GeneWatch Vol. 24 No. 2

Volume 24 Number 2 | April-mAy 2011

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

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

- Paul Root Wolpe, page 4

ISSN 0740›9737

PLUS: > National Geographic draws the ire of “the Last Incas” > Making music with your genome > Exclusive interview: Mara Hvistendahl, Unnatural Selection

GENEWATCH april-May 2011 VoluMe 24 NuMber 2 eDiTor & DeSiGNer Samuel W. Anderson eDiToriAl CommiTTee

ruth Hubbard Sheldon Krimsky Jeremy Gruber GEnEWatch is published by the Council for responsible Genetics (CrG), a national, nonprofit, tax-exempt organization. Founded in 1983, CrG’s mission is to foster public debate on the social, ethical, and environmental implications of new genetic technologies. The views expressed herein do not necessarily represent the views of the staff or the CrG board of Directors.

address 5 upland road, Suite 3 Cambridge, mA 02140 phoNe 617.868.0870 fax 617.491.5344 Net www.councilforresponsiblegenetics.org board of directors SHelDoN KrimSKy, phD, Board chair Tufts university peTer SHoreTT, mpp treasurer The Chartis Group eVAN bAlAbAN, phD mcGill university pAul billiNGS, mD, phD, university of California, berkeley SuJATHA byrAVAN, phD Centre for Development Finance, india roberT DeSAlle, phD American museum of Natural History roberT GreeN, mD, mpH boston university Jeremy Gruber, JD Council for responsible Genetics rAyNA rApp, phD New york university pATriCiA WilliAmS, JD Columbia university staff Jeremy Gruber, President and Executive Director Sheila Sinclair, Manager of Operations Samuel Anderson, Editor of GeneWatch Andrew Thibedeau, Senior Fellow magdalina Gugucheva, Fellow CoVer ArT Samuel W. Anderson eDiToriAl & CreATiVe ASSiSTANT Grace Twesigye unless otherwise noted, all material in this publication is protected by copyright by the Council for responsible Genetics. All rights reserved. GeneWatch 24,2 0740-973

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Editor’s Note Some opponents of various biotechnologies—particularly genetically modified foods—have a tendency, even when they could be citing scientific and economic studies that back their position, to fall back on the “yuck factor.”

Illustrations of snarling anthropomorphic cornstalks tend to grab one’s attention faster than carefully written arguments in a magazine. It may work, but vague queasiness and discomfort with the unfamiliar are hardly the recipe for an educated opinion.

In discussions about bioengineered animals, the yuck factor is alive and well. (Pigs that glow in the dark? Gross!)

So too, however, is its counterpart, one less common in discourse on GM crops: the “cool factor.” As Paul Root Wolpe points out (on page 4), it’s easier to latch onto an individual case, and a number of individual animals have gained fame—or infamy—for their bioengineering, with nicknames to boot.

Our cast of characters includes: Dolly: The first cloned sheep.

The Beltsville pigs: Seventeen pigs developed to express extra growth hormones, but suffered an array of ailments as a result and became an icon for animal welfare activists.

The Vacanti Mouse: Lab mouse with what looked like a human ear (actually shaped cow cartilage) on its back.

ANDi: Lab monkey genetically altered with a jellyfish gene, to make it glow.

Enviropig: Developed to have reduced phosphorous levels in its manure.

Popeye pigs: Purportedly healthier pigs as a result of an introduced spinach gene which lowered levels of saturated fat.

By SaMuElW.anDErSOn Whatever the researchers’ intentions, the projects that make the news are often those which can most easily be framed in an attention-grabbing way. The New Scientist dubs bioengineered animals “creatures with bonus features,” and various websites and blogs have posted their lists of the “top ten coolest” or “most bizarre genetically modified animals.” In some bioengineered animals, pets in particular, “coolness” is actually their primary utility. GloFish (the name is selfexplanatory) are marketed specifically as pets, were granted approval for sale in the U.S., and have already spawned imitators—although their original intended use was as a warning system for pollution levels in water.

It’s easy to get distracted by the bizarre bioengineered animals, but the majority of the most important ones don’t glow under a UV light. “Knockout mice,” engineered not to express a certain gene, are a lab standby and could lead to “knockout monkeys.”

Genetically modified salmon look just like regular salmon, only larger, but they pose very real risks to natural fisheries and ocean ecosystems. Pigs modified to be human organ donors are certainly bizarre in concept, but on the outside they still look like pigs.

Bioengineered animals are a strange lot, to be sure; but within that lot, as far as the impact a modified animal may have on the human and natural world, the book can rarely be judged by its cover.

Write (for) GeneWatch GeneWatch welcomes article submissions, comments and letters to the editor. Please email anderson@gene-watch.org if you would like to submit a letter or with any other comments or queries, including proposals for article submissions.

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Ethical Limits to Bioengineering Animals

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

PAUL ROOT WOLPE

Food and Drug Amalgamation

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

Food Unchained Researchers are having a difficult time genetically engineering livestock to produce food better than their non-engineered counterparts SAMUEL W. ANDERSON

Goat Pharming

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11

An interview with William Ravis, chief veterinarian at GTC Biotherapeutics CRG STAFF

Back on “The Farm”

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The story behind an iconic painting and its vision of the future, a decade later ROB DESALLE Topic update: Federal Circuit Hears Appeal in Myriad Gene Patent Case

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SARS in the City

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

LYNN C. KLOTZ

Gene Patenting in Canada

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From the OncoMouse to cancer gene testing and beyond JAMES J. RUSTHOVEN

Unnatural Selection

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More and more parents are gaining the ability to choose the sex of their child ... now what?

INTERVIEW WITH MARA HVISTENDAHL

Sacred Grounds

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A community of “The Last Incas” bristles at National Geographic’s attempt to collect their DNA SAMUEL W. ANDERSON

Musical Genes

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The Genetic Music Project encourages musicians to convert DNA code into music INTERVIEW WITH GREG LUKIANOFF

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Topic update: Massachusetts Legislature Holds Hearing on Genetic Bill of Rights

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Endnotes

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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 The history of humanity’s use of animals for its own purposes is not a particularly benevolent one. We have used animal flesh for our meals and fur for warmth, bones for weapons and skin for parchment, blubber for oil and horns for medicine. We have harnessed their bodies for labor and domesticated them as companions. We have killed them for sport, worked them to death, and used them for experiments without anesthesia.

Today, we believe we are better. We have laws against animal cruelty and strong public sanctions for mistreatment of animals. At the same time, though, we have transformed individualized exploitation of animals into industrial animal processing. Each year, billions of chickens and millions of turkeys have their beaks partially cut off so that they can be crowded into warehouse-sized barns without cannibalizing each other. Cattle are fed unnatural diets and sometimes castrated without anesthesia, while geese are force-fed to fatten them up for pâté.

Of course, one could go on. No need here to review the litany of our current cruelties or to lament our lack of concern for the suffering of the animals we consume; there is a vast literature on those things and their ethical implications (from Peter Singer’s Animal Liberation [1975] to Jonathan Safran Foer’s Eating Animals [2009]). Yet, despite our general inattention to the quality of life of our livestock and poultry, we still maintain that, as a society, we care about the treatment of animals. We are outraged when a famous quarterback is caught with fighting dogs, we give money to save endangered species, we individually wash oil-

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soaked birds in the gulf.

We are deeply conflicted about our treatment of animals as a society; so when we see the use of animal bodies as platforms for genetic experiments, it is little wonder that we are confused about how to react.

Our conflicted attitude toward animals expresses itself in many ways. I often present the idea of using transgenic pigs to provide heart valves and whole heart transplants to my undergraduate students as provocatively as possible, by saying: “Imagine! You can create a drove of transgenic pigs whose hearts are not as immunoreactive to humans, or, perhaps, even engineer a pig to grow a heart using some genes

bacon for breakfast react so strongly to the idea of slaughtering a pig for its heart? After all, no one is going to die without bacon, and we are sacrificing the transgenic animal to save a person’s life.

The answer lies in our tendency to personalize morality. We are far more likely to feel a responsibility to one person who is suffering than to groups who are suffering. Charities raising money for poverty in developing nations know it is far more effective to tell one person’s story than to cite statistics. It is also manifested in what Albert Jonsen referred to as the “rule of rescue.”1 If you ask people whether insurance companies have a right not

Why is it that students who had bacon for breakfast react so strongly to the idea of slaughtering a pig for its heart? from the intended recipient. Then, when the heart is needed, you can choose the best pig, slaughter it— maybe right in the hospital—and transplant the heart directly into the human being!”

The reaction is immediate and passionate, and predictable. Students object that keeping pigs at the ready to be slaughtered for hearts is wrong.

“Why?” I ask. The best response I usually get from students (or at least, those who have taken Intro to Philosophy) is that it is using the animal entirely as a means, and that is wrong. My next question, of course, is whether they eat meat.

Why is it that students who had

to reimburse experimental, unproven treatments, a majority say yes.

However, if you then give them a particular case of a particular person—a woman with treatment-resistant breast cancer, for example—the same people think it unconscionable that the insurance company will not pay for any and all experimental treatments, even those with only a remote chance of helping her. Personalize the case and our general principles often go out the window.

Students feel sorry for that particular chicken, or pig, but not so much for chickens and pigs in general. The thought of slaughtering “pigs” for bacon seems not to offend some viscer-

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al sense of fairness, while slaughtering that particular pig to put its heart in that particular person seems to create an ethical calculus that we do not put into play with masses of animals. One death a tragedy, a million deaths a statistic.

The same reaction seems to be operative in our response to laboratory animals. The same mice we can glue-trap or snap-trap in our basements must be euthanized consistent with the recommendations of the American Veterinary Medical Association Panel on Euthanasia when killed in a lab.

Vermin in the home turn to protected subjects in the lab.

The reactions to biotechnologically engineered animals, then, become complicated. Is there anything really wrong with using green fluorescent protein to create a glowing rabbit, fish, or monkey?

Should we protest the construction of an ear-shaped polymer scaffolding on the back of a mouse? Do we cross a line when we create flocks of transgenic animals as bioreactors, or to be ‘pharmed’ for drug molecules? Is it ethically questionable to wire electrodes into animal brains to control behavior, or to keep disembodied animal brains alive in nutrient media?

With all the suffering that we bring to animals caught up in agribusiness, is it not better to create an animal that is well taken care of, even if it has been engineered with genes that make it glow or express a protein in its milk?

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

The conflict becomes clear in cases such as the experiments of Sanjiv Talwar and John Chapin and their colleagues at SUNY, who wired rats with electrodes in their sensorimotor cortex and again in their pleasure centers (medial forebrain bundle), and then controlled the rats movements by stimulating them to turn right or left as the

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experimenter desired.2 Animal rights groups and ethicists often complained that these animals were denied their autonomy, turned into “ratbots” or “roborats.” Even Sanjiv Talwar admitted that the “idea is sort of creepy.”3 Yet we use animals for work and recreation purposes every day in ways that significantly restrains their autonomy, whether they are drug-sniffing dogs or plow oxen or aquarium dolphins or canaries in a cage. Are roborats really any worse off?

Clearly, from an ethical perspective, the suffering of animals in general does not free us from the obligation to treat our animals ethically in the laboratory or biotech industries. So what is wrong

with the roborat?

The difference between robo-rats and drug-sniffing dogs, for example, is that in the case of the dogs, they are trained to exhibit certain behaviors, then rewarded with affection or food for those actions. They are taught to understand, and are rewarded for understanding. Dogs unable or unwilling to conform are not used as work dogs. The robo-rats, on the other hands, do not really understand what they are asked to do, and the rewards, delivered directly to the brain, do not conform to the nature of rewards we generally expect to give animals—food, for example—which connect an understandable action to a primary biological function, in the hands of a recognizable human master. The robo-rat does not understand the behavior being asked and does not participate in

the reward being offered, and it has no potential relationship to the master. All is done remotely, both request and reward, through impulses sent directly to the brain. In that sense, the robo-rat is instrumentalized beyond the pet or work animal, and is denied a level of autonomy given even to farm animals and caged pets. The violation in the case of the robo-rat is taking that last step: removing all relationship with the animal and truly treating it as a mechanism to be controlled rather than a living creature.

The lines are not clear, and the standards shift with time and place. As we begin to create animals whose very bodies are pharmaceutical manufacturing plants, whose organs provide life-saving transplants, and whose bodies have altered genetics and physiology to provide experimental platforms for our science, we have to scrutinize our motives and our actions.

Animals are both commodities and autonomous beings, and in order to maintain our rights to consider them as the former, we are obligated at the same time to honor the latter. Clearly, there is a certain amount of self-contradiction involved. We do not treat all animals the same, and we have different standards even for the same animal in different contexts. Our pretenses, however, do not absolve us of our ethical responsibilities. As we create new ways to integrate biotechnologies into animal bodies, we must constantly revisit and redefine the line between the use of animals and their exploitation, the control of behavior and their right to a certain level of autonomy, and the instrumental use of animals for the general welfare and the manipulation of animals for our curiosity or entertainment. There may be no better measure of our humanity than how we treat our animals.

Paul Root Wolpe, PhD, is Professor of Bioethics and Director of the Center for Ethics at Emory University.

GeNeWatch 5

Food and Drug Amalgamation The FDA is readying to approve genetically engineered salmon ... as a “drug”

BY ERIC HOFFMAN

The environmental dangers posed by the FDA’s approval of genetically engineered salmon for human consumption were highlighted in the fall issue of GeneWatch.1 Unfortunately, a whole herd of genetically engineered animals are in the works. If we do not fix our inadequate regulatory system now, we could face a host of irreversible risks in the future.

In the U.S., the process of regulating biotechnology comes from the “Coordinated Framework for Regulation of Biotechnology,” which was created in 1986 to prevent biotechnology-specific regulations from being written. In their place, agencies were asked to use current rules and find ways to apply them to biotechnology products. The coordinated framework also designates which U.S. agencies will oversee which products. For example, the USDA approves genetically engineered (GE) crops before they can be planted, while the FDA governs GE crops once they leave the farm. The FDA also regulates GE animals for the production of food and pharmaceuticals. This has led to 6 GeNeWatch

an absurd status quo, with FDA approving GE animals not as new foods, but as new animal drugs.

The FDA defines a “drug” as something that is intended to affect an animal’s structure or function. For GE animals, recombinant DNA (the engineered genes) qualifies as a “drug” under the FDA’s definition. It is important to note that in the case of GE salmon, this “drug” does not improve the health of the salmon or the people consuming it. In fact, the rDNA construct that produces growth hormone year round is responsible for a number of adverse effects, such as jaw erosion and other physical abnormalities in the salmon, the potential for increased allergenicity among human consumers, and lower ratios of Omega-3 and -6 fatty acids in the meat—even though the presence of these healthy fats is one of the primary reasons many people choose to eat salmon in the first place.

The only reason GE salmon is being proposed as a “drug” is to allow the company that produces it to avoid the more stringent regulations that it may

be subjected to if the GE salmon were defined as “food.” Yet the salmon’s recombinant DNA makes for a poor drug, as - it does not appear to provide any benefit to consumers or the environment. Like trying to fit a square peg into a round hole, the FDA is trying to force a genetically engineered food product into a regulation written for drugs.

Using the New Animal Drug (NAD) process to approve GE animals is also inappropriate, as it only compares the risk of GE salmon compared to eating non-GE salmon. The process fails to properly look at the major impact GE salmon will have on the environment or human health. It does not look at the impact GE salmon farming will have on fishing communities or the impact expanding use of GE salmon will have on the production and consumption of these fish. The NAD process does not require a proper costbenefit analysis, nor does it look at alternatives to using GE fish entirely.

At the heart of the issue, the NAD process fails to look at GE salmon approved for food as food and slyly april-May 2011

tries to get these fish onto our plates without the proper precautions or environmental review.

While this “frankenfish” is unsettling to most Americans (91% of whom don’t want this fish to reach their plates), the trouble with GE animals does not end there. The same company that is marketing this GE salmon, AquaBounty Technologies, also has GE tilapia and GE trout waiting in the pipeline for approval. Another company, Hematech, is working on GE cows that theoretically cannot get mad cow disease, which begs the question: Is it really easier to alter the genome of a cow to stop producing prions in its brain than to simply stop feeding cows dead animal brains (which is how mad cow disease is spread)?

Other companies are looking into

& Drug Administration’s Veterinary Medicine Advisory Committee held a public hearing on the approval of GE salmon last September. Since then, the FDA has remained silent on the issue as it finalizes its Environmental Assessment, which will be posted for a 30-day comment period sometime soon (and will likely be completely inadequate).2 Approval will shortly follow this Environmental Assessment if the FDA does not find any significant environmental harms.

Since the FDA’s hearings on the GE salmon, two federal bills were introduced in both the House and Senate by Senators Mark Begich (D-Alaska) and Lisa Murkowski (R-Alaska) as well as Representative Don Young (R-Alaska).

These bills would ban the approval of GE salmon or require labeling if the

“If the FDA approves the GE salmon for human consumption, it will open up a floodgate of GE animals onto our plates—and it is likely GE food products will not even be labeled as such.” developing GE chickens that are unable to transmit bird flu, and recent reports from China revealed that researchers have created a GE cow that makes “human breast milk” instead of cow milk. And of course there is the “Enviropig” from a Canadian university, a transgenic pig that produces less phosphorus in its waste—allowing industrial animal factories to shove even more pigs into their tightly confined feedlots while continuing to pollute as much as they do today.

If the FDA approves the GE salmon for human consumption, it will open up a floodgate of GE animals onto our plates—and it is likely GE food products will not even be labeled as such.

These approvals will all happen under the illogical regulatory framework of approving GE animals for food as “animal drugs” and not the foods they truly are.

So where are we now? The U.S. Food

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fish is indeed approved. The current legislation proposed in Congress is important but the bills, if passed, are only a temporary fix for the larger problem of a completely inadequate system surrounding GE animal regulation.

What would the proper oversight of GE animals look like? Below is an outline of what regulations on GE animals that protect human health and the environment would entail.

Legislation on the approval, use, and commercialization of genetically engineered animals must: 1. Encompass all GE organisms for human or animal food, or food and feed containing GE organisms.

2. Require independent and comprehensive risk assessment of GE organisms, including: - Analysis of the engineered genes and their long term stability over multiple generations;

- Safety of eating the GE animal or products from the GE animal; - Comprehensive and independent environmental impact reviews, including whether approval of any animal with a wild relative that lives in or could 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 the animals.

3. Require labeling of GE animals for: - All products intended for human or animal consumption that have been genetically engineered; - Any foods containing any amount of GE product; and - The creation of a tracking system of GE animals and products through the food supply.

4. Mandate transparency in the approval process with adequate time and ability for public participation.3 Until such regulations are put in place, all decisions on the approval of GE animals for food must be stopped.

Our current way of regulating GE animals as “new animal drugs” is nonsensical and does not require the proper analysis of risks to human health, the environment, the health of wild-type populations related to the GE animals, the economic impact these GE animals may have, or the level of transparency needed to guarantee a reasonable level of public participation in the decisionmaking process.

Contact your members of Congress today and ask them to co-sponsor HR 520 and HR 521 (in the House of Representatives) and S 229 and S 230 (in the Senate) to stop the approval of GE salmon or require that these fish be labeled if approved.

Eric Hoffman is Biotechnology Policy Campaigner at Friends of the Earth U.S.

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Food Unchained Researchers are having a difficult time genetically engineering livestock to produce food better than their non-engineered counterparts

BY SAMUEL W. ANDERSON Over 10,000 years ago, humans began to domesticate animals.

Livestock—sheep, goats, and cattle in Southwest Asia, pigs in current-day China—began to replace hunting as the primary source for meat and skins.

Humans found new uses for animals: collecting milk from lactating ruminants and eggs from poultry; harnessing cattle, donkeys, and water buffalo to plows; shearing the wool from sheep and alpacas; climbing onto the backs of horses and camels for personal transportation; and, of course, producing biopharmaceuticals using proteins extracted from the milk of transgenic goats.

If that last item sounds a bit abrupt in the chronology of animal domestication, that’s because it is. Even after thousands of years of selective breeding, farmers and animal science researchers in the 20th century found plenty to improve upon. The establishment of new and enhanced livestock breeds moved at an astonishingly rapid pace, as developments that might have taken centuries were accomplished in decades. Yet, while modern farmers and researchers possessed tools unavailable to their forbears, they still relied on selective breeding to achieve genetic upgrades.

In the 1980s, the advent of recombinant DNA technology appeared to herald a new age in animal agriculture, allowing the engineering of specific genes and selective introduction of novel traits. Scientists began creating transgenic animals that served as better lab subjects, (such as “knockout mice,” engineered not to express a certain gene); enhanced animal-generated 8 GeNeWatch

biotherapeutics (such as pharmaceutical proteins from sheep’s milk, first at Roslin Institute in 1989); could potentially develop into future organ donors (usually attempts at pigs modified to grow specific organs compatible for transplant into humans); and even novelty pets (starting with the fluorescent GloFish).

This period also marks when researchers began attempting to apply germ-line engineering to improve animals’ food production. Unlike other types of transgenic technologies, most of which aim to adapt animals for novel uses, attempts to upgrade livestock-based food production through transgenics pits genetic engineering against the time-tested mechanisms of selective breeding that had gradually honed those same characteristics over millennia. Humans have been developing specialized varieties of sheep for at least six to eight thousand years, selecting for some of the same traits— fast growth rates, feed conversion efficiency—that the Roslin Institute has tried, mostly in vain, to improve through genetic engineering.

Meanwhile, when other researchers at Roslin began engineering transgenic sheep that produce biotherapeutic proteins in their milk, they were attempting something that couldn’t be done through conventional methods.

And unlike bioengineered food animals, “pharming” reached the market and is being adopted in new forms.

GTC Biotherapeutics (see page 11) was the first to get regulatory approval for a pharmaceutical produced by a transgenic animal with ATryn, an antithrombrin derived from the milk

of transgenic goats. Other companies have since developed goats, cows, and even rabbits that can produce various therapeutic proteins in their milk. The end product may not be novel, but the means certainly is. Most of the biotherapeutics being produced through animal pharming are already commercially available through other production means, but the strength of pharming is its potential to manufacture the same product at a significantly lower cost. A few hundred of GTC’s goats can produce as much antithrombrin proteins as a lab that costs millions of dollars to set up and millions more to scale up.

The same cannot always be said of transgenic food animals. In many cases, germ-line engineering of a foodproducing animal may be used to attempt to extend the aims of conventional breeding; in other words, to improve food production. These traits can be improved without genetic engineering, of course, and have been for thousands of years, but genetic interventions can produce much more drastic results—for better or worse.

AquaBounty’s genetically modified salmon grows far more rapidly than its conventional counterpart, and although this “improvement” raises a host of serious concerns (detailed by Eric Hoffman on page 6), from a strictly production-oriented standpoint, it could be a boon to some fish farmers (and certainly to AquaBounty). On the other hand, when the United States Department of Agriculture funded the development in the 1980s of pigs carrying the human growth hormone in an attempt to create a faster growing, april-May 2011

leaner meat animal, the results yielded only a sickly litter afflicted with an array of odd conditions, including pneumonia, peptic ulcers, and arthritis.

Of the 19 now-infamous “Beltsville pigs,” 17 died before reaching one year of age.

These ventures may have resulted in an animal welfare fiasco and the very real threat of a catastrophic disruption of ocean ecosystems, but we can at least see why they were carried out.

The achievement—or intent, in the Beltsville pigs’ case—was to more efficiently convert grain to meat, doing so with one radical improvement that may have taken many years to accomplish through conventional breeding.

Many other endeavors to improve livestock food production through germline engineering appear redundant or superfluous, which may explain their tendency to either fail or fizzle out. Ironically, many of these projects also receive the most press, if only for their novelty:

acid.

- In the 1990s, British researchers began attempts to develop transgenic sheep resistant to scrapie, a prion disease similar to bovine spongiform encephalitis (or mad cow disease), which is 100% fatal in sheep. Research has also been undertaken to develop cows resistant to mad cow disease, so far with no published success.

The prevailing flaw in these tech-

- “Enviropig,” developed by A “Beltsville Pig” researchers at Ontario’s University of Guelph, is able to nologies—presuming they were sucdigest a form of phosphorous in feed cessfully developed—is that while the grains that it would normally method may be novel, the result is not. excrete, reducing the phosphorous A surprising amount of research on levels of its manure by 30 to 70%, transgenic food animals has been bent with the aim of diminishing the envion achieving what can already be ronmental impact of large-scale hog accomplished more gracefully through production. conventional breeding, altered pro- Akira Iritani, a scientist at Japan’s duction practices, or human behavKinki University, reported in 2002 ioral adjustments. In many cases, all of that his team was the first to suc- the time and money spent developing cessfully add a functioning plant a new transgenic livestock breed gene to an animal, in the form of pigs serves only to replace an existing soluthat carried a spinach gene. As a tion, even if it is more efficient, effecresult, Iritani said, the pigs’ carcass tive, and sustainable than a genetically held 20% less saturated fat, convert- engineered silver bullet. ed by the novel gene into linoleic Take the above examples:

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- “Enviropig” is awaiting approval for human consumption in Canada and the U.S., and already has the green light from Canada’s Department of the Environment and the blessing of swine industry groups. Yet, it represents an incomplete solution (phosphorous is not the only problem nutrient in pig manure) to a problem that already has solutions at hand.

Unfortunately, those alternatives— changing the pigs’ rations by adding an enzyme (phytase, which can reduce phosphorous in manure by over 50%) or using different grains; being more careful and strategic when spreading manure on fields as fertilizer; and most of all, ditching the vast 10,000+ hog confinement operations in favor of smaller, diversified farms—require behavioral changes in the hog industry, as opposed to maintaining the status quo with new pigs.

Enviropig has been framed by its creators and the swine industry as an environmental breakthrough, but from the perspective of environmental protection, it addresses a problem that already had known solutions. In reality, despite the name, Enviropig was designed to solve hog industry problems. It reduces the amount that producers need to spend on mineral supplements, but more importantly, it allows the hog industry to appease regulators and scale up operations without changing the prevailing practices.

- Iritani’s “Popeye pig,” with apparently 20% of its saturated fat converted to healthier unsaturated fats by an inserted spinach gene, never resurfaced after it was announced in 2002. At the time, Iritani essentially admitted that he did not expect the GeNeWatch 9

pig to be commercialized due to lack of public acceptance; but he also expressed his hope that “safety tests will be conducted to make people feel like eating the pork for the sake of their health.” The notion of encouraging people to eat pork for their health may raise an eyebrow; beyond that, one need not think too hard to come up with simpler ways to cut down on saturated fat (trim it off of your pork chop, or simpler yet, cut back on the meat).

- Attempts to engineer transgenic scrapie-resistant sheep appear to have fallen by the wayside, presumably because many sheep already carry a dominant gene for scrapie resistance, allowing producers, after sending biopsies to a lab, to select against scrapie susceptibility.

Mandatory scrapie ID tags in the U.S. and other countries have also helped track and control the spread of scrapie. The best argument that conventional breeding and well-executed containment practices preempt any usefulness of transgenic scrapie-resistant sheep is their success: Australia and New Zealand have 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’ genomes to grant them mad cow resistance is essentially a superfluous advance.

While some research suggests that genes can influence mad cow resistance or susceptibility, the disease is most often believed to be contracted when brain tissue from another animal mad cow disease carrier (or scrapie, some studies say) enters into a cow’s feed. In the U.S. and Canada, stringent steps to keep ruminant tissue out of ruminant feeds helped essentially eradicate mad cow in North America—no transgenic influence needed.

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Despite the headlines about cows that produce something akin to human breast milk or cattle genetically engineered for immunity to sleeping sickness, the most marked shortcoming of transgenesis as a means of improving food animals is evidenced by the host of experiments that don’t make headlines. Attempts to create healthy, fast-growing transgenic sheep carrying the human growth hormone began in the mid 1980s. In early experiments, the transgenic lambs grew at average rate until reaching 15 to 17 weeks, at which point “over expression” of the growth hormone resulted in two rather counterproductive side effects: “reduced growth rate and shortened life span.” Fifteen years later, growth hormone experiments in sheep had only managed to yield larger than normal sheep. At 12 months, transgenic rams were only 8% larger than the control rams, and with no significantly increased feed efficiencies noted.

AquaBounty’s success bringing genetically modified salmon to market is, so far, an anomaly; to date, no other animal has been commercialized carrying a transgene that increases the amount of food it produces or the effi-

ciency with which it converts feed to meat, milk, or eggs. Meanwhile, the goats, cows, chickens, and even rabbits that have been developed to produce human biopharmaceuticals are, in some cases, already proving to be the most economical producers of some therapeutic proteins. Pharming is not without its drawbacks, and the need to carefully test and regulate all products of transgenic animals is evident.

Nonetheless, if a genetically modified animal is to deliver significant benefits for humans, there certainly seems to be a surer path for those using genetic engineering to coax an entirely new use out of an animal which has been selected on the basis of its existing advantageous traits; as opposed to those projects taking on conventional breeding programs at their own game—attempting, with a single transgenic silver bullet, to outshine thousands of years of purposeful selection.

Samuel W. Anderson is Editor of GeneWatch.

april-May 2011

Goat Pharming An interview with William Ravis, chief veterinarian at GTC Biotherapeutics

BY CRG STAFF to efficiently use animals within our operation.

GTC Biotherapeutics was the first company to bring a pharmaceutical product to market which had been derived from transgenic animals, using goats modified to produce therapeutic proteins in their milk. The product, ATryn (an antithrombrin) received regulatory approval in the EU in 2006 and in the U.S. in 2008. Dr. William Ravis, DVM, is the chief veterinarian at the company’s Massachusetts farm.

How many goats does GTC currently have on the farm? Do you think of it more as a “farm” or a “lab”?

While our facility in Charlton is indeed a farm, it is a very unique and specialized facility licensed by the appropriate regulatory agencies to house the goats and to produce human recombinant therapeutic proteins in their milk. Currently, we have approximately 600 goats on the farm.

After inserting the transgene into early stage embryos, what are your success rates getting live births and offspring that carry the transgene?

What happens to the offspring that don’t carry the transgene?

We use more than one technology to insert the transgene of interest, and while we do not disclose our success rates for those programs, we do feel we have developed a certain expertise in this area and have a (comparatively) high level of success.

With regard to offspring that do not carry the transgene, there are other potential uses for those animals within our operations (such as use in breeding in future programs). We work very hard

How do you respond to concerns about animal welfare in using goats to produce biotherapeutics rather than, say, bacteria?

We do not believe that there are any animal welfare concerns inherent in the use of goats for producing milk that contains a human recombinant therapeutic. On the contrary, the goats at GTC are very well cared for and enjoy some benefits not found on a traditional dairy farm, such as full-time veterinarian oversight and regular health checks.

The bottom line is that we are maintaining and milking dairy goats in a very similar fashion to how it is done in the commercial goat milk industry – albeit with significantly more monitoring and documentation. The only difference is that our animals have an additional piece of DNA that affords them a unique ability to produce an additional specific recombinant protein in their normal milk production.

With regard to comparisons to the bacterial fermentation platform for biologics (or other production systems for recombinant therapeutics), we at GTC feel that our system has a number of significant advantages in comparison. Not only can we produce a number of molecules that bacterial fermentation cannot, we can also produce therapeutic proteins in a very cost effective fashion. As you are aware, the state of our health care system begs for a capability to produce medicines that will start to bring down the cost of life saving therapies. Lastly, there are at times significant limits to alternative production systems that impact the availability of these medicines and therefore limit their usefulness to the general popula-

tion that might need them. Our system of production has clearly shown a significant ability to produce large quantities of these medicines that could meet the current unmet medical needs for more patients Do you see transgenic dairy goats as the ideal production method for drugs like ATryn? Is there a “next step” from here, or is it just a matter of tweaking the system you already have in place?

In the case of antithrombin/ATryn, yes, we believe that the product is best suited for the goat. Our next steps from here are always looking for improved efficiencies across the whole process but we will be staying with the goats as the production species. Additionally, we will be exploring unmet needs for this product through the development of new indications that have not been previously explored, possibly due to limited supply or perhaps over safety concerns of the risks of blood-borne pathogens, for the competing plasmaderived alternative that is currently on the market.

As you develop your breeding herd, what qualities do you select for to mold the perfect human-protein producers?

The attributes that we look for are what you might look for in any commercial dairy operation across the country. We look for those goats that pass on superior dairy genetics with regard to daily volume of milk production as well as overall length of lactation. Additionally, all dairy animals have slight variability that impact the proteins found in their milk, so we also select for goats with optimal protein production. continued on page 15

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GeNeWatch 11

“The Farm,” reproduced with permission of Alexis Rockman

Back on “The Farm” The story behind an iconic painting and its vision of the future, a decade later

BY ROB DESALLE About a decade ago, I had the great pleasure to spend some time in the studio of a well-known New York City artist who was interested in the then burgeoning and often over-publicized science of genetic modification of animals and plants.

This inquisitive artist was Alexis 12 GeNeWatch

Rockman, a painter with a reputation among his colleagues for paintings “depicting nature and its intersections with humanity,” and “painstakingly executed paintings and watercolors of the phenomena of natural history.”

The interaction was as timely as it was interesting. Alexis knew little

about the techniques of genetic modification or genomics, but was— and continues to be—a superb natural history artist. Meanwhile, I had just begun to curate an exhibition on the human genome and genetic technology at the American Museum of Natural History entitled “Genomic Revolution.” Thus april-May 2011

began our relationship: an artist and a scientist talking every Thursday afternoon about genetic technology over coffee in his studio.

Some of the topics that Alexis wanted to discuss seemed pretty bizarre.

However peculiar the topic, I would first try to explain the technology to Alexis and then would add an extra layer of science once we felt comfortable with the primer and its jargon.

Throughout this process, it became immediately obvious to me that as he was soaking up the material, Alexis was worried that some of the genetically modified versions of animals would impact our natural world.

After about two months of my genomics “tutorial,” Alexis dismissed me and began work on a piece of art he was later to call “The Farm.” I left the last meeting with some apprehension about the art that might come from our conversations. While I felt that Alexis possessed a firm general understanding of genetic technology, I was— and continue to be— wary of how an artist or an author might take creative license with science.

While walking in the SoHo neighborhood of New York City one fall day in 2000, I looked up at a huge billboard at the intersection of Lafayette & Houston Streets. The billboard stunned me. Erected by an organization called DNAid, it featured Alexis’ “The Farm” in all of its glory. Since I had only seen sketches of some of Alexis’ ideas, I was blown away by the immensity of the piece, by its vividness and candor. Through his strong understanding of natural history, Alexis strove to create an awareness about the existence of plant and animal ancestral forms among his audience. More specifically, Alexis wanted his audience to understand that all living organisms—not just plants and animals— have ancestral forms. To facilitate this understanding, Alexis painted certain domestic animals while including the “ancestral” versions of them. Hence, we see chickens, swine, cattle, wild mice, and domestic crops in the background of the painting. It is purposefully ironic that each of these domestic forms has

its wild form that existed probably at most 20,000 years ago, when domestication began.

In the foreground, a slew of genetically modified organisms lurk near a barbwire fence. All of these peculiar creatures came from Alexis’ thinking about the extent and limits of genetic modification. The painting includes an interesting menagerie with plants, such as tomatoes, grown in cube-like shapes; a mouse with an ear growing off of its back; a rather porcine pig with human organs growing inside it; and a large cow I can only describe as “Schwarzeneggerish.” As bizarre as the painting’s modified organisms look, they were, as Alexis suggests in the description that accompanied the piece, informed by reality.

I thought it might be interesting to look at these four modified organisms a decade later to see how wellinformed the artist was in drawing them and what their status is now. Let’s start with the geometrically bizarre domestic plants. I recall from our conversations that Alexis was already aware of “Flavr Savr,” one company’s attempt to genetically modify tomatoes to maintain freshness, but he was particularly taken aback by the possibility of genetically modifying things to change their shape. The square tomatoes in “The Farm” would be much more easily and efficiently packaged.

Alas, Flavr Savr went bust around the time Alexis produced the piece, and to my knowledge no genetically modified cube tomato has been produced.

Perhaps the most peculiar animal in the piece is the mouse with a human ear attached to it. I recall that Alexis and I had discussed the potential of using non-human animals as culturing media for human organs. In 2000, this idea was very prevalent in the news, so I didn’t label this fascination as “bizarre”; rather, I thought that his questions about the topic were timely and warranted. In fact, the pig with the human organs growing inside it was also a popular news story at that time.

The “earmouse” (also known as the Vacanti mouse) actually did not have a human ear growing out of it. The “ear”

consisted of a gob of cow cartilage grown in the shape of an ear. It was produced not by genetic engineering, but by inserting a polyester fabric that had been soaked with cow cartilage cells under the skin of an immunocompromised mouse. Pigs as donors of human organs, meanwhile, are something we may see in our lifetime. Some pig organs, including their hearts, are about the same size and have the same general plumbing as human organs, and scientists have suggested that pigs might be a good source of organs for human transplants. Like any transplantation, though, tissue rejection is an important consideration, and some genetic modification of the pigs to overcome rejection would be needed.

While this might seem farfetched— especially when Alexis produced “The Farm,” over ten years ago—the possibility has been resurrected as a result of work in 2009 in China producing pig stem cell cultures. Such cultures can be used as an easier method to genetically modify pigs to circumvent the rejection problem. A year later, Australian scientists genetically modified a line of pigs by removing a stretch of a single chromosome in order to alleviate the rejection problem and allow experiments with lung transplants to proceed.

The last animal in Alexis’ menagerie is the Incredible Hulk Cow. “Doublemuscled” cows do exist, such as the Belgian Blue and the Piedmontese.

These breeds have a defective myostatin gene which would otherwise, when expressed normally, slow muscle cell growth in a developing cow.

However, these breeds came about through conventional breeding, not genetic modification. To my knowledge, super-muscular cows have not been successfully engineered, although researchers are working on several other bovine genetic engineering tricks, including cows with altered genes to improve the conversion of milk to cheese or engineered for resistance to mad cow disease.

While only one of the bioengineered animals in Alexis’s menagerie still exists today—pigs being developed as continued on page 23

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GeNeWatch 13

Top left: A fruit fly genetically engineered to grow only one eye Top right: The “Vacanti Mouse,� an immunocompromised mouse supporting an ear formed from cow cartilage Left: A flourescent piglet (left) alongside a normal one Bottom left: ANDi, a rhesus monkey engineered to glow under a UV light Bottom right: Dolly, the first cloned sheep

14 GeNeWatch

april-May 2011

topic update

Federal Circuit Hears Appeal in Myriad Gene Patent Case In front of a packed courtroom on April 4th, the Court of Appeals for the Federal Circuit heard arguments in Association for Molecular Pathology v.

USPTO. This potential landmark case in patent law challenges the patents held by Myriad Genetics, a biotechnology company, on two human genes related to breast and ovarian cancer.

The American Civil Liberties Union and the Public Patent Foundation filed suit in 2009 on behalf of researchers and women claiming that such patents wrongly restrict science and make it difficult for women to gain vital medical care (CRG has filed an amicus brief in the case). During the past 30 years, the U.S. Patent and Trademark Office has issued more than 50,000 patents related to genes in humans, animals, plants, bacteria and others. A final opinion in the Myriad case could likely determine whether patents connected to naturally occurring genes can be granted by the federal government.

Before reaching the merits of the arguments, the three-judge panel spent a significant amount of time exploring the procedural question of whether they had jurisdiction over the case— specifically, whether the plaintiffs had demonstrated that they had standing to sue. U.S. law requires that the parties to an action have a sufficient connection to and harm from the action challenged to support that party’s partici-

pation in the case. Plaintiffs urged that several individuals and groups had demonstrated sufficient likelihood of injury to confer standing. The panel expressed some concern that such a finding might allow any customer wanting access to a cheaper product to be able to challenge a patent.

Turning to the merits, the panel entertained arguments from both the U.S. government as represented by the Solicitor General (the US Government had earlier filed a friend-of-the-court brief asserting that patents issued by the PTO covering isolated DNA are invalid), as well as from representatives of the litigants. The Solicitor General asked the judges to imagine a magic microscope that would allow them to gaze into and through everything in nature, arguing that no company can legally claim ownership over anything seen though such a lens. The ACLU attorney noted that isolation cannot be the test for patentability declaring: If a surgeon cuts me open, and slices out my kidney, and takes it out and holds it in his hand, it’s an ‘isolated’ kidney, but it’s still a kidney. It’s not an invention.

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

him: To me, at least, it is an important question as to how preclusive your patent—and any other patent on any particular gene—would be if, in effect, you have to get 100, 200 or 1,000 licenses before you can sequence the genome of an individual.

The judges generally struggled to identify any kind of patent eligibility test. Patentable compositions of matter must be different in kind from those that are naturally occurring. Judge Lourie, who appeared the least impressed by the ACLU’s claims, came the closest by exploring a test centering on whether covalent bonds are broken.

He noted that breaking those bonds changed the composition of an isolated strand of DNA from its counterpart in the human body. The ACLU argued that isolated DNA is identical to DNA, and stated that all Myriad did was “snip the gene.” Judge Lourie reined in that argument, arguing that isolating DNA was “not research by tweezers.”

How the court will actually rule is impossible to predict, but an opinion is expected by late summer. Whichever way the court does rule, it is a certainty that the losing party will appeal to the Supreme Court for a final determination.

continued from page 11

As GTC and other companies scale up production herds, are there likely to be opportunities for independent farmers to start their own herds or manage a contract operation, or are companies more likely to keep production confined to their own secure sites?

Due to the rigors imposed (e.g. extensive and on-going documentation requirements) by regulatory authorities, we believe that it is highly unlikely that these activities will be contracted

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out to independent farmers.

What other techniques or products would you consider to be “the competition?”

As you mentioned, cell-based fermentation production technologies are currently used for the production of many therapeutic proteins.

Unfortunately, that technology is a very inefficient system for many proteins, unable to produce other proteins, and where it is employable it does not offer

the “scalability”—the ability to increase production easily and inexpensively— of transgenic mammary gland protein production.

GTC has an issued U.S. patent broadly covering the production of therapeutic proteins in the mammary glands of mammals until 2027, and thus does not foresee any near-term direct competitors.

GeNeWatch 15

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 Within a matter of weeks in early 2003, severe acute respiratory syndrome (SARS) spread from the Guangdong province of China to rapidly infect individuals in some 37 countries around the world. The brief epidemic infected more than 8,000 people and killed nearly 800, almost 10% of those infected. Fortunately, timely public-health actions, such as isolation of victims, stopped SARS before it became a world-wide epidemic. It is gone from nature, at least for now. We dodged a world-wide epidemic.

But SARS lives on, imprisoned in BSL3 and BSL4 laboratories around the world, and has already escaped more than once through infected lab workers. If we experience another SARS epidemic, many scientists feel that it will have started from a laboratory escape.

An escape of a highly contagious pathogen from a lab in a city is more likely to seed an epidemic; and this time, we may not be able to dodge it.

What if a lab researcher is infected with a highly contagious deadly disease that is transmitted by casual contact, a victim’s cough or from contaminated surfaces? Besides SARS, the 1918 pandemic flu also comes to mind. The Boston University National Emerging Infectious Disease Laboratory likely will research SARS and the 1918 pandemic flu.

Under the reasonable assumption that employees tend to live near where they work, the probability of an epidemic would be far greater from an infected employee living and working in or near Boston. For instance, the number of casual contacts with strangers will be sizeable for an infected researcher taking public transportation, a likely way to commute.

Transmission of infection to others, 16 GeNeWatch

called secondary infections, would be almost impossible to trace. For a laboratory located in the suburbs or rural area, most employees would drive, so their daily casual contacts with strangers would be fewer, and there is at least some chance of tracing others exposed.

Tetra Tech, a world-wide consulting firm, was hired by the National Institutes of Health to carry out yet another risk analysis for the BU NEIDL. The analysis is in progress.

This is BU’s third attempt at a believable risk analysis for their lab. It is worthwhile to review the history of risk assessments for the BU lab.

Attempt number one: This 2004 risk analysis considered only one accident scenario and only one pathogen, a small anthrax spill in the laboratory. A number of lawsuits brought by residents of Roxbury, the largely AfricanAmerican Boston neighborhood and the site of the NEIDL, challenged the certification of the risk analysis by the Massachusetts’ Executive Office of Environmental Affairs (EOEA). In 2006, a Superior Court judge deemed the certification “arbitrary and capricious” and ordered the BSL4 laboratory not to open until an acceptable risk analysis was carried out.

Attempt number two: The NIH then set out on its own risk analysis, which it unveiled in 2007. The analysis was comprised of fifteen pdf files—with dozens of photographs, drawings, graphs and statistics—that gave the impression of a precise and effortladen risk analysis. But it takes only a quick scan of the many files to realize that the whole analysis was set up to give the answer BU wanted, namely that the inner city Roxbury location for the lab was acceptable, not only acceptable but the safest location for the lab-

oratory.

Here is how NIH reached this suspect conclusion: As ordered by the Superior Court, they did consider alternative sites in Massachusetts besides densely populated Roxbury, namely Tyngsborough (a BU-owned suburban site) and Peterborough (a BU-owned rural site). The deadly and contagious viruses chosen for the analysis were ebola, sabia, monkeypox and Rift Valley fever. These choices addressed another criticism of the first risk analysis that no contagious pathogens were considered. (Anthrax is not contagious.) So far, all fine and good.

These are all “exotic” viruses (to use the NIH terminology) but represent no present or likely future public-health threat to the United States. The only scenario that NIH chose to analyze was a single researcher infected at work with one of the four exotic viruses, and then bringing his/her infection home.

The viruses are only mildly contagious, so intimate contact is required for transmission. Symptoms appear quickly so patients can be diagnosed and precautions taken, unlike the HIV/AIDS virus that can silently infect large numbers of victims without anyone being aware.

Since the viruses would likely infect only family members, health care providers and others in intimate contact with the initial victim, the number of secondary infections would be similar no matter where the victim lives or works, so population density at the victim’s home or laboratory workplace would not much matter. NIH asked only the question that would give them the answer they wanted. Location is nothing, to reverse the common realestate mantra.

But how does urban Roxbury april-May 2011

become the safest site? The answer lies in Rift Valley fever virus, which is transmitted by mosquitos from cattle and other farm animals to humans.

Even though many of Boston’s streets were laid out by cattle in colonial times, there are no cattle there now. So Rift Valley fever virus would infect more people in suburban or rural settings where farm animals live. Urban Roxbury then becomes the safest place for the NEIDL compared to suburban and urban locations.

Between the first and second riskanalysis attempts, Massachusetts changed governors from Mitt Romney to Deval Patrick and the management of EOEA changed as well. The new EOEA folks made a smart move. They realized that they did not have the background to understand the issues, so they asked the National Academy of Sciences to appoint a National Research Council (NRC) committee of experts to critique the risk analysis.

The NRC committee delivered their detailed critique in late 2007, concluding that the NIH analysis was not sound and credible, that the worst case scenarios had not been adequately identified, and that the information underlying the alternative site analysis was insufficient or inappropriate. The critique also questioned the infectious agents selected.

Now back to the in-progress Tetra Tech risk analysis. Tetra Tech presented its preliminary results to local residents at the Roxbury Community College in October 2010. Among its findings was that a secondary infection of SARS to someone outside the lab from a lab researcher would occur VoluMe 24 NuMber 2

once in 10,000 years in a worst-case scenario, and likely only once in over a million years. Tetra Tech looked at only two scenarios, a centrifuge accident and a massive earthquake that would level the laboratory. They did not look at the risk of a SARS-infected lab worker, unaware he/she was infected, transmitting the infection to someone outside the laboratory.

The NRC committee commenting on the Tetra Tech preliminary work concluded “at this point in time it cannot endorse the illustrative analyses presented as scientifically and technically sound or likely to lead to a thorough analysis of the public health concerns previously raised by the NRC.” The committee also noted “Consideration of the available case studies (such as the SARS case described below) suggests the possibility that transfer of a pathogen outside the laboratory by an infected worker is an important class of risk events.”

There have been at least three SARS escapes from laboratories through infected lab workers. The incident from the NRC 2010 document quoted below warns of the danger of a future SARS escape in a densely populated area.

“In China, SARS/CoV was grown in a BSL-3 laboratory by a worker who apparently had worn inappropriate personal protective equipment (PPE) and then treated the sample to inactivate the virus before removing it to a BSL-1 laboratory for further work on the open bench. The worker failed to verify the complete inactivation of

the virus and subsequently became ill and was admitted to a fever hospital. The laboratory was not notified of this development and the worker later returned to the laboratory. A second worker who handled the “inactivated” sample also became ill. A graduate student who observed the laboratory procedure later traveled by train to her home several hundred miles away.

After returning to the laboratory she became ill and once again traveled to her home by train where her mother, a physician, admitted her to a hospital and treated her.

The student was asked if she worked with SARS/CoV (she said no because her research involved another virus). It was not until the mother became ill and died that SARS/CoV was identified. Other laboratory workers also became ill and other hospital personnel died.

This case study illustrates several important points: people make mistakes (improper PPE); not everyone follows procedures (failure to test sample for inactivity); people may die if not properly diagnosed and treated.”1

Another message from this story is that research on deadly, highly contagious pathogens should be conducted only in BSL4 laboratories in isolated locations where extra precautions in addition to location are available, never in a populated area since SARS has also escaped from a BSL4 laboratory.

How many bites of the apple will Boston University have before they realize that a BSL4 Laboratory in densely populated Boston is a bad and dangerous idea? When will the city or state step up and say “No! No BSL4 lab in Boston,” following Cambridge’s lead?

Lynn C. Klotz is co-author of Breeding Bio Insecurity: How U.S. Biodefense Is Exporting Fear, Globalizing Risk, and Making Us All Less Secure. He is working with scientists and Roxbury residents to propose an alternative vision for the Boston University labs.

GeNeWatch 17

Gene Patenting in Canada From the oncomouse to cancer gene testing and beyond

BY JAMES J. RUSTHOVEN

AND THE OF THE

The recent decision by United States District Court Judge Robert Sweet to invalidate seven patents on the BRCA breast cancer genes held by Myriad Genetics is a monumental decision (though the decision is being appealed as expected).1 Coupled with the subsequent U.S. Justice Department amicus brief arguing against the patenting of naturally-occurring genetic material,2 these events have triggered advocacy groups from other countries such as Australia to consider its own legal action to restrict DNA patentability laws and policies.3 The pendulum now may be swinging away from internationally-accepted, broadly interpreted and applied gene patenting practices toward tighter rulings against the patenting of naturally-occurring genetic material.4 In this changing climate, we offer a perspective on the current state of gene patenting in Canada.

The case of the Harvard oncomouse put Canada front and centre in gene patenting law and policy-making.

United States patent approval for exclusivity rights to the oncomouse was granted in 1988. After eight years of governmental and legal reflection and decisions, at the end of 2002 the Supreme Court of Canada (SCC) denied the patent on genetically-modified (GM), entire non-human mammals including the oncomouse by the narrowest of margins.5 The five judge majority argued that a mouse does not qualify as a “manufacture” or “composition of matter,” the terms used in patent law 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 5-4 margin that a patent protecting commercial rights to GM cells in canola plants also could impart de facto exclusive rights over the entire plant.6 The majority argument hinged on the concept that patent infringement could be

18 GeNeWatch

construed involving a whole organism if a commercial or business activity involving an organism with a patented gene or cell necessarily involves using that patented part. This decision seems to conflict with the earlier oncomouse decision against patent protection of the entire mouse.

These cases reflect an as-yet-unresolved debate and societal tension regarding biological, ethical, economic, and political aspects of human interventions involving life forms in Canada.

Arguments have sometimes alluded to extra-legal effects on capital investment and international economic competitiveness, at times at the expense of sound legal reasoning.7 It should be noted that in both cases, the SCC rejected the broad, carte blanche type of whole organism patenting granted in the United States. However, as a result of the Schmeiser vs Monsanto decision, the legal status of whole organism patenting in Canada lacks clarity on the basis of such inconsistent case judgments by the highest court of the land.

In the meantime, the momentum to commercialize genomic research continues unabated in Canada and elsewhere. Our knowledge of the full complement of genes of a growing number of whole organisms is growing rapidly and whole genomes are now being reconstructed through synthetic biology techniques. Research melds with commercial ventures through increasing university/industry collaborations.

Despite these developments, there remains no practical guidance for researchers and policy-makers on the ethical implications of privatization and commercialization of bioresearch beyond the general ethical framework of the Tri-Council Policy Statement.8 In recent qualitative studies, researchers have expressed more concern over increasing secrecy, publication delays, and increasing numbers of material

BIOTECHNOLOGY REFERENCE GROUP CANADIAN COUNCIL OF CHURCHES

transfer contracts than over patenting, commercialization, and conflicts of interest.9,10 Societal Imperatives: Healthcare Access versus Private Commercialization of Healthcare Resources In Canada, the narrow margin of SCC decisions of the above cases may not only reflect discordant legal views on patenting life forms but also ongoing societal differences of worldviews over the relationship of humankind with the natural order. In the past, The Canadian Council of Churches and the Evangelical Fellowship of Canada have argued that higher life forms should not be patentable on the grounds that humankind has a God-given responsibility to care for the created order.11 In this worldview, privatization and commercialization of life forms threatens that overarching mandate. The recent paradigm-changing decision to strike down the Myriad patents on naturallyoccurring breast cancer-associated genes suggests that such a view may be regaining support at the highest government and societal levels in the US (as suggested by the amicus brief noted above), the country that granted the broadest patent protection for the oncomouse patent.

Notwithstanding the seemingly contradictory judgments by the SCC over whole organism patenting, the recent drama played out over the Myriad patents has somewhat ironically positioned Canada as an advocate against “natural” single gene patenting. Unlike the oncomouse and GM canola cases, however, the Myriad case impacts on public healthcare access to necessary diagnostic testing, bringing a new and more ominous societal danger to the concerns over ‘anti-commons’ issues in Canada.12 It also brings into sharper focus the societal and political forces

april-May 2011

that drive arguments for the various tioned is an element of whole organism clarify patent laws requires political positions. Legally, in the judgment of patent protection that is often over- wisdom through a clear picture of the Industry Canada’s Patent Office looked: patent protection coverage for multiple societal values, interests, and Directorate, Myriad Genetics did not the offspring of such whole organisms risks. Some analysts have argued for violate Canada’s patent or competition over the life of the patent. The intro- better societal and moral guidance laws.13 Industry Canada even chal- duction to the discussion guide through a new research framework that lenged the government of Ontario to includes an appeal to the Canadian replaces commercialization with the provide evidence that gene patents Parliament to develop laws that direct- broader perspective that considers deterred research as well as evidence ly face the question of whole organism implementation of research knowledge that it could not obtain a compulsory patentability. including the full breadth of societal license to override Myriad’s patent Have the Harvard oncomouse deci- implications.20 Others have proposed monopoly on BRCA gene testing.14 sion and the subsequent landmark an independent governance entity that Politically, both Myriad’s case and cases resulted in any concrete changes would oversee commercialization that of provincial and federal govern- to gene patent law or practice in through patent pools and open source ments suffered from miscommunica- Canada? After years of intergovern- strategies that would facilitate access to tions and misjudgments.15 Federal and mental jurisdictional and political patented inventions. Such initiatives provincial governments debated over wrangling, the Patent Policy would aim to restore public trust who should solve the gene patenting Directorate and Health Canada finally through better integration of diverse problem, ministries could not agree on agreed to consult directly with public voices and the consideration of the problem or its solution, and Canadians through the independent broader social and ethical issues.21 For its part, The Canadian Council of provinces varied in their decisions to Canadian Biotechnology Advisory comply with or resist Myriad’s exclusiv- Committee (CBAC). Regrettably, near- Churches continues to oppose patentity claims. Analysts argued that much ly all of its recommendations have been ing of life forms and commercial of the government response and tactics ignored; CBAC was disbanded a few exploitation, promotes open exchange of research ideas for were fuelled by negathe common good of tive press against Myriad’s bullying tac- “Government action against single gene patenting may humankind and the created order around tics16 and its attemptbe driven more by perceived direct threats to the ed displacement of us, and supports the the public system’s publicly-owned and operated healthcare system than formal integration of pre-existing gene public voices that to any government change toward a broader testing program that consider the full included patient impact of genetic moral view of the dangers of patenting life forms.” counseling.17 Studies technologies on the identifying public various aspects of concern about the potential for gene years ago, its mandate taken up by the societal life in Canada. The Council patenting to limit healthcare accessibil- Science, Technology, and Innovation lauds individual legal decisions that go ity to poorer citizens bolstered govern- Council of Industry Canada. After against international currents that ment refusal to bow to corporate intim- more than seven years the federal gov- Canadian governments deem socially idation.18 Thus, government action ernment continues to simply ignore and morally dubious or wrong. But it against single gene patenting may be patents while provinces are confident also continues to urge the establishdriven more by perceived direct threats that they sent a clear signal that com- ment of proactive legal and moral guidto the publicly-owned and operated mercialization of necessary healthcare ance that reflects the diverse moral senhealthcare system than to any govern- resources will not work in the Canada. sitivities of Canadian society and gives ment change toward a broader moral This strategy may have recently direction to the improved overall view of the dangers of patenting life deterred one recent Canadian licensee health of Canadian society. Life is forms. of another patented gene from attempt- given as a gift from God, for us to both ing to enforce its exclusivity rights. enjoy and to respect.

Has Anything Changed?

Instead, the company has sold kits to At the time of the oncomouse public laboratories.

Supreme Court decision, the The failure to heed the exhortation to Members of the Biotechnology Reference Biotechnology Reference Group of the provide guidance for future investors in Group include: James Rusthoven (chair), Canadian Council of Churches created Canadian genetic bioresearch through Moira McQueen, Stephen Allen, Anne a discussion guide of short essays (Life: legal changes has left the problem in Mitchell, Erin Green, Richard Patent Pending) that highlights a num- continued legal as well as moral limbo. Crossman, James E. Read, Paul Fayter, ber of fundamental concerns over the Admittedly, the problem is a politically George Tattrie, Mark Boulos, Isaac patentability of whole organisms that difficult challenge to Canadian govern- Kawuki Mukasa, Emanuel Kolyvas, are mentioned above.19 Also men- ments. Any attempt to tighten and Peter Noteboom, and Mary Marrocco.

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GeNeWatch 19

Unnatural Selection More and more parents around the world are gaining the ability to choose the sex of their child. Now what?

INTERVIEW WITH

Mara Hvistendahl is a correspondent with Science magazine and author of Unnatural Selection.

Where did you get the idea for this book?

I was researching sex-selective abortion in Asia, and mostly unaware of developments with in vitro fertilization (IVF). But setting up to write this book, I was really determined to find a way to make it relevant for readers in the U.S., and I didn’t want them to come away with this message that people in China and India are sexist, and that’s why they abort girls, or that it’s this problem that only happens in other countries. Later, I uncovered this whole connection with the population control movement in the U.S. in 1960s America, so there actually was a pretty direct link. Ultimately, I ended up visiting fertility clinics in California. I visited The Fertility Institutes and Jeffrey Steinberg, one of the most notorious people doing pre-implantation sex selection in the U.S. Is pre-implantation sex selection happening very much in the U.S.?

Initially, PGD (pre-implantation genetic diagnosis) was just used for couples who had a genetic propensity toward a disease linked to the sex chromosomes. For example, if a woman is carrying the gene for hemophilia, by sorting for girls, she can guarantee not having a child with hemophilia.

Mark Hughes, who was very involved in developing pre-implantation sex selection in the U.S., didn’t think couples would go through IVF and PGD just to get a child of a certain

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sex. IVF is really intensive, it’s really expensive, and there isn’t even a high success rate. Together with PGD, it can cost something like $18,000; so it makes sense to assume that people wouldn’t want to do that just because they want a boy or a girl. But he was wrong, and Jeffrey Steinberg started offering this service and got a lot of publicity. He also provides IVF for people who can’t have a baby otherwise, but he says that now 70% of his business is from people coming to him because they want a boy or a girl.

There are other fertility clinics that won’t offer sex selection to just anybody. A lot of clinics will provide it if it’s for “family balancing.”

Right—the American Society for Reproductive Medicine said, “physicians should be free to offer pre-conception gender selection in clinical settings to couples who are seeking ‘gender variety’ in their offspring.” In other words, they approve of sex selection for someone who only has children of one gender and want their next child to be the opposite gender. How do you police that?

The main problem with assisted reproduction in the U.S. is that it’s not well regulated, and even the ASRM guidelines are voluntary.

There’s another kind of sex selection called MicroSort. It’s sperm selection, really: you spin the sperm in a centrifuge, and because sperm carrying the X chromosome are heavier—they are carrying more genetic material— they separate out from the ones carrying Y chromosomes. There have been trials for that going on for years, and in that case the clinics are only allowed to admit a patient who has a child of the

opposite sex.

But what struck me in writing this book is that this really isn’t very different from what parents are doing in Asia. In China and India, they’re typically not aborting female fetuses the first time. Most people wait until they already have one girl, and then for the second child, they go and get an ultrasound and abort if it’s another girl.

Didn’t India and China both ban ultrasound testing for the purpose of sexual selection? Although I don’t know how well that’s enforced …

It’s not enforced. There have been some crackdowns, and I actually think when governments really crackdown it can be effective, but it’s not really enforced.

How do people get around those laws?

In China, people told me they bribe the ultrasound technician. In India, the clinics are supposed to register every woman and to keep track of births, whether each baby was a boy or a girl, but they often don’t have very complete records.

But you could argue that in a way, there’s more extensive regulation in Asia than in the U.S. Although PGD is starting to be introduced in Asia, and there aren’t strong regulations for that.

What technologies are being used for sex selection in other parts of the world?

In most of the developing world, it’s

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health care improves, and women have access to ultrasound.

How significant is the sex ratio imbalance globally? Are there places where it’s particularly imbalanced?

It’s spreading, actually. It’s significant enough now that the global balance is slightly skewed—it’s now 107 boys per 100 girls, when it had been more like 105 to 100.

Demographers are watching, but it’s difficult to predict which countries will be next. Most people didn’t expect it in the Caucus countries—Azerbaijan, Armenia, Georgia—and now in the Balkans, in Albania, Montenegro, maybe Macedonia. done through an ultrasound scan to determine the sex, then abortion if it’s a girl. One demographer told me that accounted for 99% of sex selection in the developing world.

How does the prevalence of sex selection differ between developed countries 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 PGD usually want girls; but generally, the preference for boys is pretty universal.

The situation changes when the fertility rate starts to fall. When you are having five or six kids, there’s a good chance that one of them is going to be a boy. When you’re only having one or two kids, you don’t have that guarantee. Even in countries that don’t have a one-child policy, people are still having fewer kids. In India, women are having only two kids, maybe one in Delhi. In Albania the fertility rate is just over one child per couple. So there’s more pressure on women to have a son, some of it self-imposed.

This happens when the fertility rate drops dramatically in a country—and when abortion is legal, or at least available. I connect it to economic development, because fertility rates tend to go down as countries develop, and at the same time new technology comes in, VoluMe 24 NuMber 2

It’s not hard to see where the imbalance could become a really serious problem when everyone is only having one child, and everyone is making sure that one child is a son.

How serious is the gender imbalance in those countries?

There’s some disagreement, but in Albania it’s around 110 boys for every 100 girls. In Armenia it’s even higher. It won’t be around forever in those countries—most demographers believe it’s a transition phase that countries are going through as they develop, and eventually they start having more girls—but it may take several decades to get to that point.

What is it that changes to make people no longer feel that they have to have a son?

The only place where there was a gender imbalance but the birth rate has now evened out is South Korea; but the birth rate has also dropped so low in South Korea that people are hardly having any kids. It was the lowest in the world a few years ago. People I talked to there didn’t really feel that gender discrimination had gone away; it’s more a matter of people not having many kids, so it doesn’t really cancel out the decades of sex selection before it.

In the U.S. the preference for girls is

interesting. Fertility clinics say that most couples go in for girls, although it’s not hard data, since they don’t have to report either how many couples are going in for sex selection or how many kids are being born through those methods. People give all sorts of reasons for wanting girls. Some say they want to raise a strong daughter, that they want to raise the first female president, or that girls do better in school now. There are also some people with more sexist ideas, wanting to have princess parties and that sort of thing.

Sex selection, and a lot of these almost eugenic choices, come up against the way that reproductive rights have been framed in the U.S., which is around this principle of choice: that a woman should have the right to choose when to terminate a pregnancy. But to some degree that’s been extended to include the idea that she should be able to choose what kind of child she wants. So there’s a need to reframe that debate around something other than “choice.” It just doesn’t work anymore for issues like sex selection.

Some bioethicists propose instead looking at the right of a child to not have his or her fate determined before birth.

It doesn’t seem like very many groups are trying to navigate these issues for fear of confusing their message about abortion rights.

What I found in researching this book is that some reproductive rights organizations won’t even address the gender imbalance because they don’t want to deal with abortion. As a result of that, a lot of people in the west don’t really know about it. That’s not the answer. I think we need to reframe the debate around something other than just “choice.”

To me, the right of a child to an open future makes sense. It’s not that you’re calling for fetal rights, you’re not talking about the embryo as having rights, but the child that is born later should have the right not to have all these expectations foisted on him or her.

It’s a difficult question, but I don’t think we benefit at all from steering clear of difficult questions.

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Sacred Grounds A community of “The Last Incas” bristles at National Geographic’s attempt to collect their DNA

BY SAMUEL W. ANDERSON

The Q’eros, an indigenous community of the Peruvian Andes, identify themselves as “the last Incas.” The Q’eros people fashion their way of life, their traditions, their belief system— their very existence—on their Inca heritage.

How did the community react when researchers from the National Geographic Foundation’s Genographic Project offered to use DNA testing so that “the people of Q’eros can know their ancestral roots?”

As you might expect, there was some backlash.

“The Q’ero Nation knows that its history, its past, present, and future, is our Inca culture, and we don’t need research called genetics to know who we are,” wrote Benito Machacca Apaza, president of the Hatun Q’eros community, in a letter asking the regional government in Cuzco to prevent the Genographic Project from entering their communities to collect samples.

“We are Incas, always have been and always will be.”

“It is disingenuous to presume, as the Genographic Project has, that indigenous peoples’ origin narratives and the genetics narratives will peacefully coexist in parallel,” says Alejandro Argumedo, Research Director for Asociación ANDES, a Cuzco nonprofit concerned with protecting the rights of indigenous peoples.

“We believe that the Genographic Project is blinded by its own ambition.

We don’t believe that it came to Cusco with malice in mind, but its intentions are wholly self-serving.”

Part of the groups’ indignation stems from a letter which Asociación ANDES 22 GeNeWatch

says a representative of National Geographic sent to the Hatun Q’eros community, encouraging the community to come to a presentation where seven people from National Geographic would explain the Genographic Project and seek participants. “Everything is voluntary, there is no obligation,” the letter assures, “but you are going to have fun and learn a lot!” The letter also promises that the presenters “will use a projector and beautiful images!”

The Hatun Q’eros’ are concerned with protecting more than their pride and self-identity, though.

“The Q’eros, and for that matter many other indigenous peoples, are facing outside pressures on their land from extractive industries,” Argumedo says. “If the Genographic Project were to, for example, claim that the Q’eros were migrants to the Andes from the lowland forests, this information could be used by mining interests to bolster their argument that they should be granted rights by the Peruvian government to extract minerals from Q’eros territory. In fact, although it was not mentioned to the Q’eros, the Genographic Project even says on its website that it wants to study genetic links between the Q’eros and lowland peoples.”

Of course, participants have the option of simply refusing to give samples. The concern, says University of California at Berkeley professor Kimberly TallBear, is that potential participants have the opportunity to make an informed decision. The Genographic Project addresses this in their code of ethics, where it affirms

that informed consent in the project must be “deliberate, considered, individual and collective.”

The initial letter cited by the Hatun Q’eros does not appear to meet the Project’s standards. “To the contrary, a one-page flyer with patronizing language was delivered to the community not long prior to the planned DNA collection,” TallBear says. “A powerpoint presentation was planned immediately prior to DNA collection. This allows no time for community input to the research process, nor for real collective consent as collective discussions take considerably more time than individual discussion and consent.”

National Geographic spokesperson Lucie McNeil tells it differently.

“Our South American team has been undertaking outreach and sampling work with Peruvian leaders, communities and individuals since September 2007,” she told GeneWatch. “Our reception has almost uniformly been very positive, and the Peruvians we have contacted are keen on having access to other ways of learning and adding to their knowledge of their own history. “ As for the Q’eros?

“We have been reaching out to the Q’eros communities since 2009,” she says, and had learned that “verbal per-

april-May 2011

mission of a mayor to come to his community is the necessary step before any sampling takes place.” McNeil stresses that “only outreach has taken place in the Q’eros community”—no samples have been collected yet—and that “we were not planning to visit” the Qocha Moqo community, which filed the complaint. The letter that spurred the controversy, ostensibly from a representative of National Geographic, suggests otherwise, specifically addressing the Qocha Moqo community. National Geographic has declined to comment on its knowledge of the letter or its authenticity.

McNeil says that the Hatun Q’eros at

Qocha Moqo were the only Q’eros community to file a complaint, and that the mayors of nearby Q’eros communities Ch’allmachimpana and Chuwa Chuwa had already given the Genographic Project verbal permission to visit. The Project cancelled their visits to those communities after the mayor of Qocha Moqo filed his complaint. “We received immediate word from the communities of Ch’allmachimpana and Chuwa Chuwa that they are very disappointed that we were not able to visit them,” McNeil says. “We have heard they are also disappointed with the Mayor of Qocha Moqo for filing the complaint on their

behalf - apparently Q’eros protocol requires him to discuss this with the other communities first.”

Both sides say that they have yet to contact each other directly. In the meantime, McNeil says, “Our South American team continues to work successfully with other communities in Peru. Engagement of around 90 Peruvian communities has taken place and we have 1060 samples.”

Don’t expect the Q’eros of Qocha Moqo to join them.

farmer in upstate New York. Over a beer in the shade of a barn, we were talking about how farming has changed since he was a young man.

During the conversation, I excitedly tried to explain to him the possibility of using plants with a genetically engineered gene involved in stress tolerance. This gene would be linked to a luminescent beacon, so that when the plants were under drought stress, the beacon would glow, telling the farmer to water it. My uncle looked at me incredulously and said, “Now how good of a farmer would I be if I couldn’t tell my crops needed water?”

Rob DeSalle, PhD, is a curator in the American Museum of Natural History's Division of Invertebrate Zoology and co-director of its molecular laboratories and a member of CRG’s Board of Directors.

Samuel W. Anderson is Editor of GeneWatch.

continued from page 13

organ donors—ten years later, Alexis’s “The Farm” still makes a compelling statement about technology and nature. We are in the midst of our second generation of genetic modification (the first being the initial domestication of plants and animals), and we have not yet figured out how to proceed. Alexis draws attention to the fundamental novelty of genetic engineering in depicting the progression of domesticated animals as beginning with already-domesticated forms, subtly omitting their wild ancestors.

All of this reminds me of a conversation that I had with an uncle who is a

25 Years of GeneWatch GeneWatch Anniversary Archive: 1983-2008 The Council for Responsible Genetics was founded in 1983 to provide commentary and public interest perspectives on social and ecological developments of biotechnology and medical genetics. For a quarter of a century, the Council has continued to publish its magazine GeneWatch with articles by leading scientists, activists, science writers, and public health advocates. The collection of GeneWatch articles provides a unique historical lens into the modern history, contested science, ethics and politics of genetic technologies. The full archive of GeneWatch has been incorporated into this special anniversary DVD that includes an index of all the authors and titles.

Copies of the anniversary DVD are available for a $100 donation to: Anniversary CRG DVD Council for Responsible Genetics 5 Upland Rd., Suite 3 Cambridge, MA 02140

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Musical Genes The Genetic Music Project encourages musicians to convert DNA code into music INTERVIEW

Greg Lukianoff is a founder and the curator of the Genetic Music Project, a community art endeavor in which musicians convert genetic code into songs. Greg volunteered pieces of his own code, taken from test results from consumer genetic testing company 23andMe, uploading them to the website for musicians to use as a starting point. Although musicians are free to get more creative about the way they convert the genome into music, the first few songs on the site assign a note to each of the four nucleotides (A, C, T, and G); pick a FASTA sequence (which uses those four letters as a shorthand way to express a piece of genetic code) associated with a certain trait (such as likelihood of baldness or schizophrenia); and just see what series of notes emerges.

When Greg spoke to GeneWatch in May, the Genetic Music Project had been live for less than two weeks—and he had already received a song from a stranger in Denmark. To learn more about the project, listen to the songs, and even upload your own music, visit www.geneticmusicproject.com.

The process starts when you get a genetic test—yours was from 23andMe—and when you get the results back, you select a chunk of the genetic code and assign a note to each of the four nucleotides. What does that first piece of code look like? What does it represent?

The genetic test is selecting the FASTA sequence for certain genetic markers [see diagram on facing page].

What you’re getting back is, to the best of my knowledge, the entire FASTA

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sequence for an allele. So I put that up there, and I indicate what conditions those alleles are associated with— which provides a lot of opportunities for metaphor and tone for the music that people submit.

For instance, when I found out that there was a particular genetic marker for bitter taste perception, I found the FASTA sequence for it, put that up, and sent it to my friend Amy, who is an unbelievably talented country artist. If someone was going to sing a song on the theme of “bitter,” who better than a country singer?

I was really surprised that nobody had already made a community art project out of genetic sequencing. I knew that people had been making music out of genetic code—for example, the composer Alexandra Pajak wrote an album based on the sequence of the HIV virus—but given that DNA is part of this wonderful organic system that grows by its own nature, that seems to be perfect for a community art project, something that you just put out into the world and see how it does.

Of course, there’s an element of unnatural selection to it—I’m curating the website—but at the same time, I don’t know where it’s going to end up.

You provided the code; who writes the music?

When the site first went up, pretty much all of the music came from friends of mine who were excited about the idea. Having someone in Denmark upload a song was something else. My big hope is that it continues to grow, and that people recognize that you can go well beyond taking the four individual “notes” from the nucleotides (A, C,

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GREG LUKIANOFF

T and G).

Using the computational brilliance of genetics, you can create more and more complex art. The different nucleotides could stand for pitch, or you could even take a bunch of nucleotide sequences and relate that to the 64 different settings of a Casio keyboard and let the code tell you which instruments to use. So there is a tremendous amount of fun to be had with this, and hopefully it will grow organically.

I’m particularly interested in getting different genres of music, too. I’d really love to get a rock song, for example. I think when people think of ‘genetic music,’ they would first think of some sort of atonal electronica, but as we’ve already shown, it can work out in so many musically interesting ways.

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

I think you could figure out a way to make any genre work. The only genre I’m not interested in hearing is smooth jazz. Because smooth jazz is terrible.

But with real jazz, I actually think that the surprising twists and turns of the FASTA sequences would be perfect for jazz saxophone.

One of the things about the musicality of the genetic code is that it does surprising things. For example, the piece on heroin addiction is just based on the first ten nucleotides of the FASTA sequence for a gene that is supposed to indicate that you may be more easily addicted to heroin. When she played that, just the first ten nucleotides, it was really haunting.

Then it can start to get interesting, where you can stumble into themes. It

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sounds very traditional, but then it will run maybe one or two notes longer than you would expect. You end up hearing some surprising musical things come out of it.

Are you coming at this more from the science or music side?

I wouldn’t pick one or the other. I’m sort of a science hobbyist—it’s the degree that I never got but always wanted to. So I sort of came at it from the science side rather than from the music side. The inherent musicality of the information behind all life just seemed irresistible.

Have you learned more about music or genetics?

I think I’ve learned a lot about both.

There were certainly things I didn’t know about genetics, and there were plenty of things I didn’t know about music. That’s one of the things I’m trying to be open about, that I’m neither a musician nor a scientist!

The difference between this website and others, really, is that we decided to just put it out there and see what happens with it, to encourage people to be creative and apply their own approach—but also to teach everyone, including me, about the science and the music behind it.

Top: the FASTA sequence for “longevity,” as defined by 23andMe Middle: Flemming Laugaard, a songwriter in Denmark Bottom: Sheet music for “The Long Haul,” written by Laugaard based on the FASTA sequence above

I noticed that one of the FASTA sequences you posted is supposed to be the genetic marker for “longevity.” Am I right to figure you’re taking 23andMe’s test results with a grain of salt?

One of the things 23andMe does is indicate the amount of research behind the traits. For some there has been a lot of research and for some there have been only tiny studies. They’re good at explaining it, and this is something I suspect I’ll eventually be asked; but I try to make clear that I’m not vouching for the accuracy of the information, I just think it’s a great starting point.

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Massachusetts Legislature Holds Hearing on Genetic Bill of Rights

BY JEREMY GRUBER On April 5th, the Massachusetts Legislature’s Joint Committee on Public Health held a hearing to consider the recently introduced “Genetic Bill of Rights” (Senate Bill 1080). At that hearing, I testified in favor of the bill along with representatives of the ACLU and the Forum for Genetic Equity. The Joint Committee displayed a strong concern for the issues presented and indicated a renewed commitment to moving this important piece of legislation forward.

Indeed, other states are following the example. Vermont recently introduced its own “Genetic Bill of Rights” (HR 368) and declared April 25, 2011 as Genetic Equity Awareness Day. CRG is working in partnership with the Forum for Genetic Equity to advance the “Genetic Bill of Rights” (named after CRG’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 the recently enacted federal Genetic Information Nondiscrimination Act (GINA), an effort I led for fifteen years.

GINA was successfully propelled by a legislative campaign that we began in the early 1990’s to enact state protections against the misuse of genetic information in the areas of health insurance and employment. As more and more states began passing such laws, the prospects for federal legislation grew and GINA was enacted in 2008.

Beyond the protections of GINA, though, there is no comprehensive genetic privacy law in the U.S. Ten years after the mapping of the human genome was completed, the genetic revolution has led to a tsunami of DNA data created by genetics research and the commercialization of such research. And the commercialization of genetics is well underway. As more and more of this personal information

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becomes public knowledge, it can be bought and sold by any commercial interests interested in predictive information about an individual’s future health status. Current law does nothing to prohibit discrimination in life insurance, disability insurance, long-term care insurance, mortgages, commercial transactions, or any of the other possible uses of genetic information. The public must be assured that undergoing genetic testing will not endanger their economic security.

The campaign to enact a Genetic Bill of Rights is an attempt to go back to state legislatures and address this significant gap in protections for the American public. The bill sets clear limitations on the use of personal genetic information in a variety of contexts unforeseen just a short time ago including protections against the use of genetic information in workers compensation claims and for marketing or determining credit worthiness. With the proliferation of genetic information, particularly in consumer contexts, this legislation sets strong standards on the disclosure of such data and ensures that genetic information and material are treated under state law in a manner similar to other medical records and creates a duty to report in the event of known security breaches or unauthorized use of personal information.

Mistakes and other breaches of security are not uncommon. Just last year, the direct to consumer genetic testing company 23andMe accidentally sent data of up to 96 individuals to the wrong customers.

As genetic research and commercial genetics applications have proliferated, narrow ethical precepts governing human subject’s research have coupled with little to no regulation of commercialized genetics. This toxic combination has ridden roughshod over the reasonable expectations and the appropriate rights of the people whose data and materials are implicated. Take the case

of the Texas Department of State Health Services, which sent the genetic information of newborns to Texas A&M University for research without the parents consent. Some of those samples found themselves in an armed forces database.

Or consider the case of members of the Havasupai tribe, a small, isolated community who gave DNA samples to researchers from Arizona State University to contribute to research that could help determine the cause of the tribe’s very high rate of diabetes.

Nothing much came of the diabetes study, but over a decade later, the Havasupai discovered that over 20 academic articles had been published based on studies conducted at the university using Havasupai DNA, studying an array of topics the tribe members never agreed to. Many members expressed their shock at such a betrayal.

Such systematic violations of the expectations of people whose DNA, and personal health information is being used without their consent is just wrong. It’s a violation of basic human rights. Moreover, as commercialization of genetics has exploded, individuals are being the denied the inherent monetary value of such information at the same time that personal genetic information is becoming widespread and

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our understanding of such data becomes richer and therefore increasingly valuable. The Genetic Bill of Rights represents a significant step forward in giving individuals back their autonomy by granting exclusive property rights to their own genetic information. Through property rights individuals will gain a series of rights regarding the control, possession and transferability of genetic information that are unavailable through privacy legislation alone; empowering individuals to have initial and on-going control

over the use of their own genetic information. In turn, providing individuals with greater control over the use of their genetic information will, more practically, encourage otherwise reluctant individuals to participate in research by balancing their interests with the interests of those who seek to use such information for a variety of purposes.

For these reasons, we are working hard with our organizational partners to pass strong and comprehensive laws providing property and privacy rights

Endnotes Paul Root Wolpe, p. 4 1. Jonsen, AR. (1986) “Bentham in a box: Technology assessment and health care allocation” Law, Medicine and Health Care 14:172–4.

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

3. Whitehouse, D. (2002) “Here come the ratbots.” BBC News: May 1, 2002 {http://news.bbc.co.uk/2/hi/science/nature/1961798.stm} Eric Hoffman, p. 6 1. See “Fishy Business at the FDA,” from Genewatch, Volume 23 Issue 4: http://www.councilforresponsiblegenetics.org/genewatch/GeneWa tchPage.aspx?pageId=289 2. Twelve of the nation’s largest environmental groups sent an open letter to the FDA asking for an independent and comprehensive Environmental Impact Statement to be completed in place of the less-thorough Environmental Assessment, as mandated by the National Environmental Policy Act: http://foe.org/sites/default/files/Environmental%20Group%20Lett er%20to%20FDA%20-%20GE%20Salmon%20Final.pdf 3. This is an abridgment of DRAFT legislative principles for the regulation of genetically engineered animals developed by the Center for Food Safety Lynn C. Klotz, p. 16 1. “Continuing Assistance to the National Institutes of Health on Preparation of Additional Risk Analysis for the Boston University NEIDL, Phase 2,” (November 5, 2010) http://www.nap.edu/catalog.php?record_id=13054 James J. Rusthoven, p. 18 1. Schwartz, J. and Pollack, A. Judge Invalidates Human Gene Patent. 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 in Challenging Gene Patenting. GeneWebNews, Pharmacogenomics Reporter, June 15, 2010 (http://www.genomeweb.com/dxpgx/australian-patient-groups-follow-aclupubpat-path-challenging-genepatenting). Last accessed 7 February 2011.

4. Kesselheim, A. S. and Mello, M. M. Gene Patenting – Is the Pendulum Swinging Back? New England Journal of Medicine 2010; 362:1855-1858.

5. Harv1.ard College v Canada 2002.

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for genetic information and genetic material. The Genetic Bill of Rights, if enacted, would confer upon Americans a significantly expanded set of rights than exist under current law and place the United States once again in its rightful role as a leader in addressing the social and ethical implications of new technologies and biotechnologies in particular.

Jeremy Gruber, JD, is President and Executive Director of the Council for Responsible Genetics.

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

7. Prudham, S. The Fictions of Autonomous Invention: Accumulation of Dispossession, Commodification, and Life Patents in Canada.

Antipode 2007; 39(3): 417, 418.

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

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

10. Silverstein, T., Joly, Y., Harmsen, E., and Knoppers, B.M. The Commercialization of Genomic Academic Research: Conflicting Interests. 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 the Oncomouse. Available on the Canadian Council of Churches website: http://www.councilofchurches.ca/en/Biotechnology/biotechnology-resources.cfm. Last accessed 8 Feb 2011.

12. The ‘anti-commons’ problem refers to the view that the increasing number of private rights over basic biomedical information compromises biomedical research due to the high transaction cost. See Heller, M. A. and Eisenberg, R. S. Can Patents Deter Innovation?

The Anticommons in Biomedical Research. Science 1998; 280: 698701.

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

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

15. Ibid, S52.

16. Caulfield, T., Bubela, T., and Murdoch, C.J. Myriad and the Mass Media: The Covering of a Gene Patent Controversy. Genetics in Medicine 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 Controversial Biotechnology Research. Nature Biotechnology 2006;24(11): 13521354.

19. Biotechnology Reference Group, Canadian Council of Churches.

Life: Patent Pending.

20. Gold and Carbone 2010, S54.

21. Joly 2010, 30, 31.

GeNeWatch 27

couNcil for respoNsible GeNetics 5 upland road, Suite 3 Cambridge, mA 02140

GENEWATCH IS FREE ON THE WEB - BUT YOU CAN STILL SUBCRIBE TO RECEIVE PRINT ISSUES. ANNuAl priNT SubSCripTioN rATeS iNDiViDuAl: $35 NoN - proFiT: $50 librAry: $70 CorporATioN: $100

(prooF oF NoN-proFiT STATuS mAy be requireD)

All figures in uS dollars. Future issues of GeneWatch will be exclusively electronic and free at www.councilforresponsiblegenetics.org. if you wish to obtain a special print copy of a single issue, please send a request to the address below or call 617.868.0870. pAymeNT iNFormATioN

please send a subscription request with your full name, address and email address, along with a check or credit card (masterCard or Visa) information, to: Council for responsible Genetics 5 upland road, Suite 3 Cambridge, mA 02140 orders are also accepted online (www.councilforresponsiblegenetics.org) and by phone (617.868.0870) . Additional donations are welcome. Thank you! imporTANT TAx iNFormATioN: THe FAir mArKeT VAlue oF A oNeyeAr SubSCripTioN To GeNeWATCH iS $35.00

support from people like you makes crG’s work possible. much of our income comes from individuals. your support helps keep our programs free of the restrictions that come with funding from pharmaceutical and health care companies or government sources. We are the watchdogs for accurate and unbiased information about biotechnology, even when the truth doesn’t suit current political or commercial agendas. And we depend on you to be able to do what we do.

There are many ways you can help CrG. you can become a donor: an annual gift in quarterly installments of $25, $50 or $100 gives us a wonderful and predictable support with a minimal shock to your budget. you may also be able to designate CrG through your workplace giving program, including the Combined Federal Campaign. many companies will actually match or even double-match your donation. Check with your employer about its matching gift program. you might also consider making an investment in a future where biotechnology is properly used by remembering CrG in your will with a bequest or charitable trust gift.

To learn more about helping CrG, please call us at 617.868.0870. you may also write the Council for responsible Genetics at 5 upland road, Suite 3, Cambridge mA 02140, or visit www.councilforresponsiblegenetics.org.