GeneWatch Vol. 24 No. 2

GENEWATCHTHe mAGAZiNe oF THe CouNCil For reSpoNSible GeNeTiCS | ADVANCiNG THe publiC iNTereST iN bioTeCHNoloGy SiNCe 1983

PLUS: > National Geographic draws the ire of “the Last Incas”> Making music with your genome

> Exclusive interview: Mara Hvistendahl, Unnatural Selection

ISSN 0740›9737

“When does the use of biotechnology on animal bodies step over an ethicalline, or are their bodies open platforms for our biomechanical tinkering?”

- Paul Root Wolpe, page 4

Volume 24 Number 2 | April-mAy 2011

Whatever the researchers’ inten-tions, the projects that make the newsare often those which can most easilybe framed in an attention-grabbingway. The New Scientist dubs bioengi-neered animals “creatures with bonusfeatures,” and various websites andblogs have posted their lists of the “topten coolest” or “most bizarre geneti-cally modified animals.” In somebioengineered animals, pets in partic-ular, “coolness” is actually their primaryutility. GloFish (the name is self-explanatory) are marketed specificallyas pets, were granted approval for salein the U.S., and have already spawnedimitators—although their originalintended use was as a warning systemfor pollution levels in water.

It’s easy to get distracted by thebizarre bioengineered animals, but themajority of the most important onesdon’t glow under a UV light. “Knock-out mice,” engineered not to express acertain gene, are a lab standby andcould lead to “knockout monkeys.”Genetically modified salmon look justlike regular salmon, only larger, butthey pose very real risks to natural fish-eries and ocean ecosystems. Pigsmodified to be human organ donors arecertainly bizarre in concept, but on theoutside they still look like pigs.

Bioengineered animals are a strangelot, to be sure; but within that lot, as faras the impact a modified animal mayhave on the human and natural world,the book can rarely be judged by itscover.

Some opponents of various biotech-nologies—particularly geneticallymodified foods—have a tendency, evenwhen they could be citing scientific andeconomic studies that back their posi-tion, to fall back on the “yuck factor.”Illustrations of snarling anthropomor-phic cornstalks tend to grab one’sattention faster than carefully writtenarguments in a magazine. It may work,but vague queasiness and discomfortwith the unfamiliar are hardly therecipe for an educated opinion.

In discussions about bioengineeredanimals, the yuck factor is alive andwell. (Pigs that glow in the dark? Gross!)So too, however, is its counterpart, oneless common in discourse on GMcrops: the “cool factor.” As Paul RootWolpe points out (on page 4), it’s eas-ier to latch onto an individual case, anda number of individual animals havegained fame—or infamy—for their bio-engineering, with nicknames to boot.Our cast of characters includes:

Dolly: The first cloned sheep.The Beltsville pigs: Seventeen pigsdeveloped to express extra growth hor-mones, but suffered an array ofailments as a result and became an iconfor animal welfare activists.The Vacanti Mouse: Lab mouse withwhat looked like a human ear (actu-ally shaped cow cartilage) on its back.ANDi: Lab monkey genetically alteredwith a jellyfish gene, to make it glow.Enviropig: Developed to have reducedphosphorous levels in its manure.Popeye pigs: Purportedly healthierpigs as a result of an introduced spinachgene which lowered levels of saturatedfat.

2 GeNeWatch april-May 2011

Editor’s NoteBy SaMuElW. anDErSOn

GeneWatch welcomes article submissions, comments and letters to theeditor. Please email [email protected] if you would like to sub-mit a letter or with any other comments or queries, including proposalsfor article submissions.

Write (for) GeneWatch

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GEnEWatch is published by the Council for responsibleGenetics (CrG), a national, nonprofit, tax-exempt organ-ization. Founded in 1983, CrG’s mission is to foster publicdebate on the social, ethical, and environmental implica-tions of new genetic technologies. The views expressedherein do not necessarily represent the views of the staff orthe CrG board of Directors.

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april-May 2011 VoluMe 24 NuMber 2

unless otherwise noted, all material in this publication is protected by copyright bythe Council for responsible Genetics. All rights reserved. GeneWatch 24,2

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magdalina Gugucheva, Fellow

VoluMe 24 NuMber 2

Ethical Limits to BioengineeringAnimals

Humans have been using animals for our ownpurposes for a long time. Where do we draw

the line?PAUL ROOT WOLPE

Food and Drug AmalgamationThe FDA is readying to approve genetically

engineered salmon ... as a “drug”ERIC HOFFMAN

Food UnchainedResearchers are having a difficult time geneti-

cally engineering livestock to produce foodbetter than their non-engineered counterparts

SAMUEL W. ANDERSON

Goat PharmingAn interview with William Ravis, chief veteri-

narian at GTC BiotherapeuticsCRG STAFF

Back on “The Farm”The story behind an iconic painting and its

vision of the future, a decade laterROB DESALLE

Topic update: Federal Circuit Hears Appealin Myriad Gene Patent Case

SARS in the CityHow is it decided that an urban center is thesafest place to house a deadly, highly conta-

gious pathogen?LYNN C. KLOTZ

Gene Patenting in CanadaFrom the OncoMouse to cancer gene testing

and beyondJAMES J. RUSTHOVEN

Unnatural SelectionMore and more parents are gaining the abilityto choose the sex of their child ... now what?

INTERVIEW WITH MARA HVISTENDAHL

Sacred GroundsA community of “The Last Incas” bristles at

National Geographic’s attempt to collect their DNASAMUEL W. ANDERSON

Musical Genes The Genetic Music Project encourages musi-

cians to convert DNA code into musicINTERVIEW WITH GREG LUKIANOFF

Topic update: Massachusetts LegislatureHolds Hearing on Genetic Bill of Rights

Endnotes

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The history of humanity’s use of ani-mals for its own purposes is not a par-ticularly benevolent one. We haveused animal flesh for our meals and furfor warmth, bones for weapons andskin for parchment, blubber for oil andhorns for medicine. We have harnessedtheir bodies for labor and domesticat-ed them as companions. We have killedthem for sport, worked them to death,and used them for experiments with-out anesthesia.Today, we believe we are better. We

have laws against animal cruelty andstrong public sanctions for mistreat-ment of animals. At the same time,though, we have transformed individu-alized exploitation of animals intoindustrial animal processing. Eachyear, billions of chickens and millionsof turkeys have their beaks partially cutoff so that they can be crowded intowarehouse-sized barns without canni-balizing each other. Cattle are fedunnatural diets and sometimes castrat-ed without anesthesia, while geese areforce-fed to fatten them up for pâté. Of course, one could go on. No need

here to review the litany of our currentcruelties or to lament our lack of con-cern for the suffering of the animals weconsume; there is a vast literature onthose things and their ethical implica-tions (from Peter Singer’s AnimalLiberation [1975] to Jonathan SafranFoer’s Eating Animals [2009]). Yet,despite our general inattention to thequality of life of our livestock and poul-try, we still maintain that, as a society,we care about the treatment of ani-mals. We are outraged when a famousquarterback is caught with fightingdogs, we give money to save endan-gered species, we individually wash oil-

soaked birds in the gulf. We are deeply conflicted about our

treatment of animals as a society; sowhen we see the use of animal bodiesas platforms for genetic experiments, itis little wonder that we are confusedabout how to react.Our conflicted attitude toward ani-

mals expresses itself in many ways. Ioften present the idea of using trans-genic pigs to provide heart valves andwhole heart transplants to my under-graduate students as provocatively aspossible, by saying: “Imagine! You cancreate a drove of transgenic pigs whosehearts are not as immunoreactive tohumans, or, perhaps, even engineer apig to grow a heart using some genes

from the intended recipient. Then,when the heart is needed, you canchoose the best pig, slaughter it—maybe right in the hospital—and trans-plant the heart directly into the humanbeing!”The reaction is immediate and pas-

sionate, and predictable. Studentsobject that keeping pigs at the ready tobe slaughtered for hearts is wrong.“Why?” I ask. The best response I usu-ally get from students (or at least, thosewho have taken Intro to Philosophy) isthat it is using the animal entirely as ameans, and that is wrong. My nextquestion, of course, is whether they eatmeat.Why is it that students who had

bacon for breakfast react so strongly tothe idea of slaughtering a pig for itsheart? After all, no one is going to diewithout bacon, and we are sacrificingthe transgenic animal to save a person’slife.The answer lies in our tendency to

personalize morality. We are far morelikely to feel a responsibility to one per-son who is suffering than to groupswho are suffering. Charities raisingmoney for poverty in developingnations know it is far more effective totell one person’s story than to cite sta-tistics. It is also manifested in whatAlbert Jonsen referred to as the “rule ofrescue.”1 If you ask people whetherinsurance companies have a right not

to reimburse experimental, unproventreatments, a majority say yes.However, if you then give them a par-ticular case of a particular person—awoman with treatment-resistant breastcancer, for example—the same peoplethink it unconscionable that the insur-ance company will not pay for any andall experimental treatments, eventhose with only a remote chance ofhelping her. Personalize the case andour general principles often go out thewindow.Students feel sorry for that particular

chicken, or pig, but not so much forchickens and pigs in general. Thethought of slaughtering “pigs” forbacon seems not to offend some viscer-


Why is it that students who had bacon forbreakfast react so strongly to the idea of

slaughtering a pig for its heart?

Ethical Limits to Bioengineering Animals

Humans have been using animals for our own purposes for a long time. Where do we draw the line?

BY PAUL ROOT WOLPE

al sense of fairness, while slaughteringthat particular pig to put its heart inthat particular person seems to createan ethical calculus that we do not putinto play with masses of animals. Onedeath a tragedy, a million deaths a sta-tistic.The same reaction seems to be oper-

ative in our response to laboratory ani-mals. The same mice we can glue-trapor snap-trap in our basements must beeuthanized consistent with the recom-mendations of the AmericanVeterinary Medical Association Panelon Euthanasia when killed in a lab.Vermin in the home turn to protectedsubjects in the lab. The reactions to biotechnologically

engineered animals, then, becomecomplicated. Is there anythingreally wrong with using green flu-orescent protein to create a glow-ing rabbit, fish, or monkey?Should we protest the construc-tion of an ear-shaped polymerscaffolding on the back of amouse? Do we cross a line whenwe create flocks of transgenic ani-mals as bioreactors, or to be‘pharmed’ for drug molecules? Isit ethically questionable to wireelectrodes into animal brains to con-trol behavior, or to keep disembodiedanimal brains alive in nutrient media?With all the suffering that we bring toanimals caught up in agribusiness, is itnot better to create an animal that iswell taken care of, even if it has beenengineered with genes that make itglow or express a protein in its milk?When does the use of biotechnology

on animal bodies step over an ethicalline, or are their bodies open platformsfor our biomechanical tinkering?The conflict becomes clear in cases

such as the experiments of SanjivTalwar and John Chapin and their col-leagues at SUNY, who wired rats withelectrodes in their sensorimotor cortexand again in their pleasure centers(medial forebrain bundle), and thencontrolled the rats movements by stim-ulating them to turn right or left as the

experimenter desired.2 Animal rightsgroups and ethicists often complainedthat these animals were denied theirautonomy, turned into “ratbots” or“roborats.” Even Sanjiv Talwar admit-ted that the “idea is sort of creepy.”3 Yetwe use animals for work and recreationpurposes every day in ways that signif-icantly restrains their autonomy,whether they are drug-sniffing dogs orplow oxen or aquarium dolphins orcanaries in a cage. Are roborats reallyany worse off? Clearly, from an ethical perspective,

the suffering of animals in general doesnot free us from the obligation to treatour animals ethically in the laboratoryor biotech industries. So what is wrong

with the roborat? The difference between robo-rats

and drug-sniffing dogs, for example, isthat in the case of the dogs, they aretrained to exhibit certain behaviors,then rewarded with affection or foodfor those actions. They are taught tounderstand, and are rewarded forunderstanding. Dogs unable or unwill-ing to conform are not used as workdogs. The robo-rats, on the otherhands, do not really understand whatthey are asked to do, and the rewards,delivered directly to the brain, do notconform to the nature of rewards wegenerally expect to give animals—food,for example—which connect an under-standable action to a primary biologi-cal function, in the hands of a recog-nizable human master. The robo-ratdoes not understand the behaviorbeing asked and does not participate in

the reward being offered, and it has nopotential relationship to the master. Allis done remotely, both request andreward, through impulses sent directlyto the brain. In that sense, the robo-ratis instrumentalized beyond the pet orwork animal, and is denied a level ofautonomy given even to farm animalsand caged pets. The violation in thecase of the robo-rat is taking that laststep: removing all relationship with theanimal and truly treating it as a mech-anism to be controlled rather than aliving creature.The lines are not clear, and the stan-

dards shift with time and place. As webegin to create animals whose verybodies are pharmaceutical manufac-turing plants, whose organs provide

life-saving transplants, andwhose bodies have alteredgenetics and physiology to pro-vide experimental platforms forour science, we have to scruti-nize our motives and ouractions. Animals are both commodi-

ties and autonomous beings,and in order to maintain ourrights to consider them as theformer, we are obligated at the

same time to honor the latter. Clearly,there is a certain amount of self-con-tradiction involved. We do not treat allanimals the same, and we have differ-ent standards even for the same animalin different contexts. Our pretenses,however, do not absolve us of our ethi-cal responsibilities. As we create newways to integrate biotechnologies intoanimal bodies, we must constantlyrevisit and redefine the line betweenthe use of animals and their exploita-tion, the control of behavior and theirright to a certain level of autonomy,and the instrumental use of animals forthe general welfare and the manipula-tion of animals for our curiosity orentertainment. There may be no bettermeasure of our humanity than how wetreat our animals.

Paul Root Wolpe, PhD, is Professor ofBioethics and Director of the Center forEthics at Emory University.

VoluMe 24 NuMber 2 GeNeWatch 5

be subjected to if the GE salmon weredefined as “food.” Yet the salmon’srecombinant DNA makes for a poordrug, as - it does not appear to provideany benefit to consumers or the envi-ronment. Like trying to fit a square peginto a round hole, the FDA is trying toforce a genetically engineered foodproduct into a regulation written fordrugs.Using the New Animal Drug (NAD)

process to approve GE animals is alsoinappropriate, as it only compares therisk of GE salmon compared to eatingnon-GE salmon. The process fails toproperly look at the major impact GEsalmon will have on the environmentor human health. It does not look atthe impact GE salmon farming willhave on fishing communities or theimpact expanding use of GE salmonwill have on the production and con-sumption of these fish. The NADprocess does not require a proper cost-benefit analysis, nor does it look atalternatives to using GE fish entirely.At the heart of the issue, the NADprocess fails to look at GE salmonapproved for food as food and slyly

The environmental dangers posedby the FDA’s approval of geneticallyengineered salmon for human con-sumption were highlighted in the fallissue of GeneWatch.1 Unfortunately, awhole herd of genetically engineeredanimals are in the works. If we do notfix our inadequate regulatory systemnow, we could face a host of irre-versible risks in the future. In the U.S., the process of regulating

biotechnology comes from the“Coordinated Framework forRegulation of Biotechnology,” whichwas created in 1986 to preventbiotechnology-specific regulationsfrom being written. In their place,agencies were asked to use currentrules and find ways to apply them tobiotechnology products. The coordi-nated framework also designateswhich U.S. agencies will oversee whichproducts. For example, the USDAapproves genetically engineered (GE)crops before they can be planted, whilethe FDA governs GE crops once theyleave the farm. The FDA also regulatesGE animals for the production of foodand pharmaceuticals. This has led to

an absurd status quo, with FDAapproving GE animals not as newfoods, but as new animal drugs. The FDA defines a “drug” as some-

thing that is intended to affect an ani-mal’s structure or function. For GEanimals, recombinant DNA (the engi-neered genes) qualifies as a “drug”under the FDA’s definition. It isimportant to note that in the case ofGE salmon, this “drug” does notimprove the health of the salmon orthe people consuming it. In fact, therDNA construct that produces growthhormone year round is responsible fora number of adverse effects, such asjaw erosion and other physical abnor-malities in the salmon, the potentialfor increased allergenicity amonghuman consumers, and lower ratios ofOmega-3 and -6 fatty acids in themeat—even though the presence ofthese healthy fats is one of the primaryreasons many people choose to eatsalmon in the first place.The only reason GE salmon is being

proposed as a “drug” is to allow thecompany that produces it to avoid themore stringent regulations that it may


Food and Drug Amalgamation

The FDA is readying to approve genetically engineered salmon ... as a “drug”

BY ERIC HOFFMAN

tries to get these fish onto our plateswithout the proper precautions orenvironmental review. While this “frankenfish” is unsettling

to most Americans (91% of whomdon’t want this fish to reach theirplates), the trouble with GE animalsdoes not end there. The same compa-ny that is marketing this GE salmon,AquaBounty Technologies, also hasGE tilapia and GE trout waiting in thepipeline for approval. Another compa-ny, Hematech, is working on GE cowsthat theoretically cannot get mad cowdisease, which begs the question: Is itreally easier to alter the genome of acow to stop producing prions in itsbrain than to simply stop feeding cowsdead animal brains (which is how madcow disease is spread)?Other companies are looking into

developing GE chickens that areunable to transmit bird flu, and recentreports from China revealed thatresearchers have created a GE cow thatmakes “human breast milk” instead ofcow milk. And of course there is the“Enviropig” from a Canadian universi-ty, a transgenic pig that produces lessphosphorus in its waste—allowingindustrial animal factories to shoveeven more pigs into their tightly con-fined feedlots while continuing to pol-lute as much as they do today.If the FDA approves the GE salmon

for human consumption, it will openup a floodgate of GE animals onto ourplates—and it is likely GE food prod-ucts will not even be labeled as such.These approvals will all happen underthe illogical regulatory framework ofapproving GE animals for food as “ani-mal drugs” and not the foods theytruly are.So where are we now? The U.S. Food

& Drug Administration’s VeterinaryMedicine Advisory Committee held apublic hearing on the approval of GEsalmon last September. Since then, theFDA has remained silent on the issueas it finalizes its EnvironmentalAssessment, which will be posted for a30-day comment period sometimesoon (and will likely be completelyinadequate).2 Approval will shortlyfollow this Environmental Assessmentif the FDA does not find any signifi-cant environmental harms.Since the FDA’s hearings on the GE

salmon, two federal bills were intro-duced in both the House and Senate bySenators Mark Begich (D-Alaska) andLisa Murkowski (R-Alaska) as well asRepresentative Don Young (R-Alaska).These bills would ban the approval ofGE salmon or require labeling if the

fish is indeed approved. The currentlegislation proposed in Congress isimportant but the bills, if passed, areonly a temporary fix for the largerproblem of a completely inadequatesystem surrounding GE animal regula-tion.What would the proper oversight of

GE animals look like? Below is an out-line of what regulations on GE animalsthat protect human health and theenvironment would entail.Legislation on the approval, use, and

commercialization of genetically engi-neered animals must:1. Encompass all GE organisms for

human or animal food, or food andfeed containing GE organisms.2. Require independent and compre-

hensive risk assessment of GE organ-isms, including: - Analysis of the engineered genes

and their long term stability over mul-tiple generations;


“If the FDA approves the GE salmon for human con-sumption, it will open up a floodgate of GE animalsonto our plates—and it is likely GE food productswill not even be labeled as such.”

- Safety of eating the GE animal orproducts from the GE animal;- Comprehensive and independent

environmental impact reviews, includ-ing whether approval of any animalwith a wild relative that lives in orcould ever enter US jurisdiction;- Assess the economic harms likely

to be caused by any approval; and - Assess the health and welfare of all

GE animals over the lifespan of theanimals.3. Require labeling of GE animals

for:- All products intended for human

or animal consumption that have beengenetically engineered;- Any foods containing any amount

of GE product; and- The creation of a tracking system

of GE animals and products throughthe food supply.4. Mandate transparency in the

approval process with adequate timeand ability for public participation.3

Until such regulations are put inplace, all decisions on the approval ofGE animals for food must be stopped.Our current way of regulating GE ani-mals as “new animal drugs” is nonsen-sical and does not require the properanalysis of risks to human health, theenvironment, the health of wild-typepopulations related to the GE animals,the economic impact these GE animalsmay have, or the level of transparencyneeded to guarantee a reasonable levelof public participation in the decision-making process. Contact your members of Congress

today and ask them to co-sponsor HR520 and HR 521 (in the House ofRepresentatives) and S 229 and S 230(in the Senate) to stop the approval ofGE salmon or require that these fish belabeled if approved.

Eric Hoffman is Biotechnology PolicyCampaigner at Friends of the EarthU.S.

april-May 2011

biotherapeutics (such as pharmaceuti-cal proteins from sheep’s milk, first atRoslin Institute in 1989); could poten-tially develop into future organ donors(usually attempts at pigs modified togrow specific organs compatible fortransplant into humans); and evennovelty pets (starting with the fluores-cent GloFish). This period also marks when

researchers began attempting to applygerm-line engineering to improve ani-mals’ food production. Unlike othertypes of transgenic technologies, mostof which aim to adapt animals fornovel uses, attempts to upgrade live-stock-based food production throughtransgenics pits genetic engineeringagainst the time-tested mechanisms ofselective breeding that had graduallyhoned those same characteristics overmillennia. Humans have been develop-ing specialized varieties of sheep for atleast six to eight thousand years,selecting for some of the same traits—fast growth rates, feed conversion effi-ciency—that the Roslin Institute hastried, mostly in vain, to improvethrough genetic engineering.Meanwhile, when other researchers

at Roslin began engineering transgenicsheep that produce biotherapeuticproteins in their milk, they wereattempting something that couldn’t bedone through conventional methods.And unlike bioengineered food ani-mals, “pharming” reached the marketand is being adopted in new forms.GTC Biotherapeutics (see page 11)was the first to get regulatory approvalfor a pharmaceutical produced by atransgenic animal with ATryn, anantithrombrin derived from the milk

of transgenic goats. Other companieshave since developed goats, cows, andeven rabbits that can produce varioustherapeutic proteins in their milk. Theend product may not be novel, but themeans certainly is. Most of the bio-therapeutics being produced throughanimal pharming are already commer-cially available through other produc-tion means, but the strength of pharm-ing is its potential to manufacture thesame product at a significantly lowercost. A few hundred of GTC’s goatscan produce as much antithrombrinproteins as a lab that costs millions ofdollars to set up and millions more toscale up.The same cannot always be said of

transgenic food animals. In manycases, germ-line engineering of a food-producing animal may be used toattempt to extend the aims of conven-tional breeding; in other words, toimprove food production. These traitscan be improved without genetic engi-neering, of course, and have been forthousands of years, but genetic inter-ventions can produce much moredrastic results—for better or worse.AquaBounty’s genetically modifiedsalmon grows far more rapidly than itsconventional counterpart, andalthough this “improvement” raises ahost of serious concerns (detailed byEric Hoffman on page 6), from a strict-ly production-oriented standpoint, itcould be a boon to some fish farmers(and certainly to AquaBounty). On theother hand, when the United StatesDepartment of Agriculture funded thedevelopment in the 1980s of pigs car-rying the human growth hormone inan attempt to create a faster growing,

8 GeNeWatch

Over 10,000 years ago, humansbegan to domesticate animals.Livestock—sheep, goats, and cattle inSouthwest Asia, pigs in current-dayChina—began to replace hunting asthe primary source for meat and skins.Humans found new uses for animals:collecting milk from lactating rumi-nants and eggs from poultry; harness-ing cattle, donkeys, and water buffaloto plows; shearing the wool fromsheep and alpacas; climbing onto thebacks of horses and camels for person-al transportation; and, of course, pro-ducing biopharmaceuticals using pro-teins extracted from the milk of trans-genic goats.If that last item sounds a bit abrupt

in the chronology of animal domesti-cation, that’s because it is. Even afterthousands of years of selective breed-ing, farmers and animal scienceresearchers in the 20th century foundplenty to improve upon. The establish-ment of new and enhanced livestockbreeds moved at an astonishinglyrapid pace, as developments thatmight have taken centuries wereaccomplished in decades. Yet, whilemodern farmers and researchers pos-sessed tools unavailable to their for-bears, they still relied on selectivebreeding to achieve genetic upgrades.In the 1980s, the advent of recombi-

nant DNA technology appeared toherald a new age in animal agriculture,allowing the engineering of specificgenes and selective introduction ofnovel traits. Scientists began creatingtransgenic animals that served as bet-ter lab subjects, (such as “knockoutmice,” engineered not to express a cer-tain gene); enhanced animal-generated

Food Unchained

Researchers are having a difficult time genetically engineering livestock to produce foodbetter than their non-engineered counterparts

BY SAMUEL W. ANDERSON


acid.

- In the 1990s, British researchersbegan attempts to develop trans-genic sheep resistant to scrapie, aprion disease similar to bovinespongiform encephalitis (or madcow disease), which is 100% fatal insheep. Research has also beenundertaken to develop cows resist-ant to mad cow disease, so far withno published success.

The prevailing flaw in these tech-

nologies—presuming they were suc-cessfully developed—is that while themethod may be novel, the result is not.A surprising amount of research ontransgenic food animals has been benton achieving what can already beaccomplished more gracefully throughconventional breeding, altered pro-duction practices, or human behav-ioral adjustments. In many cases, all ofthe time and money spent developinga new transgenic livestock breedserves only to replace an existing solu-tion, even if it is more efficient, effec-tive, and sustainable than a geneticallyengineered silver bullet.Take the above examples:

- “Enviropig” is awaiting approval forhuman consumption in Canada andthe U.S., and already has the greenlight from Canada’s Department ofthe Environment and the blessing ofswine industry groups. Yet, it repre-sents an incomplete solution (phos-phorous is not the only problemnutrient in pig manure) to a problemthat already has solutions at hand.Unfortunately, those alternatives—changing the pigs’ rations by addingan enzyme (phytase, which can

reduce phosphorous inmanure by over 50%) orusing different grains;being more careful andstrategic when spreadingmanure on fields as fertil-izer; and most of all, ditch-ing the vast 10,000+ hogconfinement operations infavor of smaller, diversi-fied farms—requirebehavioral changes in thehog industry, as opposedto maintaining the statusquo with new pigs.Enviropig has been framedby its creators and theswine industry as an envi-ronmental breakthrough,but from the perspective

of environmental protec-tion, it addresses a problem

that already had known solutions. Inreality, despite the name, Enviropigwas designed to solve hog industryproblems. It reduces the amountthat producers need to spend onmineral supplements, but moreimportantly, it allows the hog indus-try to appease regulators and scaleup operations without changing theprevailing practices.

- Iritani’s “Popeye pig,” with apparently20% of its saturated fat converted tohealthier unsaturated fats by aninserted spinach gene, never resur-faced after it was announced in2002. At the time, Iritani essentiallyadmitted that he did not expect the

leaner meat animal, the results yieldedonly a sickly litter afflicted with anarray of odd conditions, includingpneumonia, peptic ulcers, and arthri-tis. Of the 19 now-infamous“Beltsville pigs,” 17 died before reach-ing one year of age. These ventures may have resulted in

an animal welfare fiasco and the veryreal threat of a catastrophic disruptionof ocean ecosystems, but we can atleast see why they were carried out.The achievement—or intent, in theBeltsville pigs’ case—wasto more efficiently convertgrain to meat, doing sowith one radical improve-ment that may have takenmany years to accomplishthrough conventionalbreeding.Many other endeavors to

improve livestock foodproduction through germ-line engineering appearredundant or superfluous,which may explain theirtendency to either fail orfizzle out. Ironically, manyof these projects alsoreceive the most press, ifonly for their novelty:

- “Enviropig,” developed byresearchers at Ontario’sUniversity of Guelph, is able todigest a form of phosphorous in feedgrains that it would normallyexcrete, reducing the phosphorouslevels of its manure by 30 to 70%,with the aim of diminishing the envi-ronmental impact of large-scale hogproduction.

- Akira Iritani, a scientist at Japan’sKinki University, reported in 2002that his team was the first to suc-cessfully add a functioning plantgene to an animal, in the form of pigsthat carried a spinach gene. As aresult, Iritani said, the pigs’ carcassheld 20% less saturated fat, convert-ed by the novel gene into linoleic

A “Beltsville Pig”

pig to be commercialized due to lackof public acceptance; but he alsoexpressed his hope that “safety testswill be conducted to make peoplefeel like eating the pork for the sakeof their health.” The notion ofencouraging people to eat pork fortheir health may raise an eyebrow;beyond that, one need not think toohard to come up with simpler waysto cut down on saturated fat (trim itoff of your pork chop, or simpler yet,cut back on the meat).

- Attempts to engineer transgenicscrapie-resistant sheep appear tohave fallen by the wayside, presum-ably because many sheep alreadycarry a dominant gene for scrapieresistance, allowing producers, aftersending biopsies to a lab, to selectagainst scrapie susceptibility.Mandatory scrapie ID tags in theU.S. and other countries have alsohelped track and control the spreadof scrapie. The best argument thatconventional breeding and well-exe-cuted containment practices pre-empt any usefulness of transgenicscrapie-resistant sheep is their suc-cess: Australia and New Zealandhave officially eradicated the disease,and the U.S. has reduced it to 0.03%of the nation’s entire flock.Like transgenic scrapie resistance,

genetically altering cows’ genomesto grant them mad cow resistance isessentially a superfluous advance.While some research suggests thatgenes can influence mad cow resist-ance or susceptibility, the disease ismost often believed to be contractedwhen brain tissue from another ani-mal mad cow disease carrier (orscrapie, some studies say) enters intoa cow’s feed. In the U.S. and Canada,stringent steps to keep ruminant tis-sue out of ruminant feeds helpedessentially eradicate mad cow inNorth America—no transgenicinfluence needed.

Despite the headlines about cowsthat produce something akin tohuman breast milk or cattle genetical-ly engineered for immunity to sleepingsickness, the most marked shortcom-ing of transgenesis as a means ofimproving food animals is evidencedby the host of experiments that don’tmake headlines. Attempts to createhealthy, fast-growing transgenic sheepcarrying the human growth hormonebegan in the mid 1980s. In early exper-iments, the transgenic lambs grew ataverage rate until reaching 15 to 17weeks, at which point “over expres-sion” of the growth hormone resultedin two rather counterproductive sideeffects: “reduced growth rate andshortened life span.” Fifteen years later,growth hormone experiments in sheephad only managed to yield larger thannormal sheep. At 12 months, trans-genic rams were only 8% larger thanthe control rams, and with no signifi-cantly increased feed efficienciesnoted. AquaBounty’s success bringing

genetically modified salmon to marketis, so far, an anomaly; to date, no otheranimal has been commercialized car-rying a transgene that increases theamount of food it produces or the effi-

ciency with which it converts feed tomeat, milk, or eggs. Meanwhile, thegoats, cows, chickens, and even rabbitsthat have been developed to producehuman biopharmaceuticals are, insome cases, already proving to be themost economical producers of sometherapeutic proteins. Pharming is notwithout its drawbacks, and the need tocarefully test and regulate all productsof transgenic animals is evident.Nonetheless, if a genetically modifiedanimal is to deliver significant benefitsfor humans, there certainly seems tobe a surer path for those using geneticengineering to coax an entirely newuse out of an animal which has beenselected on the basis of its existingadvantageous traits; as opposed tothose projects taking on conventionalbreeding programs at their owngame—attempting, with a single trans-genic silver bullet, to outshine thou-sands of years of purposeful selection.

Samuel W. Anderson is Editor ofGeneWatch.


GTC Biotherapeutics was the firstcompany to bring a pharmaceuticalproduct to market which had beenderived from transgenic animals, usinggoats modified to produce therapeuticproteins in their milk. The product,ATryn (an antithrombrin) received reg-ulatory approval in the EU in 2006 andin the U.S. in 2008. Dr. William Ravis,DVM, is the chief veterinarian at thecompany’s Massachusetts farm.

How many goats does GTC cur-rently have on the farm? Do youthink of it more as a “farm” or a“lab”?While our facility in Charlton is

indeed a farm, it is a very unique andspecialized facility licensed by theappropriate regulatory agencies tohouse the goats and to produce humanrecombinant therapeutic proteins intheir milk. Currently, we have approxi-mately 600 goats on the farm.

After inserting the transgene intoearly stage embryos, what are yoursuccess rates getting live births andoffspring that carry the transgene?What happens to the offspring thatdon’t carry the transgene?We use more than one technology to

insert the transgene of interest, andwhile we do not disclose our successrates for those programs, we do feel wehave developed a certain expertise inthis area and have a (comparatively)high level of success.With regard to offspring that do not

carry the transgene, there are otherpotential uses for those animals withinour operations (such as use in breedingin future programs). We work very hard

to efficiently use animals within ouroperation.

How do you respond to concernsabout animal welfare in using goatsto produce biotherapeutics ratherthan, say, bacteria?We do not believe that there are any

animal welfare concerns inherent in theuse of goats for producing milk thatcontains a human recombinant thera-peutic. On the contrary, the goats atGTC are very well cared for and enjoysome benefits not found on a tradition-al dairy farm, such as full-time veteri-narian oversight and regular healthchecks.The bottom line is that we are main-

taining and milking dairy goats in avery similar fashion to how it is done inthe commercial goat milk industry –albeit with significantly more monitor-ing and documentation. The only dif-ference is that our animals have anadditional piece of DNA that affordsthem a unique ability to produce anadditional specific recombinant proteinin their normal milk production.With regard to comparisons to the

bacterial fermentation platform forbiologics (or other production systemsfor recombinant therapeutics), we atGTC feel that our system has a numberof significant advantages in compari-son. Not only can we produce a numberof molecules that bacterial fermenta-tion cannot, we can also produce ther-apeutic proteins in a very cost effectivefashion. As you are aware, the state ofour health care system begs for a capa-bility to produce medicines that willstart to bring down the cost of life sav-ing therapies. Lastly, there are at timessignificant limits to alternative produc-tion systems that impact the availabilityof these medicines and therefore limittheir usefulness to the general popula-

tion that might need them. Our systemof production has clearly shown a sig-nificant ability to produce large quanti-ties of these medicines that could meetthe current unmet medical needs formore patients

Do you see transgenic dairy goatsas the ideal production method fordrugs like ATryn? Is there a “nextstep” from here, or is it just a matterof tweaking the system you alreadyhave in place?In the case of antithrombin/ATryn,

yes, we believe that the product is bestsuited for the goat. Our next steps fromhere are always looking for improvedefficiencies across the whole processbut we will be staying with the goats asthe production species. Additionally,we will be exploring unmet needs forthis product through the developmentof new indications that have not beenpreviously explored, possibly due tolimited supply or perhaps over safetyconcerns of the risks of blood-bornepathogens, for the competing plasma-derived alternative that is currently onthe market.

As you develop your breeding herd,what qualities do you select for tomold the perfect human-protein pro-ducers?The attributes that we look for are

what you might look for in any com-mercial dairy operation across thecountry. We look for those goats thatpass on superior dairy genetics withregard to daily volume of milk produc-tion as well as overall length of lacta-tion. Additionally, all dairy animalshave slight variability that impact theproteins found in their milk, so we alsoselect for goats with optimal proteinproduction.


Goat Pharming

An interview with William Ravis, chief veterinarian at GTCBiotherapeutics

BY CRG STAFF

continued on page 15

About a decade ago, I had the greatpleasure to spend some time in the stu-dio of a well-known New York Cityartist who was interested in the thenburgeoning and often over-publicizedscience of genetic modification of ani-mals and plants. This inquisitive artist was Alexis

Rockman, a painter with a reputationamong his colleagues for paintings“depicting nature and its intersectionswith humanity,” and “painstakinglyexecuted paintings and watercolors ofthe phenomena of natural history.”The interaction was as timely as it

was interesting. Alexis knew little

about the techniques of genetic modi-fication or genomics, but was— andcontinues to be—a superb natural his-tory artist. Meanwhile, I had just begunto curate an exhibition on the humangenome and genetic technology at theAmerican Museum of Natural Historyentitled “Genomic Revolution.” Thus


Back on “The Farm”

The story behind an iconic painting and its vision of the future, a decade later

BY ROB DESALLE

“The Farm,” reproduced with permission of Alexis Rockman

began our relationship: an artist and ascientist talking every Thursday after-noon about genetic technology overcoffee in his studio.Some of the topics that Alexis want-

ed to discuss seemed pretty bizarre.However peculiar the topic, I wouldfirst try to explain the technology toAlexis and then would add an extralayer of science once we felt comfort-able with the primer and its jargon.Throughout this process, it becameimmediately obvious to me that as hewas soaking up the material, Alexis wasworried that some of the geneticallymodified versions of animals wouldimpact our natural world. After about two months of my

genomics “tutorial,” Alexis dismissedme and began work on a piece of art hewas later to call “The Farm.” I left thelast meeting with some apprehensionabout the art that might come from ourconversations. While I felt that Alexispossessed a firm general understand-ing of genetic technology, I was— andcontinue to be— wary of how an artistor an author might take creative licensewith science. While walking in the SoHo neigh-

borhood of New York City one fall dayin 2000, I looked up at a huge billboardat the intersection of Lafayette &Houston Streets. The billboardstunned me. Erected by an organiza-tion called DNAid, it featured Alexis’“The Farm” in all of its glory. Since Ihad only seen sketches of some ofAlexis’ ideas, I was blown away by theimmensity of the piece, by its vividnessand candor. Through his strong under-standing of natural history, Alexisstrove to create an awareness about theexistence of plant and animal ancestralforms among his audience. Morespecifically, Alexis wanted his audienceto understand that all living organ-isms—not just plants and animals—have ancestral forms. To facilitate thisunderstanding, Alexis painted certaindomestic animals while including the“ancestral” versions of them. Hence, wesee chickens, swine, cattle, wild mice,and domestic crops in the backgroundof the painting. It is purposefully ironicthat each of these domestic forms has

its wild form that existed probably atmost 20,000 years ago, when domesti-cation began. In the foreground, a slew of geneti-

cally modified organisms lurk near abarbwire fence. All of these peculiarcreatures came from Alexis’ thinkingabout the extent and limits of geneticmodification. The painting includes aninteresting menagerie with plants, suchas tomatoes, grown in cube-likeshapes; a mouse with an ear growingoff of its back; a rather porcine pig withhuman organs growing inside it; and alarge cow I can only describe as“Schwarzeneggerish.” As bizarre as thepainting’s modified organisms look,they were, as Alexis suggests in thedescription that accompanied thepiece, informed by reality. I thought it might be interesting to

look at these four modified organismsa decade later to see how well-informed the artist was in drawingthem and what their status is now. Let’sstart with the geometrically bizarredomestic plants. I recall from our con-versations that Alexis was alreadyaware of “Flavr Savr,” one company’sattempt to genetically modify tomatoesto maintain freshness, but he was par-ticularly taken aback by the possibilityof genetically modifying things tochange their shape. The square toma-toes in “The Farm” would be muchmore easily and efficiently packaged.Alas, Flavr Savr went bust around thetime Alexis produced the piece, and tomy knowledge no genetically modifiedcube tomato has been produced.Perhaps the most peculiar animal in

the piece is the mouse with a humanear attached to it. I recall that Alexisand I had discussed the potential ofusing non-human animals as culturingmedia for human organs. In 2000, thisidea was very prevalent in the news, soI didn’t label this fascination as“bizarre”; rather, I thought that hisquestions about the topic were timelyand warranted. In fact, the pig with thehuman organs growing inside it wasalso a popular news story at that time. The “earmouse” (also known as the

Vacanti mouse) actually did not have ahuman ear growing out of it. The “ear”

consisted of a gob of cow cartilagegrown in the shape of an ear. It wasproduced not by genetic engineering,but by inserting a polyester fabric thathad been soaked with cow cartilagecells under the skin of an immunocom-promised mouse. Pigs as donors ofhuman organs, meanwhile, are some-thing we may see in our lifetime. Somepig organs, including their hearts, areabout the same size and have the samegeneral plumbing as human organs,and scientists have suggested that pigsmight be a good source of organs forhuman transplants. Like any transplan-tation, though, tissue rejection is animportant consideration, and somegenetic modification of the pigs toovercome rejection would be needed.While this might seem farfetched—especially when Alexis produced “TheFarm,” over ten years ago—the possi-bility has been resurrected as a resultof work in 2009 in China producing pigstem cell cultures. Such cultures can beused as an easier method to geneticallymodify pigs to circumvent the rejec-tion problem. A year later, Australianscientists genetically modified a line ofpigs by removing a stretch of a singlechromosome in order to alleviate therejection problem and allow experi-ments with lung transplants to pro-ceed. The last animal in Alexis’ menagerie

is the Incredible Hulk Cow. “Double-muscled” cows do exist, such as theBelgian Blue and the Piedmontese.These breeds have a defective myo-statin gene which would otherwise,when expressed normally, slow musclecell growth in a developing cow.However, these breeds came aboutthrough conventional breeding, notgenetic modification. To my knowl-edge, super-muscular cows have notbeen successfully engineered, althoughresearchers are working on severalother bovine genetic engineeringtricks, including cows with alteredgenes to improve the conversion ofmilk to cheese or engineered for resist-ance to mad cow disease.While only one of the bioengineered

animals in Alexis’s menagerie stillexists today—pigs being developed as


continued on page 23


Top left: A fruit fly geneticallyengineered to grow only oneeyeTop right: The “Vacanti Mouse,”an immunocompromisedmouse supporting an earformed from cow cartilageLeft: A flourescent piglet (left)alongside a normal oneBottom left: ANDi, a rhesusmonkey engineered to glowunder a UV lightBottom right: Dolly, the firstcloned sheep


pation in the case. Plaintiffs urged thatseveral individuals and groups haddemonstrated sufficient likelihood ofinjury to confer standing. The panelexpressed some concern that such afinding might allow any customerwanting access to a cheaper product tobe able to challenge a patent. Turning to the merits, the panel

entertained arguments from both theU.S. government as represented by theSolicitor General (the US Governmenthad earlier filed a friend-of-the-courtbrief asserting that patents issued bythe PTO covering isolated DNA areinvalid), as well as from representativesof the litigants. The Solicitor Generalasked the judges to imagine a magicmicroscope that would allow them togaze into and through everything innature, arguing that no company canlegally claim ownership over anythingseen though such a lens. The ACLUattorney noted that isolation cannot bethe test for patentability declaring:

If a surgeon cuts me open, andslices out my kidney, and takes itout and holds it in his hand, it’s an‘isolated’ kidney, but it’s still a kid-ney. It’s not an invention.

Myriad’s attorney argued that isolat-ed DNA has never existed in nature,that it is a product of human ingenuity,and therefore it satisfied thepatentability test. Judge Bryson asked

him:

To me, at least, it is an importantquestion as to how preclusive yourpatent—and any other patent onany particular gene—would be if,in effect, you have to get 100, 200or 1,000 licenses before you cansequence the genome of an individual.

The judges generally struggled toidentify any kind of patent eligibilitytest. Patentable compositions of mattermust be different in kind from thosethat are naturally occurring. JudgeLourie, who appeared the leastimpressed by the ACLU’s claims, camethe closest by exploring a test centeringon whether covalent bonds are broken.He noted that breaking those bondschanged the composition of an isolatedstrand of DNA from its counterpart inthe human body. The ACLU arguedthat isolated DNA is identical to DNA,and stated that all Myriad did was “snipthe gene.” Judge Lourie reined in thatargument, arguing that isolating DNAwas “not research by tweezers.” How the court will actually rule is

impossible to predict, but an opinion isexpected by late summer. Whicheverway the court does rule, it is a certain-ty that the losing party will appeal tothe Supreme Court for a final determi-nation.

topic update

Federal Circuit Hears Appeal in Myriad Gene Patent Case

In front of a packed courtroom onApril 4th, the Court of Appeals for theFederal Circuit heard arguments inAssociation for Molecular Pathology v.USPTO. This potential landmark casein patent law challenges the patentsheld by Myriad Genetics, a biotechnol-ogy company, on two human genesrelated to breast and ovarian cancer.The American Civil Liberties Unionand the Public Patent Foundation filedsuit in 2009 on behalf of researchersand women claiming that such patentswrongly restrict science and make itdifficult for women to gain vital med-ical care (CRG has filed an amicus briefin the case). During the past 30 years,the U.S. Patent and Trademark Officehas issued more than 50,000 patentsrelated to genes in humans, animals,plants, bacteria and others. A finalopinion in the Myriad case could likelydetermine whether patents connectedto naturally occurring genes can begranted by the federal government. Before reaching the merits of the

arguments, the three-judge panel spenta significant amount of time exploringthe procedural question of whetherthey had jurisdiction over the case—specifically, whether the plaintiffs haddemonstrated that they had standingto sue. U.S. law requires that the partiesto an action have a sufficient connec-tion to and harm from the action chal-lenged to support that party’s partici-

As GTC and other companies scaleup production herds, are there likelyto be opportunities for independentfarmers to start their own herds ormanage a contract operation, or arecompanies more likely to keep pro-duction confined to their own securesites?Due to the rigors imposed (e.g. exten-

sive and on-going documentationrequirements) by regulatory authori-ties, we believe that it is highly unlikelythat these activities will be contracted

out to independent farmers.

What other techniques or productswould you consider to be “the com-petition?”As you mentioned, cell-based fer-

mentation production technologies arecurrently used for the production ofmany therapeutic proteins.Unfortunately, that technology is a veryinefficient system for many proteins,unable to produce other proteins, andwhere it is employable it does not offer

the “scalability”—the ability to increaseproduction easily and inexpensively—of transgenic mammary gland proteinproduction.GTC has an issued U.S. patent broad-

ly covering the production of therapeu-tic proteins in the mammary glands ofmammals until 2027, and thus does notforesee any near-term direct competi-tors.

continued from page 11

Within a matter of weeks in early2003, severe acute respiratory syn-drome (SARS) spread from theGuangdong province of China to rap-idly infect individuals in some 37 coun-tries around the world. The brief epi-demic infected more than 8,000 peopleand killed nearly 800, almost 10% ofthose infected. Fortunately, timely pub-lic-health actions, such as isolation ofvictims, stopped SARS before itbecame a world-wide epidemic. It isgone from nature, at least for now. Wedodged a world-wide epidemic. But SARS lives on, imprisoned in

BSL3 and BSL4 laboratories around theworld, and has already escaped morethan once through infected lab work-ers. If we experience another SARSepidemic, many scientists feel that itwill have started from a laboratoryescape. An escape of a highly contagious

pathogen from a lab in a city is morelikely to seed an epidemic; and thistime, we may not be able to dodge it.What if a lab researcher is infectedwith a highly contagious deadly diseasethat is transmitted by casual contact, avictim’s cough or from contaminatedsurfaces? Besides SARS, the 1918 pan-demic flu also comes to mind. TheBoston University National EmergingInfectious Disease Laboratory likelywill research SARS and the 1918 pan-demic flu. Under the reasonable assumption

that employees tend to live near wherethey work, the probability of an epi-demic would be far greater from aninfected employee living and workingin or near Boston. For instance, thenumber of casual contacts withstrangers will be sizeable for an infect-ed researcher taking public transporta-tion, a likely way to commute.Transmission of infection to others,

called secondary infections, would bealmost impossible to trace. For a labo-ratory located in the suburbs or ruralarea, most employees would drive, sotheir daily casual contacts withstrangers would be fewer, and there isat least some chance of tracing othersexposed. Tetra Tech, a world-wide consulting

firm, was hired by the NationalInstitutes of Health to carry out yetanother risk analysis for the BUNEIDL. The analysis is in progress.This is BU’s third attempt at a believ-able risk analysis for their lab. It isworthwhile to review the history of riskassessments for the BU lab. Attempt number one: This 2004 risk

analysis considered only one accidentscenario and only one pathogen, asmall anthrax spill in the laboratory. Anumber of lawsuits brought by resi-dents of Roxbury, the largely African-American Boston neighborhood andthe site of the NEIDL, challenged thecertification of the risk analysis by theMassachusetts’ Executive Office ofEnvironmental Affairs (EOEA). In2006, a Superior Court judge deemedthe certification “arbitrary and capri-cious” and ordered the BSL4 laborato-ry not to open until an acceptable riskanalysis was carried out.Attempt number two: The NIH then

set out on its own risk analysis, whichit unveiled in 2007. The analysis wascomprised of fifteen pdf files—withdozens of photographs, drawings,graphs and statistics—that gave theimpression of a precise and effort-laden risk analysis. But it takes only aquick scan of the many files to realizethat the whole analysis was set up togive the answer BU wanted, namelythat the inner city Roxbury location forthe lab was acceptable, not only accept-able but the safest location for the lab-

oratory. Here is how NIH reached this sus-

pect conclusion: As ordered by theSuperior Court, they did consideralternative sites in Massachusettsbesides densely populated Roxbury,namely Tyngsborough (a BU-ownedsuburban site) and Peterborough (aBU-owned rural site). The deadly andcontagious viruses chosen for theanalysis were ebola, sabia, monkeypoxand Rift Valley fever. These choicesaddressed another criticism of the firstrisk analysis that no contagiouspathogens were considered. (Anthraxis not contagious.) So far, all fine andgood. These are all “exotic” viruses (to use

the NIH terminology) but represent nopresent or likely future public-healththreat to the United States. The onlyscenario that NIH chose to analyze wasa single researcher infected at workwith one of the four exotic viruses, andthen bringing his/her infection home.The viruses are only mildly contagious,so intimate contact is required fortransmission. Symptoms appear quick-ly so patients can be diagnosed andprecautions taken, unlike theHIV/AIDS virus that can silently infectlarge numbers of victims without any-one being aware. Since the viruses would likely infect

only family members, health careproviders and others in intimate con-tact with the initial victim, the numberof secondary infections would be simi-lar no matter where the victim lives orworks, so population density at the vic-tim’s home or laboratory workplacewould not much matter. NIH askedonly the question that would give themthe answer they wanted. Location isnothing, to reverse the common real-estate mantra. But how does urban Roxbury


SARS in the City

How is it decided that an urban center is the safest place to house a deadly, highly contagious pathogen?

BY LYNN C. KLOTZ

become the safest site? The answer liesin Rift Valley fever virus, which istransmitted by mosquitos from cattleand other farm animals to humans.Even though many of Boston’s streetswere laid out by cattle in colonialtimes, there are no cattle there now. SoRift Valley fever virus would infectmore people in suburban or rural set-tings where farm animals live. UrbanRoxbury then becomes the safest placefor the NEIDL compared to suburbanand urban locations. Between the first and second risk-

analysis attempts, Massachusettschanged governors from Mitt Romneyto Deval Patrick and the managementof EOEA changed as well. The newEOEA folks made a smart move. Theyrealized that they did not have thebackground to understand the issues,so they asked the National Academy ofSciences to appoint a NationalResearch Council (NRC) committee ofexperts to critique the risk analysis.The NRC committee delivered theirdetailed critique in late 2007, conclud-ing that the NIH analysis was notsound and credible, that the worst casescenarios had not been adequatelyidentified, and that the informationunderlying the alternative site analysiswas insufficient or inappropriate. Thecritique also questioned the infectiousagents selected. Now back to the in-progress Tetra

Tech risk analysis. Tetra Tech present-ed its preliminary results to local resi-dents at the Roxbury CommunityCollege in October 2010. Among itsfindings was that a secondary infectionof SARS to someone outside the labfrom a lab researcher would occur

once in 10,000 years in a worst-casescenario, and likely only once in over amillion years. Tetra Tech looked atonly two scenarios, a centrifuge acci-dent and a massive earthquake thatwould level the laboratory. They didnot look at the risk of a SARS-infectedlab worker, unaware he/she was infect-ed, transmitting the infection to some-one outside the laboratory. The NRC committee commenting

on the Tetra Tech preliminary workconcluded “at this point in time it can-not endorse the illustrative analysespresented as scientifically and techni-cally sound or likely to lead to a thor-ough analysis of the public health con-cerns previously raised by the NRC.”The committee also noted“Consideration of the available casestudies (such as the SARS casedescribed below) suggests the possibil-ity that transfer of a pathogen outsidethe laboratory by an infected worker isan important class of risk events.”There have been at least three SARS

escapes from laboratories throughinfected lab workers. The incidentfrom the NRC 2010 document quotedbelow warns of the danger of a futureSARS escape in a densely populatedarea.

“In China, SARS/CoV was grownin a BSL-3 laboratory by a workerwho apparently had worn inappro-priate personal protective equip-ment (PPE) and then treated thesample to inactivate the virusbefore removing it to a BSL-1 lab-oratory for further work on theopen bench. The worker failed toverify the complete inactivation of

the virus and subsequently becameill and was admitted to a fever hos-pital. The laboratory was not noti-fied of this development and theworker later returned to the labo-ratory. A second worker who han-dled the “inactivated” sample alsobecame ill. A graduate studentwho observed the laboratory pro-cedure later traveled by train to herhome several hundred miles away.After returning to the laboratoryshe became ill and once again trav-eled to her home by train whereher mother, a physician, admittedher to a hospital and treated her.The student was asked if sheworked with SARS/CoV (she saidno because her research involvedanother virus). It was not until themother became ill and died thatSARS/CoV was identified. Otherlaboratory workers also became illand other hospital personnel died.This case study illustrates severalimportant points: people makemistakes (improper PPE); noteveryone follows procedures (fail-ure to test sample for inactivity);people may die if not properlydiagnosed and treated.”1

Another message from this story isthat research on deadly, highly conta-gious pathogens should be conductedonly in BSL4 laboratories in isolatedlocations where extra precautions inaddition to location are available, neverin a populated area since SARS has alsoescaped from a BSL4 laboratory.How many bites of the apple will

Boston University have before theyrealize that a BSL4 Laboratory indensely populated Boston is a bad anddangerous idea? When will the city orstate step up and say “No! No BSL4 labin Boston,” following Cambridge’s lead?

Lynn C. Klotz is co-author ofBreeding Bio Insecurity: How U.S.Biodefense Is Exporting Fear,Globalizing Risk, and Making Us AllLess Secure. He is working with scien-tists and Roxbury residents to proposean alternative vision for the BostonUniversity labs.


construed involving a whole organismif a commercial or business activityinvolving an organism with a patentedgene or cell necessarily involves usingthat patented part. This decision seemsto conflict with the earlier oncomousedecision against patent protection ofthe entire mouse.These cases reflect an as-yet-unre-

solved debate and societal tensionregarding biological, ethical, economic,and political aspects of human inter-ventions involving life forms in Canada.Arguments have sometimes alluded toextra-legal effects on capital invest-ment and international economic com-petitiveness, at times at the expense ofsound legal reasoning.7 It should benoted that in both cases, the SCCrejected the broad, carte blanche typeof whole organism patenting granted inthe United States. However, as a resultof the Schmeiser vs Monsanto decision,the legal status of whole organismpatenting in Canada lacks clarity on thebasis of such inconsistent case judg-ments by the highest court of the land.In the meantime, the momentum to

commercialize genomic research con-tinues unabated in Canada and else-where. Our knowledge of the full com-plement of genes of a growing numberof whole organisms is growing rapidlyand whole genomes are now beingreconstructed through synthetic biolo-gy techniques. Research melds withcommercial ventures through increas-ing university/industry collaborations.Despite these developments, thereremains no practical guidance forresearchers and policy-makers on theethical implications of privatizationand commercialization of bioresearchbeyond the general ethical frameworkof the Tri-Council Policy Statement.8 Inrecent qualitative studies, researchershave expressed more concern overincreasing secrecy, publication delays,and increasing numbers of material


The recent decision by United StatesDistrict Court Judge Robert Sweet toinvalidate seven patents on the BRCAbreast cancer genes held by MyriadGenetics is a monumental decision(though the decision is being appealedas expected).1 Coupled with the subse-quent U.S. Justice Department amicusbrief arguing against the patenting ofnaturally-occurring genetic material,2these events have triggered advocacygroups from other countries such asAustralia to consider its own legalaction to restrict DNA patentabilitylaws and policies.3 The pendulum nowmay be swinging away from interna-tionally-accepted, broadly interpretedand applied gene patenting practicestoward tighter rulings against thepatenting of naturally-occurring genet-ic material.4 In this changing climate,we offer a perspective on the currentstate of gene patenting in Canada.The case of the Harvard oncomouse

put Canada front and centre in genepatenting law and policy-making.United States patent approval for exclu-sivity rights to the oncomouse wasgranted in 1988. After eight years ofgovernmental and legal reflection anddecisions, at the end of 2002 theSupreme Court of Canada (SCC)denied the patent on genetically-modi-fied (GM), entire non-human mam-mals including the oncomouse by thenarrowest of margins.5 The five judgemajority argued that a mouse does notqualify as a “manufacture” or “composi-tion of matter,” the terms used in patentlaw for patentable materials.However, only a year and a half later,

in the case of Schmeiser vs Monsanto,the SCC ruled by the same narrow 5-4margin that a patent protecting com-mercial rights to GM cells in canolaplants also could impart de facto exclu-sive rights over the entire plant.6 Themajority argument hinged on the con-cept that patent infringement could be

Gene Patenting in Canada

From the oncomouse to cancer gene testing and beyond

transfer contracts than over patenting,commercialization, and conflicts ofinterest.9,10

Societal Imperatives: HealthcareAccess versus PrivateCommercialization of HealthcareResourcesIn Canada, the narrow margin of

SCC decisions of the above cases maynot only reflect discordant legal viewson patenting life forms but also ongo-ing societal differences of worldviewsover the relationship of humankindwith the natural order. In the past, TheCanadian Council of Churches and theEvangelical Fellowship of Canada haveargued that higher life forms should notbe patentable on the grounds thathumankind has a God-given responsi-bility to care for the created order.11 Inthis worldview, privatization and com-mercialization of life forms threatensthat overarching mandate. The recentparadigm-changing decision to strikedown the Myriad patents on naturally-occurring breast cancer-associatedgenes suggests that such a view may beregaining support at the highest gov-ernment and societal levels in the US(as suggested by the amicus brief notedabove), the country that granted thebroadest patent protection for theoncomouse patent. Notwithstanding the seemingly con-

tradictory judgments by the SCC overwhole organism patenting, the recentdrama played out over the Myriadpatents has somewhat ironically posi-tioned Canada as an advocate against“natural” single gene patenting. Unlikethe oncomouse and GM canola cases,however, the Myriad case impacts onpublic healthcare access to necessarydiagnostic testing, bringing a new andmore ominous societal danger to theconcerns over ‘anti-commons’ issues inCanada.12 It also brings into sharperfocus the societal and political forces

BY JAMES J. RUSTHOVEN

AND THE BIOTECHNOLOGY REFERENCE GROUPOF THE CANADIAN COUNCIL OF CHURCHES


that drive arguments for the variouspositions. Legally, in the judgment ofIndustry Canada’s Patent OfficeDirectorate, Myriad Genetics did notviolate Canada’s patent or competitionlaws.13 Industry Canada even chal-lenged the government of Ontario toprovide evidence that gene patentsdeterred research as well as evidencethat it could not obtain a compulsorylicense to override Myriad’s patentmonopoly on BRCA gene testing.14Politically, both Myriad’s case and

that of provincial and federal govern-ments suffered from miscommunica-tions and misjudgments.15 Federal andprovincial governments debated overwho should solve the gene patentingproblem, ministries could not agree onthe problem or its solution, andprovinces varied in their decisions tocomply with or resist Myriad’s exclusiv-ity claims. Analysts argued that muchof the government response and tacticswere fuelled by nega-tive press againstMyriad’s bullying tac-tics16 and its attempt-ed displacement ofthe public system’spre-existing genetesting program thatincluded patientcounseling.17 Studiesidentifying publicconcern about the potential for genepatenting to limit healthcare accessibil-ity to poorer citizens bolstered govern-ment refusal to bow to corporate intim-idation.18 Thus, government actionagainst single gene patenting may bedriven more by perceived direct threatsto the publicly-owned and operatedhealthcare system than to any govern-ment change toward a broader moralview of the dangers of patenting lifeforms.

Has Anything Changed?At the time of the oncomouse

Supreme Court decision, theBiotechnology Reference Group of theCanadian Council of Churches createda discussion guide of short essays (Life:Patent Pending) that highlights a num-ber of fundamental concerns over thepatentability of whole organisms thatare mentioned above.19 Also men-

tioned is an element of whole organismpatent protection that is often over-looked: patent protection coverage forthe offspring of such whole organismsover the life of the patent. The intro-duction to the discussion guideincludes an appeal to the CanadianParliament to develop laws that direct-ly face the question of whole organismpatentability. Have the Harvard oncomouse deci-

sion and the subsequent landmarkcases resulted in any concrete changesto gene patent law or practice inCanada? After years of intergovern-mental jurisdictional and politicalwrangling, the Patent PolicyDirectorate and Health Canada finallyagreed to consult directly withCanadians through the independentCanadian Biotechnology AdvisoryCommittee (CBAC). Regrettably, near-ly all of its recommendations have beenignored; CBAC was disbanded a few

years ago, its mandate taken up by theScience, Technology, and InnovationCouncil of Industry Canada. Aftermore than seven years the federal gov-ernment continues to simply ignorepatents while provinces are confidentthat they sent a clear signal that com-mercialization of necessary healthcareresources will not work in the Canada.This strategy may have recentlydeterred one recent Canadian licenseeof another patented gene from attempt-ing to enforce its exclusivity rights.Instead, the company has sold kits topublic laboratories.The failure to heed the exhortation to

provide guidance for future investors inCanadian genetic bioresearch throughlegal changes has left the problem incontinued legal as well as moral limbo.Admittedly, the problem is a politicallydifficult challenge to Canadian govern-ments. Any attempt to tighten and

clarify patent laws requires politicalwisdom through a clear picture of themultiple societal values, interests, andrisks. Some analysts have argued forbetter societal and moral guidancethrough a new research framework thatreplaces commercialization with thebroader perspective that considersimplementation of research knowledgeincluding the full breadth of societalimplications.20 Others have proposedan independent governance entity thatwould oversee commercializationthrough patent pools and open sourcestrategies that would facilitate access topatented inventions. Such initiativeswould aim to restore public trustthrough better integration of diversepublic voices and the consideration ofbroader social and ethical issues.21For its part, The Canadian Council of

Churches continues to oppose patent-ing of life forms and commercialexploitation, promotes open exchange

of research ideas forthe common good ofhumankind and thecreated order aroundus, and supports theformal integration ofpublic voices thatconsider the fullimpact of genetictechnologies on thevarious aspects of

societal life in Canada. The Councillauds individual legal decisions that goagainst international currents thatCanadian governments deem sociallyand morally dubious or wrong. But italso continues to urge the establish-ment of proactive legal and moral guid-ance that reflects the diverse moral sen-sitivities of Canadian society and givesdirection to the improved overallhealth of Canadian society. Life isgiven as a gift from God, for us to bothenjoy and to respect.

Members of the Biotechnology ReferenceGroup include: James Rusthoven (chair),Moira McQueen, Stephen Allen, AnneMitchell, Erin Green, RichardCrossman, James E. Read, Paul Fayter,George Tattrie, Mark Boulos, IsaacKawuki Mukasa, Emanuel Kolyvas,Peter Noteboom, and Mary Marrocco.

“Government action against single gene patenting maybe driven more by perceived direct threats to the

publicly-owned and operated healthcare system than to any government change toward a broader

moral view of the dangers of patenting life forms.”

sex. IVF is really intensive, it’s reallyexpensive, and there isn’t even a highsuccess rate. Together with PGD, it cancost something like $18,000; so itmakes sense to assume that peoplewouldn’t want to do that just becausethey want a boy or a girl. But he waswrong, and Jeffrey Steinberg startedoffering this service and got a lot ofpublicity. He also provides IVF for peo-ple who can’t have a baby otherwise,but he says that now 70% of his busi-ness is from people coming to himbecause they want a boy or a girl. There are other fertility clinics that

won’t offer sex selection to just any-body. A lot of clinics will provide it ifit’s for “family balancing.”

Right—the American Society forReproductive Medicine said, “physi-cians should be free to offer pre-con-ception gender selection in clinicalsettings to couples who are seeking‘gender variety’ in their offspring.” Inother words, they approve of sexselection for someone who only haschildren of one gender and wanttheir next child to be the oppositegender. How do you police that?

The main problem with assistedreproduction in the U.S. is that it’s notwell regulated, and even the ASRMguidelines are voluntary.There’s another kind of sex selection

called MicroSort. It’s sperm selection,really: you spin the sperm in a cen-trifuge, and because sperm carryingthe X chromosome are heavier—theyare carrying more genetic material—they separate out from the ones carry-ing Y chromosomes. There have beentrials for that going on for years, and inthat case the clinics are only allowed toadmit a patient who has a child of the

Mara Hvistendahl is a correspon-dent with Science magazine andauthor of Unnatural Selection.

Where did you get the idea for thisbook?

I was researching sex-selective abor-tion in Asia, and mostly unaware ofdevelopments with in vitro fertilization(IVF). But setting up to write this book,I was really determined to find a way tomake it relevant for readers in the U.S.,and I didn’t want them to come awaywith this message that people in Chinaand India are sexist, and that’s whythey abort girls, or that it’s this prob-lem that only happens in other coun-tries. Later, I uncovered this wholeconnection with the population con-trol movement in the U.S. in 1960sAmerica, so there actually was a prettydirect link. Ultimately, I ended up visit-ing fertility clinics in California. I visit-ed The Fertility Institutes and JeffreySteinberg, one of the most notoriouspeople doing pre-implantation sexselection in the U.S.

Is pre-implantation sex selectionhappening very much in the U.S.?

Initially, PGD (pre-implantationgenetic diagnosis) was just used forcouples who had a genetic propensitytoward a disease linked to the sex chro-mosomes. For example, if a woman iscarrying the gene for hemophilia, bysorting for girls, she can guarantee nothaving a child with hemophilia. Mark Hughes, who was very

involved in developing pre-implanta-tion sex selection in the U.S., didn’tthink couples would go through IVFand PGD just to get a child of a certain


opposite sex.But what struck me in writing this

book is that this really isn’t very differ-ent from what parents are doing inAsia. In China and India, they’re typi-cally not aborting female fetuses thefirst time. Most people wait until theyalready have one girl, and then for thesecond child, they go and get an ultra-sound and abort if it’s another girl.

Didn’t India and China both banultrasound testing for the purpose ofsexual selection? Although I don’tknow how well that’s enforced …

It’s not enforced. There have beensome crackdowns, and I actually thinkwhen governments really crackdown itcan be effective, but it’s not reallyenforced.

How do people get around thoselaws?

In China, people told me they bribethe ultrasound technician. In India, theclinics are supposed to register everywoman and to keep track of births,whether each baby was a boy or a girl,but they often don’t have very com-plete records.But you could argue that in a way,

there’s more extensive regulation inAsia than in the U.S. Although PGD isstarting to be introduced in Asia, andthere aren’t strong regulations for that.

What technologies are being usedfor sex selection in other parts of theworld?In most of the developing world, it’s

Unnatural SelectionMore and more parents around the world are gaining theability to choose the sex of their child. Now what?

INTERVIEW WITH MARA HVISTENDAHL

done through an ultrasound scan todetermine the sex, then abortion if it’sa girl. One demographer told me thataccounted for 99% of sex selection inthe developing world.

How does the prevalence of sexselection differ between developedcountries and the developing world?

In most cultures around the world,people want boys, or at least one son.Now the Americans who go in for PGDusually want girls; but generally, thepreference for boys is pretty universal. The situation changes when the fer-

tility rate starts to fall. When you arehaving five or six kids, there’s a goodchance that one of them is going to bea boy. When you’re only having one ortwo kids, you don’t have that guaran-tee. Even in countries that don’t have aone-child policy, people are still havingfewer kids. In India, women are havingonly two kids, maybe one in Delhi. InAlbania the fertility rate is just over onechild per couple. So there’s more pres-sure on women to have a son, some ofit self-imposed.This happens when the fertility rate

drops dramatically in a country—andwhen abortion is legal, or at least avail-able. I connect it to economic develop-ment, because fertility rates tend to godown as countries develop, and at thesame time new technology comes in,

health care improves, and women haveaccess to ultrasound.

How significant is the sex ratioimbalance globally? Are there placeswhere it’s particularly imbalanced?

It’s spreading, actually. It’s significantenough now that the global balance isslightly skewed—it’s now 107 boys per100 girls, when it had been more like105 to 100.Demographers are watching, but it’s

difficult to predict which countries willbe next. Most people didn’t expect it inthe Caucus countries—Azerbaijan,Armenia, Georgia—and now in theBalkans, in Albania, Montenegro,maybe Macedonia.

It’s not hard to see where theimbalance could become a reallyserious problem when everyone isonly having one child, and everyoneis making sure that one child is a son.How serious is the gender imbalancein those countries?

There’s some disagreement, but inAlbania it’s around 110 boys for every100 girls. In Armenia it’s even higher. Itwon’t be around forever in those coun-tries—most demographers believe it’s atransition phase that countries aregoing through as they develop, andeventually they start having moregirls—but it may take several decadesto get to that point.

What is it that changes to makepeople no longer feel that they haveto have a son?

The only place where there was agender imbalance but the birth rate hasnow evened out is South Korea; but thebirth rate has also dropped so low inSouth Korea that people are hardlyhaving any kids. It was the lowest in theworld a few years ago. People I talkedto there didn’t really feel that genderdiscrimination had gone away; it’smore a matter of people not havingmany kids, so it doesn’t really cancelout the decades of sex selection beforeit.In the U.S. the preference for girls is

interesting. Fertility clinics say thatmost couples go in for girls, althoughit’s not hard data, since they don’t haveto report either how many couples aregoing in for sex selection or how manykids are being born through thosemethods. People give all sorts of rea-sons for wanting girls. Some say theywant to raise a strong daughter, thatthey want to raise the first female pres-ident, or that girls do better in schoolnow. There are also some people withmore sexist ideas, wanting to haveprincess parties and that sort of thing.Sex selection, and a lot of these

almost eugenic choices, come upagainst the way that reproductiverights have been framed in the U.S.,which is around this principle ofchoice: that a woman should have theright to choose when to terminate apregnancy. But to some degree that’sbeen extended to include the idea thatshe should be able to choose what kindof child she wants. So there’s a need toreframe that debate around somethingother than “choice.” It just doesn’t workanymore for issues like sex selection.Some bioethicists propose insteadlooking at the right of a child to nothave his or her fate determined beforebirth.

It doesn’t seem like very manygroups are trying to navigate theseissues for fear of confusing theirmessage about abortion rights.

What I found in researching thisbook is that some reproductive rightsorganizations won’t even address thegender imbalance because they don’twant to deal with abortion. As a resultof that, a lot of people in the west don’treally know about it. That’s not theanswer. I think we need to reframe thedebate around something other thanjust “choice.”To me, the right of a child to an open

future makes sense. It’s not that you’recalling for fetal rights, you’re not talk-ing about the embryo as having rights,but the child that is born later shouldhave the right not to have all theseexpectations foisted on him or her.It’s a difficult question, but I don’t

think we benefit at all from steeringclear of difficult questions.



says a representative of NationalGeographic sent to the Hatun Q’eroscommunity, encouraging the commu-nity to come to a presentation whereseven people from NationalGeographic would explain theGenographic Project and seek partici-pants. “Everything is voluntary, there isno obligation,” the letter assures, “butyou are going to have fun and learn alot!” The letter also promises that thepresenters “will use a projector andbeautiful images!”The Hatun Q’eros’ are concerned

with protecting more than their prideand self-identity, though.“The Q’eros, and for that matter

many other indigenous peoples, arefacing outside pressures on their landfrom extractive industries,” Argumedosays. “If the Genographic Project wereto, for example, claim that the Q’eroswere migrants to the Andes from thelowland forests, this information couldbe used by mining interests to bolstertheir argument that they should begranted rights by the Peruvian govern-ment to extract minerals from Q’erosterritory. In fact, although it was notmentioned to the Q’eros, theGenographic Project even says on itswebsite that it wants to study geneticlinks between the Q’eros and lowlandpeoples.”Of course, participants have the

option of simply refusing to give sam-ples. The concern, says University ofCalifornia at Berkeley professorKimberly TallBear, is that potentialparticipants have the opportunity tomake an informed decision. TheGenographic Project addresses this intheir code of ethics, where it affirms

that informed consent in the projectmust be “deliberate, considered, indi-vidual and collective.”The initial letter cited by the Hatun

Q’eros does not appear to meet theProject’s standards. “To the contrary, aone-page flyer with patronizing lan-guage was delivered to the communitynot long prior to the planned DNA col-lection,” TallBear says. “A powerpointpresentation was planned immediatelyprior to DNA collection. This allowsno time for community input to theresearch process, nor for real collectiveconsent as collective discussions takeconsiderably more time than individualdiscussion and consent.”National Geographic spokesperson

Lucie McNeil tells it differently.“Our South American team has been

undertaking outreach and samplingwork with Peruvian leaders, communi-ties and individuals since September2007,” she told GeneWatch. “Ourreception has almost uniformly beenvery positive, and the Peruvians wehave contacted are keen on havingaccess to other ways of learning andadding to their knowledge of their ownhistory. “As for the Q’eros?“We have been reaching out to the

Q’eros communities since 2009,” shesays, and had learned that “verbal per-

The Q’eros, an indigenous commu-nity of the Peruvian Andes, identifythemselves as “the last Incas.” TheQ’eros people fashion their way of life,their traditions, their belief system—their very existence—on their Inca her-itage.How did the community react when

researchers from the NationalGeographic Foundation’s GenographicProject offered to use DNA testing sothat “the people of Q’eros can knowtheir ancestral roots?”As you might expect, there was some

backlash.“The Q’ero Nation knows that its his-

tory, its past, present, and future, is ourInca culture, and we don’t needresearch called genetics to know whowe are,” wrote Benito Machacca Apaza,president of the Hatun Q’eros commu-nity, in a letter asking the regional gov-ernment in Cuzco to prevent theGenographic Project from enteringtheir communities to collect samples.“We are Incas, always have been andalways will be.”“It is disingenuous to presume, as the

Genographic Project has, that indige-nous peoples’ origin narratives and thegenetics narratives will peacefullycoexist in parallel,” says AlejandroArgumedo, Research Director forAsociación ANDES, a Cuzco nonprofitconcerned with protecting the rights ofindigenous peoples. “We believe that the Genographic

Project is blinded by its own ambition.We don’t believe that it came to Cuscowith malice in mind, but its intentionsare wholly self-serving.”Part of the groups’ indignation stems

from a letter which Asociación ANDES

Sacred GroundsA community of “The Last Incas” bristles at NationalGeographic’s attempt to collect their DNA

BY SAMUEL W. ANDERSON


mission of a mayor to come to his com-munity is the necessary step before anysampling takes place.” McNeil stressesthat “only outreach has taken place inthe Q’eros community”—no sampleshave been collected yet—and that “wewere not planning to visit” the QochaMoqo community, which filed thecomplaint. The letter that spurred thecontroversy, ostensibly from a repre-sentative of National Geographic, sug-gests otherwise, specifically addressingthe Qocha Moqo community. NationalGeographic has declined to commenton its knowledge of the letter or itsauthenticity.McNeil says that the Hatun Q’eros at

Qocha Moqo were the only Q’eroscommunity to file a complaint, andthat the mayors of nearby Q’eros com-munities Ch’allmachimpana andChuwa Chuwa had already given theGenographic Project verbal permissionto visit. The Project cancelled their vis-its to those communities after themayor of Qocha Moqo filed his com-plaint. “We received immediate wordfrom the communities ofCh’allmachimpana and Chuwa Chuwathat they are very disappointed that wewere not able to visit them,” McNeilsays. “We have heard they are also dis-appointed with the Mayor of QochaMoqo for filing the complaint on their

behalf - apparently Q’eros protocolrequires him to discuss this with theother communities first.”Both sides say that they have yet to

contact each other directly. In themeantime, McNeil says, “Our SouthAmerican team continues to work suc-cessfully with other communities inPeru. Engagement of around 90Peruvian communities has taken placeand we have 1060 samples.”Don’t expect the Q’eros of Qocha

Moqo to join them.

Samuel W. Anderson is Editor ofGeneWatch.

organ donors—ten years later, Alexis’s“The Farm” still makes a compellingstatement about technology andnature. We are in the midst of our sec-ond generation of genetic modification(the first being the initial domestica-tion of plants and animals), and wehave not yet figured out how to pro-ceed. Alexis draws attention to the fun-damental novelty of genetic engineer-ing in depicting the progression ofdomesticated animals as beginningwith already-domesticated forms, sub-tly omitting their wild ancestors.All of this reminds me of a conversa-

tion that I had with an uncle who is a

farmer in upstate New York. Over abeer in the shade of a barn, we weretalking about how farming haschanged since he was a young man.During the conversation, I excitedlytried to explain to him the possibility ofusing plants with a genetically engi-neered gene involved in stress toler-ance. This gene would be linked to aluminescent beacon, so that when theplants were under drought stress, thebeacon would glow, telling the farmerto water it. My uncle looked at meincredulously and said, “Now howgood of a farmer would I be if I could-n’t tell my crops needed water?”

Rob DeSalle, PhD, is a curator in theAmerican Museum of Natural History'sDivision of Invertebrate Zoology andco-director of its molecular laboratoriesand a member of CRG’s Board ofDirectors.

continued from page 13

GeneWatch Anniversary Archive: 1983-2008

The Council for Responsible Genetics was founded in 1983 to provide commentary and pub-lic interest perspectives on social and ecological developments of biotechnology and medicalgenetics. For a quarter of a century, the Council has continued to publish its magazineGeneWatch with articles by leading scientists, activists, science writers, and public healthadvocates. The collection of GeneWatch articles provides a unique historical lens into themodern history, contested science, ethics and politics of genetic technologies. The full archiveof GeneWatch has been incorporated into this special anniversary DVD that includes an indexof all the authors and titles.

Copies of the anniversary DVD are available for a $100 donation to:Anniversary CRG DVDCouncil for Responsible Genetics5 Upland Rd., Suite 3Cambridge, MA 02140

25 Years of GeneWatch

Greg Lukianoff is a founder and thecurator of the Genetic Music Project, acommunity art endeavor in whichmusicians convert genetic code intosongs. Greg volunteered pieces of hisown code, taken from test results fromconsumer genetic testing company23andMe, uploading them to the web-site for musicians to use as a startingpoint. Although musicians are free toget more creative about the way theyconvert the genome into music, the firstfew songs on the site assign a note toeach of the four nucleotides (A, C, T,and G); pick a FASTA sequence (whichuses those four letters as a shorthandway to express a piece of genetic code)associated with a certain trait (such aslikelihood of baldness or schizophre-nia); and just see what series of notesemerges. When Greg spoke to GeneWatch in

May, the Genetic Music Project hadbeen live for less than two weeks—andhe had already received a song from astranger in Denmark. To learn moreabout the project, listen to the songs,and even upload your own music, visitwww.geneticmusicproject.com.

The process starts when you get agenetic test—yours was from23andMe—and when you get theresults back, you select a chunk ofthe genetic code and assign a note toeach of the four nucleotides. Whatdoes that first piece of code looklike? What does it represent?

The genetic test is selecting theFASTA sequence for certain geneticmarkers [see diagram on facing page].What you’re getting back is, to the bestof my knowledge, the entire FASTA

sequence for an allele. So I put that upthere, and I indicate what conditionsthose alleles are associated with—which provides a lot of opportunitiesfor metaphor and tone for the musicthat people submit.For instance, when I found out that

there was a particular genetic markerfor bitter taste perception, I found theFASTA sequence for it, put that up,and sent it to my friend Amy, who is anunbelievably talented country artist. Ifsomeone was going to sing a song onthe theme of “bitter,” who better than acountry singer?I was really surprised that nobody

had already made a community artproject out of genetic sequencing. Iknew that people had been makingmusic out of genetic code—for exam-ple, the composer Alexandra Pajakwrote an album based on the sequenceof the HIV virus—but given that DNAis part of this wonderful organic sys-tem that grows by its own nature, thatseems to be perfect for a communityart project, something that you just putout into the world and see how it does.Of course, there’s an element of unnat-ural selection to it—I’m curating thewebsite—but at the same time, I don’tknow where it’s going to end up.

You provided the code; who writesthe music?

When the site first went up, prettymuch all of the music came fromfriends of mine who were excited aboutthe idea. Having someone in Denmarkupload a song was something else. Mybig hope is that it continues to grow,and that people recognize that you cango well beyond taking the four individ-ual “notes” from the nucleotides (A, C,

T and G). Using the computational brilliance of

genetics, you can create more andmore complex art. The differentnucleotides could stand for pitch, oryou could even take a bunch ofnucleotide sequences and relate that tothe 64 different settings of a Casio key-board and let the code tell you whichinstruments to use. So there is atremendous amount of fun to be hadwith this, and hopefully it will groworganically.I’m particularly interested in getting

different genres of music, too. I’d reallylove to get a rock song, for example. Ithink when people think of ‘geneticmusic,’ they would first think of somesort of atonal electronica, but as we’vealready shown, it can work out in somany musically interesting ways.

Is there any genre that you thinkwouldn’t work for this project?

I think you could figure out a way tomake any genre work. The only genreI’m not interested in hearing is smoothjazz. Because smooth jazz is terrible.But with real jazz, I actually think

that the surprising twists and turns ofthe FASTA sequences would be perfectfor jazz saxophone. One of the things about the musical-

ity of the genetic code is that it doessurprising things. For example, thepiece on heroin addiction is just basedon the first ten nucleotides of theFASTA sequence for a gene that is sup-posed to indicate that you may be moreeasily addicted to heroin. When sheplayed that, just the first tennucleotides, it was really haunting.Then it can start to get interesting,where you can stumble into themes. It


Musical GenesThe Genetic Music Project encourages musicians to convert DNA code into music

INTERVIEW WITH GREG LUKIANOFF

sounds very traditional, but then it willrun maybe one or two notes longerthan you would expect. You end uphearing some surprising musical thingscome out of it.

Are you coming at this more fromthe science or music side?

I wouldn’t pick one or the other. I’msort of a science hobbyist—it’s thedegree that I never got but alwayswanted to. So I sort of came at it fromthe science side rather than from themusic side. The inherent musicality ofthe information behind all life justseemed irresistible.

Have you learned more aboutmusic or genetics?

I think I’ve learned a lot about both.There were certainly things I didn’tknow about genetics, and there wereplenty of things I didn’t know aboutmusic. That’s one of the things I’m try-ing to be open about, that I’m neither amusician nor a scientist!The difference between this website

and others, really, is that we decided tojust put it out there and see what hap-pens with it, to encourage people to becreative and apply their ownapproach—but also to teach everyone,including me, about the science andthe music behind it.

I noticed that one of the FASTAsequences you posted is supposed tobe the genetic marker for “longevi-ty.” Am I right to figure you’re taking23andMe’s test results with a grainof salt?

One of the things 23andMe does isindicate the amount of research behindthe traits. For some there has been a lotof research and for some there havebeen only tiny studies. They’re good atexplaining it, and this is something Isuspect I’ll eventually be asked; but Itry to make clear that I’m not vouchingfor the accuracy of the information, Ijust think it’s a great starting point.


Top: the FASTAsequence for“longevity,” asdefined by 23andMeMiddle: FlemmingLaugaard, a song-writer in DenmarkBottom: Sheetmusic for “The LongHaul,” written byLaugaard based onthe FASTAsequence above

On April 5th, the MassachusettsLegislature’s Joint Committee on PublicHealth held a hearing to consider therecently introduced “Genetic Bill ofRights” (Senate Bill 1080). At that hear-ing, I testified in favor of the bill alongwith representatives of the ACLU andthe Forum for Genetic Equity. The JointCommittee displayed a strong concernfor the issues presented and indicated arenewed commitment to moving thisimportant piece of legislation forward.Indeed, other states are following theexample. Vermont recently introducedits own “Genetic Bill of Rights” (HR368) and declared April 25, 2011 asGenetic Equity Awareness Day. CRG isworking in partnership with the Forumfor Genetic Equity to advance the“Genetic Bill of Rights” (named afterCRG’s original ”Genetic Bill of Rights”issued in 2000) in other states as well.

Why a “Genetic Bill of Rights”?The Genetic Bill of Rights seeks to

build upon the foundation of therecently enacted federal GeneticInformation Nondiscrimination Act(GINA), an effort I led for fifteen years.GINA was successfully propelled by alegislative campaign that we began inthe early 1990’s to enact state protec-tions against the misuse of geneticinformation in the areas of healthinsurance and employment. As moreand more states began passing suchlaws, the prospects for federal legisla-tion grew and GINA was enacted in2008.Beyond the protections of GINA,

though, there is no comprehensivegenetic privacy law in the U.S. Tenyears after the mapping of the humangenome was completed, the geneticrevolution has led to a tsunami of DNAdata created by genetics research andthe commercialization of suchresearch. And the commercialization ofgenetics is well underway. As more andmore of this personal information

becomes public knowledge, it can bebought and sold by any commercialinterests interested in predictive infor-mation about an individual’s futurehealth status. Current law does nothingto prohibit discrimination in life insur-ance, disability insurance, long-termcare insurance, mortgages, commercialtransactions, or any of the other possi-ble uses of genetic information. Thepublic must be assured that undergoinggenetic testing will not endanger theireconomic security. The campaign to enact a Genetic Bill

of Rights is an attempt to go back tostate legislatures and address this sig-nificant gap in protections for theAmerican public. The bill sets clearlimitations on the use of personalgenetic information in a variety of con-texts unforeseen just a short time agoincluding protections against the use ofgenetic information in workers com-pensation claims and for marketing ordetermining credit worthiness. Withthe proliferation of genetic informa-tion, particularly in consumer contexts,this legislation sets strong standards onthe disclosure of such data and ensuresthat genetic information and materialare treated under state law in a mannersimilar to other medical records andcreates a duty to report in the event ofknown security breaches or unautho-rized use of personal information.Mistakes and other breaches of securi-ty are not uncommon. Just last year, thedirect to consumer genetic testingcompany 23andMe accidentally sentdata of up to 96 individuals to thewrong customers. As genetic research and commercial

genetics applications have proliferated,narrow ethical precepts governinghuman subject’s research have coupledwith little to no regulation of commer-cialized genetics. This toxic combina-tion has ridden roughshod over the rea-sonable expectations and the appropri-ate rights of the people whose data andmaterials are implicated. Take the case

of the Texas Department of StateHealth Services, which sent the geneticinformation of newborns to TexasA&M University for research withoutthe parents consent. Some of thosesamples found themselves in an armedforces database. Or consider the case of members of

the Havasupai tribe, a small, isolatedcommunity who gave DNA samples toresearchers from Arizona StateUniversity to contribute to researchthat could help determine the cause ofthe tribe’s very high rate of diabetes.Nothing much came of the diabetesstudy, but over a decade later, theHavasupai discovered that over 20 aca-demic articles had been publishedbased on studies conducted at the uni-versity using Havasupai DNA, studyingan array of topics the tribe membersnever agreed to. Many membersexpressed their shock at such a betray-al.Such systematic violations of the

expectations of people whose DNA,and personal health information isbeing used without their consent is justwrong. It’s a violation of basic humanrights. Moreover, as commercializationof genetics has exploded, individualsare being the denied the inherent mon-etary value of such information at thesame time that personal genetic infor-mation is becoming widespread and


Massachusetts Legislature HoldsHearing on Genetic Bill of Rights

BY JEREMY GRUBER

our understanding of such databecomes richer and therefore increas-ingly valuable. The Genetic Bill ofRights represents a significant step for-ward in giving individuals back theirautonomy by granting exclusive prop-erty rights to their own genetic infor-mation. Through property rights indi-viduals will gain a series of rightsregarding the control, possession andtransferability of genetic informationthat are unavailable through privacylegislation alone; empowering individ-uals to have initial and on-going control


Endnotes

Paul Root Wolpe, p. 41. Jonsen, AR. (1986) “Bentham in a box: Technology assessmentand health care allocation” Law, Medicine and Health Care14:172–4.

2. Talwar, SK; Shaohua, X; Hawley, ES; Weiss, SA; Moxon, KA;Chapin, JK. “Behavioural neuroscience: Rat navigation guided byremote control.” Nature 417, 37-38.

3. Whitehouse, D. (2002) “Here come the ratbots.” BBC News: May1, 2002 {http://news.bbc.co.uk/2/hi/science/nature/1961798.stm}

Eric Hoffman, p. 61. See “Fishy Business at the FDA,” from Genewatch, Volume 23Issue 4:http://www.councilforresponsiblegenetics.org/genewatch/GeneWatchPage.aspx?pageId=289

2. Twelve of the nation’s largest environmental groups sent an openletter to the FDA asking for an independent and comprehensiveEnvironmental Impact Statement to be completed in place of theless-thorough Environmental Assessment, as mandated by theNational Environmental Policy Act:http://foe.org/sites/default/files/Environmental%20Group%20Letter%20to%20FDA%20-%20GE%20Salmon%20Final.pdf

3. This is an abridgment of DRAFT legislative principles for the reg-ulation of genetically engineered animals developed by the Centerfor Food Safety

Lynn C. Klotz, p. 161. “Continuing Assistance to the National Institutes of Health onPreparation of Additional Risk Analysis for the Boston UniversityNEIDL, Phase 2,” (November 5, 2010) http://www.nap.edu/cata-log.php?record_id=13054

James J. Rusthoven, p. 181. Schwartz, J. and Pollack, A. Judge Invalidates Human GenePatent. New York Times, March, 29, 2010.

2. Pollack, A. U. S. Says Genes Should Not Be Eligible for Patents.New York Times, October 29, 2010.

3. Ray, T. Australian Patient Groups Follow ACLU/PUBPAT Path inChallenging Gene Patenting. GeneWebNews, PharmacogenomicsReporter, June 15, 2010 (http://www.genomeweb.com/dxpgx/aus-tralian-patient-groups-follow-aclupubpat-path-challenging-gene-patenting). Last accessed 7 February 2011.

4. Kesselheim, A. S. and Mello, M. M. Gene Patenting – Is thePendulum Swinging Back? New England Journal of Medicine2010; 362:1855-1858.

5. Harv1.ard College v Canada 2002.

6. Percy Schmeiser and Schmeiser Enterprises v Monsanto Canada andMonsanto Inc 2004.

7. Prudham, S. The Fictions of Autonomous Invention: Accumulationof Dispossession, Commodification, and Life Patents in Canada.Antipode 2007; 39(3): 417, 418.

8. Joly, Y., Caulfield, T., Knoppers, B., and Harmsen, E. TheCommercialization of Genomic Research in Canada. HealthcarePolicy 2010; 6(2): 26.

9. Murdoch, C.J. and Caulfield, T. Commercialization, Patenting andGenomics: Researcher Perspectives. Genome Medicine 2009; 1(2):22.

10. Silverstein, T., Joly, Y., Harmsen, E., and Knoppers, B.M. TheCommercialization of Genomic Academic Research: ConflictingInterests. In: B.M Knoppers and E.R. Gold, eds., Biotechnology,Ethics, and Intellectual Property. Markham, ON: LexisNexis,Canada, 2009, 131-163.

11. Biotechnology Reference Group, Canadian Council of Churches.Life: Patent Pending. A Discussion Guide on Biotechnology and theOncomouse. Available on the Canadian Council of Churches web-site: http://www.councilofchurches.ca/en/Biotechnology/biotech-nology-resources.cfm. Last accessed 8 Feb 2011.

12. The ‘anti-commons’ problem refers to the view that the increasingnumber of private rights over basic biomedical information com-promises biomedical research due to the high transaction cost. SeeHeller, M. A. and Eisenberg, R. S. Can Patents Deter Innovation?The Anticommons in Biomedical Research. Science 1998; 280: 698-701.

13. Gold, E.R. and Carbone, J. Detailed Legal Analysis of GenePatents, Competition and Privacy Law. Appendix B from theWorking Document: Myriad Genetics In the Eye of the PolicyStorm, 2008(http://www.theinnovationpartnership.org/data/ieg/documents/cases/TIP_Myriad_Legal.pdf). Last accessed 7 February 2011.

14. Gold, E.R. and Carbone, J. Myriad Genetics: In the Eye of thePolicy Storm. Genetics in Medicine 2010; 12(4): S53.

15. Ibid, S52.16. Caulfield, T., Bubela, T., and Murdoch, C.J. Myriad and the MassMedia: The Covering of a Gene Patent Controversy. Genetics inMedicine 2007;9(12): 850-855.

17. Gold and Carbone 2010, S50.18. Caulfield, T., Einsiedel, E., Merz, J.F., and Nicol, D. Trust, Patents,and Public Perceptions: The Governance of ControversialBiotechnology Research. Nature Biotechnology 2006;24(11): 1352-1354.

19. Biotechnology Reference Group, Canadian Council of Churches.Life: Patent Pending.

20. Gold and Carbone 2010, S54.21. Joly 2010, 30, 31.

over the use of their own genetic infor-mation. In turn, providing individualswith greater control over the use oftheir genetic information will, morepractically, encourage otherwise reluc-tant individuals to participate inresearch by balancing their interestswith the interests of those who seek touse such information for a variety ofpurposes.For these reasons, we are working

hard with our organizational partnersto pass strong and comprehensive lawsproviding property and privacy rights

for genetic information and geneticmaterial. The Genetic Bill of Rights, ifenacted, would confer upon Americansa significantly expanded set of rightsthan exist under current law and placethe United States once again in itsrightful role as a leader in addressingthe social and ethical implications ofnew technologies and biotechnologiesin particular.

Jeremy Gruber, JD, is President andExecutive Director of the Council forResponsible Genetics.

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GeneWatch Vol. 24 No. 2