separating the relatedchromosome pairs from one an-other.)

4) Put the male cups together and thefemale cups together.

5) Randomly select one chromosomefrom each of the two male cups andplace them together to create the�sperm.� Now create the �egg� byfollowing the same procedure withthe female chromosomes. (Note thatthe egg and sperm each contain only

one of each of the chromosomes. Theegg and sperm have half the totalnumber of chromosomes as cells inthe rest of the body.)

6) Put the chromosome strips that youselected together to represent thefertilized egg, which has one of eachchromosome from both parents. Pairthe chromosomes by whether they area �1� or a �2�.

7) Analyze the genes from the two chro-mosomes and record each phenotypeand genotype. Your teacher will showyou how to organize a chart.

8) Put all the strips back into their respec-tive cups and repeat this procedureagain (starting with #5). Repeat itseven more times, recording the re-sults for all eight trials on the chart.

Discussion1) Do some offspring have blue eyes,

when neither parent did?2) Does the phenotype of the parents

predict all the possible outcomes forthe offspring? In other words, if bothparents have brown eyes, will all theiroffspring have brown eyes?

3) We would expect these ratios for thesephenotypes:

� 3/8 of the offspring would be B_P_(brown eyes and long horns).

� 1/8 of the offspring would be bbP_(blue eyes and long horns).

� 3/8 of the offspring would be B_pp(brown eyes and short horns).

� 1/8 of the offspring would be bbpp(blue eyes and short horns)How did the outcomes of your eighttrials compare to the predicted out-comes?Note: Blanks (_) accompany dominantgenes, since the dominant traits showno matter what the other gene is.

4) If you combine the results of all thetrials in your entire class, do the num-bers get closer to the predicted out-comes? Can you explain why or whynot? n

Figure 2: Dominant and RecessiveVariationsDominant RecessiveA solid coat a spotted coatB brown eye s blue eyesT straight tail t curly tailC high milk c low milkE normal nails e reduced nailsN healthy blood n blood diseaseP long horn p short horn

Figure 1: Chromosome Pairs

BackgroundThis exercise demonstrates the randomseparation and reassortment of chromo-somes during sexual reproduction. Thisreshuffling of chromosomes creates varia-tions in genetic material (genotypes) andobservable traits (phenotypes) that we seeamong individuals in a species.Figure 1 shows two pairs of chromosomesfor both female and male during thecreation of the egg and sperm. Each chro-mosome in each pair has duplicated; thereare now two identical copies of each pair.The duplicated chromosomes are still heldtogether by a structure called the �cen-tromere� (the large dot).The letters on the chromosomes representgenes. (The numbers are only for identifi-cation during your activity.) Each genehas two variations: a dominant variation(upper case letter �A�) and a recessive

PREDICTING TRAITS

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Vernon G. PurselA n i m a l P h y s i o l o g i s t

V ern Pursel grew up on adairy farm in westernNevada, and he always knew

he would devote his life to workingwith animals. As a young boy, he wasactive in the 4-H Club and FutureFarmers of America, raising his ownpigs and calves. He went to theUniversity of Nevada to get a B.S. inAnimal Husbandry, expecting to gointo farming. His plans changedwhen, in his senior year, he becameinspired by a laboratory researchcourse in animal physiology. Hewent on to get a Ph.D. in Dairy Hus-bandry from the University of Minne-sota and soon accepted a position asResearch Physiologist with the U.S.Department of Agriculture�s Agricul-tural Research Service in Beltsville,Maryland. Almost thirty years later,Dr. Pursel has received many awardsfor his pioneering work in animalresearch.

Early in his career, Dr. Pursel helpeddevelop a technique for preservingfrozen semen for artificial insemina-tion in pigs (in which the female eggis fertilized without mating). Thistechnique allows farmers worldwideto improve the quality of their herds.

This work led Dr. Pursel to geneticengineering and techniques formicroinjecting transgenes into fertil-ized eggs. Microinjection was origi-nally only possible with mice andrabbits, since their eggs are clearenough for the laboratory technicianto see the pronuclei. The eggs of pigs

and cows, however, are cloudybecause they have a lot of fat.

�Trying to find a pronucleus is liketrying to see a golf ball in a glass ofmilk,� Dr. Pursel explained.

He and his team developed a methodusing a high-speed centrifuge, spin-ning the egg so the fat collects onone side, revealing the pronuclei thatremain in the center. This methodopened the door to transgenicresearch in pigs, cows, and otherlarge mammals.

Once opened, the door led Dr. Purseldown several paths. One direction ledto transgenic pigs that will produceantibodies against bacteria that causepneumonia and digestive diseases.Another direction involved trans-genic pigs that will produce a humanprotein to treat a rare geneticdisease at a much lower cost thancurrent treatments. Still anotherinvolved transgenic pigs that willhave more lean meat and less fat.They have a transgene for a growthhormone that allows them to convertmore of their feed to muscle ratherthan fat. Such pigs would not onlyproduce healthier meat for humanconsumption, they would alsorequire less feed and produceless waste.

All of these projects are still indevelopment, and they all requireextensive teamwork and many kindsof skills. �If one person drops theball, everything goes down thedrain,� Dr. Pursel commented. �The

There are almost endless pos-sibilities for transgenic animalapplications. Can you think ofan application that you wouldlike to develop? How wouldyou go about it? How would itbenefit humanity? How wouldyou fund your research? Howwould you sell your product?

USDA, Agricultural Research Service

people that take care of our pigs arejust as important to the success ofour research as those of us that planthe experiments.�

Dr. Pursel has come a long way fromhis rural roots in Nevada, and hiscareer has changed somewhat fromhis original goal. He still is devotedto working with animals, and he ishappy that his work might producesomething good for people worldwide.

Profile:Profile:

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Dear Students:

The generosity and support ofthese sponsors have made theproduction of Your World/OurWorld possible. Please join usin thanking them:

Read More About It!Read More About It!Your World/Our World:Vol. 2, No. 1 (DNA profile)Vol. 2, No. 2 (plant biotechnology;

DNA transcription/translation)Vol. 3, No. 1 (producing medicines

through fermentation; rennin forcheese)

Vol. 3, No. 2 (vaccines and theimmune system)

Vol. 4, No. 1 (development of drugsand patents)

Science World, Feb. 24, 1995.“Debate: Organ Transplant,” p. 17

National Agricultural BiotechnologyCouncil Reports, 1992. AnimalBiotechnology: Opportunities andChallenges.

Online References for AgBioResources:Global Agricultural BiotechnologyAssociation:http://www.lights.com/gaba/onlin.html

Biotechnology Information Center:http://www.inform.umd.edu/EdRes/Topic/AgrEnv/Biotech

Access Excellence:http://www.gene.com:80/ae

Other Contacts:Animal Welfare Information CenterNational Agricultural Library10301 Baltimore Blvd.Beltsville, MD 20805Tel: 301-504-6212

Biotechnology Information CenterNational Agricultural Library10301 Baltimore Blvd.Beltsville, MD 20805-2351Tel: 301-504-5340

National Agricultural BiotechnologyCouncil (NABC)158 Biotechnology Bldg.Cornell UniversityIthaca, NY 14853Tel: 607-254-4859

Correction to Vol. 4, #2, Gene Therapy,page 3 graphic: The middle circle in theillustration should have shown thechromosomes as separate strands, notas an X-shaped figure.

Preview of the Next Issue:The Human Genome Project.Don't miss it!

Supporting OrganizationsUtah State University BiotechnologyCenter

SponsorsBiotechnology Industry Organization

Connaught Laboratories, Inc.

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Merck Institute for Science Education

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We are pleased to provide you with this issue ofYour World/Our World. We hope you find it aninteresting way to learn more about bio-technology. Biotechnology can be important toyou for two reasons:1. During your lifetime there will be tremendousdiscoveries in this field, and you'll want tounderstand what those discoveries mean foryou, your friends, and your family.

2. You can help make those discoveries if youdecide to continue to study science and math.

Either way, we hope you join us in discoveringthe promise of biotechnology for our world. Weare pleased to acknowledge the support of thecompanies listed. Their support makes thismagazine possible.

Sincerely,

Jeff DavidsonExecutive DirectorPennsylvania Biotechnology Association