genewatch vol. 23 no. 5-6

THE MAGAZINE OF THE COUNCIL FOR RESPONSIBLE GENETICS | ADVANCING THE PUBLIC INTEREST IN BIOTECHNOLOGY SINCE 1983

SPECIAL DOUBLE ISSUE

FEATURESGenes, Patents, Common Sense and the Law / James EvansInterviews: The ACLU, Public Patent Foundation, and Myriad Genetics Special topic: Assisted Reproductive TechnologyISSN 0740-9737

VOLUME 23 NUMBER 5-6 OCTOBER-DECEMBER 2010

2 GENEWATCH OCTOBER-DECEMBER 2010

Dedication: Paul Steven MillerJEREMY GRUBER

Genes, Patents, Common Sense and the LawJAMES EVANS

When the Grass Eats the CowsJOHN CONLEY AND DAN VORHAUS

The PlantiffsAN INTERVIEW WITH SANDRA PARK OF THE ACLU

The DefendantsAN INTERVIEW WITH RICHARD MARSH OF MYRIAD

GENETICS

Protecting the Intellectual Foundations ofGenetic Science

EILEEN M. KANE

The Danger of the Broad BrushCHRISTOPHER M. HOLMAN

The Overstated CaseROBERT COOK-DEEGAN

The Sky Is Not FallingAN INTERVIEW WITH DANIEL RAVICHER OF THE PUBLIC

PATENT FOUNDATION

Why Banning Patents Would Hurt PatientsSHARON TERRY

The Physical Embodiment of InformationMAGDALINA GUGUCHEVA

A Return to JudgingMICHELE GOODWIN

Why Genes Must Remain Eligible forPatenting

KEVIN NOONAN

Naturally Occurring Genes and theCommons by Necessity

DAVID KOEPSELL

5

All that glitters is not necessarilypatentable (p. 6)

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It’s time for a rationalapproach to the gene patentmess (p. 8)

Can gene patents coexistwith a preserve of openknowledge? (p 16)

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The President of GeneticAlliance defends the utility ofgene patents (p 24)

The problem with genepatents goes beyond the

practical - it’s also a matterof property rights (p 32)

Special Topic: Gene Patents

Both sides of theBRCA case speak toGeneWatch (p 10and 12)

The Salzberg ScreenAN INTERVIEW WITH STEVEN SALZBERG

In Defense of a Working GoodPAUL BILLINGS

Freedom of GenesDEBRA GREENFIELD

Patents on Genes, Organisms - andHuman(oid)s?STUART NEWMAN

Synthetic Biology: The Next Wave of Patents on Life

ERIC HOFFMAN AND JAYDEE HANSON

****

EEOC Issues Strong Final RuleImplementing GINA

JEREMY GRUBER

Dangerous HarvestDIANE BEESON

Reproductive TraffickingHEDVA EYAL

Film Review: EggsploitationKATHLEEN SLOAN

Topic Updates: DNA Alarms, MandatorySickle Cell Testing, and GM Mosquitoes

Is Government Getting Out of the EthicsBusiness?

JEREMY GRUBER

Endnotes

VOLUME 23 NUMBER 5-6 GENEWATCH 3

36

Despite the legal challenges togene patents, patents onorganisms are still very muchaccepted (p. 38)

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Diane Beeson, Hedva Eyal andKathleen Sloan write on thecritical issues of assistedreproductive technologies (p 42, 45 and 47)

Yes, you are reading this sign correctly (p 48)

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You are reading the largest issue—byfar—in GeneWatch’s 27-year history, andthe majority of the articles and inter-views herein focus on the topic of genepatents. It might have been more diffi-cult to fill the better part of 52 pages withdiscussion of a single topic if everyonewasn’t already talking about it.

Now, you might as well know upfrontthat the Council for ResponsibleGenetics’ official position on genepatents is more than a little critical …which is to say, some of CRG’s board andstaff have put in a good deal of work tosupport a ban of gene patents. However,GeneWatch is not in the business of sim-ply lining up a powwow of agreement.Some of the voices represented in thisissue fall on the other end of the spec-trum, supporting the logic and utility ofallowing patents on genes. DavidKoepsell (p. 32) and Kevin Noonan (p.30) have butted heads over the issue inother venues; James Evans (p. 6) co-authored a key report criticizing the genepatent system, and Paul Billings (p. 35)co-authored the dissent; and Sandra Parkof the ACLU (p. 10) and Daniel Ravicherof the Public Patent Foundation (p. 22)are plaintiffs in the suit against MyriadGenetics, for which Richard Marsh (p.12) is General Counsel.

That case—in which a district courtruled several of Myriad Genetics’ patentson genes related to breast cancerinvalid—is referenced often in the fol-lowing pages. Association for MolecularPathology et al. v US Patent andTrademark Office et al. (or, for short,AMP v. USPTO, or AMP, or ‘the Myriadcase,’ or ‘the BRCA case’) has drawnnational media attention, and with it, thekind of hyperbole made for sound bites.Some opponents of gene patents don’tmind suggesting that by patentinghuman genes, a company or scientist lit-erally owns us; while some pro-patentadvocates seem to believe that thebiotech industry, and the entire country


Editor’s NoteBY SAMUEL ANDERSON

GeneWatch welcomes all commentsand letters to the editor. Please [email protected] if you wouldlike to submit a letter (400 words orless, please) or with any other com-ments or queries.

What do you think?

Sarah Kim is a graduate of Massachusetts College ofArt and Design who enjoys working on any and all kindsof illusration. You can see more of her work atwww.skimilkart.com. This is Sarah’s fifth GeneWatchcover.

Featured artist

GENEWATCH

GENEWATCH is published by the Council for ResponsibleGenetics (CRG), a national, nonprofit, tax-exemptorganization. Founded in 1983, CRG’s mission is to fos-ter public debate on the social, ethical, and environmen-tal implications of new genetic technologies. The viewsexpressed herein do not necessarily represent the viewsof the staff or the CRG Board of Directors.

ADDRESS 5 Upland Road, Suite 3 Cambridge, MA02140 PHONE 617.868.0870 FAX 617.491.5344 NETwww.councilforresponsiblegenetics.org

BOARD OF DIRECTORS

SHELDON KRIMSKY, PhD, Board Chair Tufts University

PETER SHORETT, MPP TreasurerThe Chartis Group

EVAN BALABAN, PhDMcGill University

PAUL BILLINGS, MD, PhD,University of California, Berkeley

SUJATHA BYRAVAN, PhDCentre for Development Finance, India

ROBERT DESALLE, PhDAmerican Museum of Natural History

ROBERT GREEN, MD, MPHBoston University

JEREMY GRUBER, JDCouncil for Responsible Genetics

RAYNA RAPP, PhDNew York University

PATRICIA WILLIAMS, JDColumbia University

EDITORIAL COMMITTEE

Ruth Hubbard Sheldon KrimskyJeremy Gruber

EDITOR & DESIGNER

Samuel Anderson

OCTOBER-DECEMBER 2010 VOLUME 23 NUMBERS 5 & 6

Unless otherwise noted, all material in this publication is protected by copyright bythe Council for Responsible Genetics. All rights reserved. GeneWatch 23,5

0740-973

COVER ART

Sarah Kim

STAFF

Jeremy Gruber, President and Executive DirectorSheila Sinclair, Manager of Operations

Samuel Anderson, Editor of GeneWatchKathleen Sloan, Program Coordinator

Andrew Thibedeau, Senior FellowMagdalina Gugucheva, Fellow

with it, is on its way to utter ruin if genepatents are invalidated.

Yet in a debate so rife with hyperbole,there is a wide gulf of gray area. Even ifthe Myriad case—currently underappeal—must ultimately fall one direc-tion or the other, it has stirred up a widerdiscussion with plenty of room fornuance.

Both the hyperbole and the nuancewere apparent in the various responsesto a Department of Justice amicus briefpertaining to the Myriad case. The briefheld that human genes are, as productsof nature, unpatentable, and that when aDNA molecule is isolated it is “no less aproduct of nature … than are cottonfibers that have been separated from cot-ton seeds or coal that has been extractedfrom the earth.”

Many anti-gene patent advocates cel-ebrated the brief as a victory, eventhough, as Magdalina Gugucheva (p. 26)points out, the brief ’s actual positionactually falls well short of endorsing aban on gene patents. Meanwhile, patentlawyer Harold C. Wegner summed up histhoughts in an email newsletter: “EricHolder Hijacks the Patent System, FlunksPatents 101.”

Exaggeration is interesting, which iswhy I am a bit sorry to tell you that thefollowing pages are chock full of intelli-gent, level-headed discussion. Thenagain, depending on where you stand,you may find some of it not quite soenlightened. At any rate, I can guaranteeyou this much: you won’t agree witheveryone. Wouldn’t that be boring?


This special issue of GeneWatch maga-zine is dedicated to the memory of PaulSteven Miller (1961-2010), who recentlypassed away from cancer at the young age of49. Paul was a friend and advisor to theCouncil for Responsible Genetics, a tirelessadvocate for disability rights and a greathumanitarian. During the course of anextraordinary and highly successful career,Paul fought against those who judge peopleon how they look or their gender, race, age,or nationality.

Paul was born in Flushing, NY with thegenetic condition achondroplasia, a type ofdwarfism. Paul never let his condition definehim or his accomplishments, though. Hewent on to graduate at the top of his class atthe University of Pennsylvania and then Har-vard Law School. Despite his academicachievements, he received 45 rejection let-ters from small-minded law firms beforefinding a position with Manatt Phelps in LosAngeles (Paul's work at the firm wouldbecome the inspiration for the characterHamilton Schuyler on the series L.A. Law).

Paul went on to become Director of Lit-igation for the Western Law Center forDisability Rights, a leader of Little People ofAmerica, and then Deputy Director of theU.S. Office of Consumer Affairs. An appoint-ment as White House liaison to the disabilitycommunity followed, a position Paul heldunder both the Clinton and Obama admin-istrations, and which he used to help recruitindividuals with disabilities to take positionsall over both administrations. "I felt com-pelled to do something more meaningfulwith my career that would have an impact,"he said in a 2004 interview.

And have an impact he did. Paul wasinstrumental in helping write the Americanswith Disabilities Act, the landmark civilrights law which marked its 20th anniversaryseveral months ago. In his own words:

I think the reality for students with dis-abilities, for professionals withdisabilities, is dramatically differenttoday than it was a scant 15,18 years ago… I think that's attributable to the ADA,to an education process that employershave begun to journey down … It hasmade America stronger, because it forcesemployers to focus more on people'squalifications than on stereotypes aboutthat individual's disability.

In 1994 President Clinton appointed

Paul to be a commissioner of the EqualEmployment Opportunity Commissionwhere he worked for ten years, becomingone of the longest serving Commissioners inthe history of the Commission. As Commis-sioner, Paul spent much of his time ondeveloping ADA enforcement. He success-fully spearheaded efforts to improve theagency's legendary backlog through media-tion and became the agency's most visiblespokesperson against all types of discrimi-nation, particularly on behalf of people withdisabilities, reaching out to people all overthe United States and the world, educatingthem, encouraging them to use the system,and as a result improving the lives of mil-lions.

Paul was a member of the HHS Secre-tary's Advisory Committee on Genetics,Health and Society. Noting gaps in the ADA,Paul became an early champion of geneticnondiscrimination legislation and frequentlywrote on the topic. It was in this vein that Icame to know Paul as we worked togetherfor over 15 years on the successful passageof what would become the Genetic Informa-tion Nondiscrimination Act. Paul was a truegenius on disability and employment dis-crimination law and a force of nature onany issue he worked on. He helped settle theEEOC's first court action against genetictesting in the workplace and led the draftingof the Presidential Executive Order onGenetic Discrimination and Privacy whichcreated the first legal protections againstgenetic discrimination for Federal employ-ees. That same year, in testimony before theU.S. Senate, Paul declared:

In this country, people should bejudged based upon their abilities, and notbased upon fears, myths, or stereotypes.Yet, with the expansion of genetic infor-mation available to employers, there isa risk that employers will misinterpretand misuse genetic test results to weedout persons according to their perceivedhealth risks based on genetic informa-tion. Furthermore, people may refuseto take genetic tests, a potentially life-saving measure, out of fear that employ-ers may discriminate against them. Forthese reasons, genetic information doesnot belong in the workplace.

Paul left the EEOC in 2004 to become theHenry M. Jackson Professor of Law at theUniversity of Washington School of Law

from which he took a temporary leave toserve as Special Assistant to the President inthe first year of the Obama administrationwhere he managed Presidential appoint-ments and nominations. In his final years hefocused on tensions between disability rightsand genetic science. In a paper titled "Avoid-ing Genetic Genocide," Paul criticizedscientists for what he saw as their eagernessto use genetics to produce "perfect" humans.He wrote:

Good health is not the absence of a dis-ability. Scientists caught up in theexcitement of genetic discovery can for-get that life with a disability can still bea rich and fulfilling life.

As his wife, Jenni, recounted at his recentmemorial service in Washington D.C., Paulhad the "golden rolodex." But unlike mostwell connected persons, Paul built friend-ships from the most distinguished ofcolleagues to the least and everyone inbetween. Moreover he went out of his wayto give of his time to everyone he knew. Andhe did it all with an incredible wit and senseof humor. In his final year, when cancer treat-ments required his arm to be amputated,Paul joked that he was the only one-armedJewish dwarf to ever serve in the WhiteHouse.

In a statement released shortly after hispassing, President Obama declared aboutPaul Miller:

More important than any title or posi-tion was the work that drove him. Hededicated his life to a world more fair andmore equal, and an America where all arefree to pursue their full measure of hap-piness, and all of us are better off for it.

Paul was a giant to everyone who knewhim and he will be sorely missed. Our bestwishes go out to his wife Jenni and daugh-ters Naomi and Delia.

Jeremy Gruber is President and ExecutiveDirector of CRG.

Dedication: Paul Steven MillerBY JEREMY GRUBER

The Secretary's Advisory Commit-tee on Genetics, Health, and Society nolonger exists, having been allowed to sun-set in late 2010. The committee was activeon many fronts, having weighed in on theissue of genetic discrimination, direct toconsumer genetic testing, and the regu-lation of laboratory testing, among others.One of its most high profile legacies maybe the work that it did with regard to genepatenting.

In early 2010 SACGHS made a set offormal recommendations to the Secretaryof Health and Human Services advocat-ing that legislative actions be pursued tocreate an exemption from infringementfor those who use patented genes in diag-nostic tests as well as to create a broadresearch exemption for those who usepatented genes in the pursuit of research.The report also advocated against thegranting and enforcement of "associationpatents" in which a simple association

between genotype and phenotype isclaimed as patentable. The recommenda-tions of SACGHS were lauded by someand reviled by others.

In light of events since issuance of thatreport, the recommendations may seemless extreme to those who objected tothem. Notably, in the spring of 2010,Judge Roberts Sweet issued a ruling in theFederal District Court for the SouthernDistrict of New York which, while tangi-bly of minimal effect, served todramatically focus attention on the issueof gene patents and make a high profilecourt case even more dramatic (Associa-tion for Molecular Pathology et al. v. USPatent and Trademark Office et al.). Inshort, Judge Sweet ruled in summaryjudgment that the plaintiffs were correctand that genes were not legitimatelypatentable material. His argument wasnovel and, at least to this geneticist, per-suasive. In short, Judge Sweet argued that

the natural function of a gene is to encodeinformation and thus the mere isolationof a gene (or for that matter its manipu-lation into another form which does notsubstantially affect the nature of thatinformation) does not qualitativelychange the material in any legitimateintrinsic sense and therefore cannot bepatented.

The next surprising development wasthe filing of an amicus brief by theDepartment of Justice which arguedlargely in support of the plaintiffs, agree-ing that naturally occurring genes are notpatentable material. The case is beingappealed, and while conventional wisdomholds that Judge Sweet's decision will beoverturned, if there is one thing we shouldhave learned from the recent history ofgene patents and the courts it is that mak-ing predictions is a rather hazardousendeavor.

Taking the (perhaps naïve) view thatlogic should play a role in the decisions ofcourts, it seems to me that the way for-ward is clear. The information contentof any given gene has evolved over mil-lions of years and human genes existedwithin us long before we began to dis-sect our own genomes. Patenting theinformation contained in human genes(by either patenting a naturally occurringgene or a modified version of that genewhich imparts essentially the same infor-mation) is extremely hard to justify whilemaintaining a straight face. The law hasalways held that we cannot patent gold,sunshine or an unmodified field mouse.It is therefore difficult to envision justhow we could legitimately sanction thepatenting of naturally occurring genesor the information contained therein.One is, of course, perfectly free to patentnovel and inventive methods for purify-ing an element like gold or silver, as wellas new means of capturing sunlight toaccomplish a particular purpose like pow-ering an electrical grid. One is also free topatent a new type of mouse that has neverexisted before. In the same vein, if onemodifies the information in a gene in a


Genes, Patents, Common Sense and the LawEliminating patents on naturally occurring phenomena is both logical and in our best interest

BY JAMES EVANS

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way that is novel, non-obvious, and use-ful, it is eminently reasonable to expectpatent protection on such an invention.The creation of new DNA sequences thatperform novel feats and convey novelinformation should be patentable–butmerely isolating a naturally occurringgene and distilling its information (forexample in a cDNA), no matter how dif-ficult, ingenious or useful, renders thatgene no more patentable than silverwould be should I invent a new methodfor its purification.

In the furor over gene patents it isoften forgotten just why the patent sys-tem exists in the first place. Patents wereenshrined in the US Constitution in orderto "promote the progress of science anduseful arts." Thus the primary intent ofthe patent system is a broad socialgoal–not the creation of profit. Certainlythe harnessing of self interest is a signif-icant means by which the patent systemexerts its power, but we should not forgetthat stimulation of commerce is only themeans by which we hope to achieve thebeneficial effects of the patenting system.If the primary intent of the patent systemwas merely the stimulation of commercethen we would, as the DOJ brief pointed

out, allow the patenting of far more thingsthan we do.

The hyperbole found on both sidesof this debate can reach remarkable lev-els. On one hand, I see no inherentmetaphysical objection of the patentingof genes or life forms as long as they aretruly novel, useful and non-obvious.Indeed, should human ingenuity proveable to best evolution by creating novelDNA sequences which impart new infor-mation in order to treat disease and easehuman suffering, this seems a worthy(and patentable) pursuit. On the otherhand, patenting is not a right. It is a priv-ilege granted when certain specific

conditions are met–conditions whichhave not been met by those who hold cur-rent gene patents.

Moreover, the claims that the com-mercial scientific infrastructure of thecountry will topple if gene patents arefound to be unenforceable are silly.Indeed, the evidence suggests that farfrom precipitating catastrophe, the elim-ination of gene patents would be a boonto commercial activity. The SACGHSreport, based on empiric studies of the

gene patenting landscape, is particularlyinformative with regard to this issue.About 20% of the human genome ispatented, which means that some dis-ease-relevant genes are under patentwhile some are unconstrained by exclu-sivity. In work commissioned bySACGHS, a study of this landscaperevealed that for genes which happen notto be under exclusive constraint (such ascystic fibrosis and Huntington's disease)a thriving market place exists wheredozens of laboratories –both private andpublic–vie to outcompete one another onthe basis of innovation, quality and serv-ice. However, for those genes controlled

by patent-enabled exclusivity, where onlya single laboratory is permitted to analyzethem, what one sees is a striking lack ofany meaningful competition, undermin-ing access, quality and innovation. To besure, those few companies that havestaked their business model on insuringno competition through the enforcementof gene patents will suffer should genesbe rendered unpatentable–but both thebroad market and the public will bene-fit.

Finally, the SACGHS report advo-cated that a broad exemption be made forthose who use patented genes in the pur-suit of research. Nothing could be morein keeping with the intent of the patentsystem itself. Indeed, restricting researchwith patents is antithetical to the verypurpose of the patent system: instead ofpromoting progress, it squelches progressand innovation at the most proximal con-ceivable point.

Thoughtfully granted patents are anundeniable boon to progress and humanwell being, but inappropriately grantedpatents can just as surely suffocate inno-vation. Eliminating patents on naturallyoccurring phenomenon such as the infor-mation contained in genes is not onlylogical but will stimulate progress andproductivity. The elimination of toll gatesat the extreme upstream position of thegene will harness self interest and humaningenuity to the benefit of all.

James P. Evans, PhD, MD, directs theClinical Cancer Genetics Services at theUniversity of North Carolina School ofMedicine and was a member of the Sec-retary's Advisory Committee on Genetics,Health, and Society.


Those few companies that have staked their business modelon insuring no competition through the enforcement ofgene patents will suffer should genes be renderedunpatentable ... but both the broad market and the publicwill benefit.

and the single court decision to considerit even obliquely–the Federal Circuit's1991 decision in Amgen v. Chugai–haddismissed it in a footnote. Chemistry tri-umphed over information, and thesemantics of patent claiming seemed tohave foreclosed a potentially fundamen-tal issue.

Then came Judge Sweet's Myriad(Association for Molecular Pathology v.USPTO) district court opinion invali-dating Myriad's isolated gene patents and,at least for a moment, the world turnedupside down (the title of the song thatCornwallis' band played during the sur-render at Yorktown: "If ponies rode menand if grass ate the cows"). Judge Sweetadopted the information-first argument,deriding the gene-in-isolation distinctionas "a patent lawyer's trick." Roberte andI were simultaneously gratified and hor-rified that our thought experiment hadbecome (at least ephemeral) legal real-ity.

As we await the Federal Circuit's deci-sion in Myriad, there's very little new tosay about the case. Reactions have been

predictable. Disinterested legal commen-tators have almost universally predictedthat the Federal Circuit will reverse or atleast significantly limit the scope of thedistrict court's ruling–it's just too doctri-nally radical to stand, posing too muchrisk to the biotechnology industry. Advo-cates have performed their expectedroles: Big Biotech sees signs of the apoc-alypse, while public domain enthusiastssee a new golden age of genetic researchunencumbered by patents.

Most of this attention, however, hasbeen focused on what might be the lessimportant part of the case: the genepatents. Technology and other principlesof patent law may be conspiring to reducethe practical significance of single-genepatents. On the technology side, moreefficient (and much cheaper) whole-genome sequencing may permit newapplications to avoid "using" protectedsingle genes in isolation. (The Patent Actprohibits making, using, or selling thepatented invention exactly as it's claimedin the patent.) Nonetheless, at least in theshort to medium term, single-gene


Back in 2003, patent lawyer RoberteMakowski and I published an article inthe Journal of the Patent & TrademarkOffice Society in which we argued that lit-igants and courts should revisit whetherpatents on genes, as conventionallydrafted, violated the prohibition onpatenting products of nature. We notedthat claims on "isolated" (removed fromtheir natural environment in the body) or"purified" (often, with non-coding regionsremoved, as with cDNA) genes evadedthis prohibition by putting the focusentirely on chemical differences betweensuch genes and their naturally occurringprecursors. We then asked whether thisexclusive focus made sense, given thatpeople are interested in patenting genesbecause of their information-carryingcapacity, which is the same in the natu-ral and patented versions. We also notedthat neither the United States PatentOffice nor the courts had ever squarelyaddressed the product of nature argu-ment. The USPTO had brushed it asidewith references to novelty and utility,which are separate statutory questions,

When the Grass Eats the CowsThe gene patent mess calls for a rational solution

BY JOHN CONLEY AND DANVORHAUS

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patents are likely to impede the develop-ment of gene-based diagnostictechniques (especially "multiplex" tech-niques that use multiple genes).

On the legal front, note that Myriad isabout only one aspect of patentability:whether the claimed invention ispatentable subject matter. To say, as JudgeSweet did, that an isolated gene is a prod-uct of nature is to say that it does not fallwithin the realm of patentable subject

matter. But in a 2009 case called In reKubin, the Federal Circuit made it mucheasier to defeat single-gene patents onobviousness ground. Reversing its own1995 precedent, the court held that a gene(in cDNA form) was obvious when a lotwas known about the protein it encodesand the method for sequencing it was alsowell-known-in other words, when it was"obvious to try" to sequence that gene.This reinterpreted obviousness require-ment may prove to be an insurmountablebarrier to many, if not most, single-genepatents in the future.

The less-discussed but potentiallymore significant patents at issue in Myr-iad are the company's method patents.These cover methods of making sense ofgene test results and using them to makediagnostic predictions. They are extraor-dinarily broad, allowing Myriad tomonopolize just about any diagnostic useof the breast cancer genes, regardless ofthe patents on the genes themselves.

The patentable subject matter status

of methods generally is up in the air. TheSupreme Court had a chance to clarifythings this past summer in Bilski v. Kap-pos, which involved a simple businessmethod, but its fractured opinions onlyconfused things further. All we know forsure is that the Federal Circuit's machine-or-transformation test (which requiresthat a method be tied to a particularmachine, or transform something into adifferent state) cannot be the sole test. We

await the Federal Circuit's fur-ther (remand) decision inBilski, as well in Prometheus v.Mayo, which involves anothersimple method, this time foradjusting the dose of medica-tion after measuring its level inthe body. The Federal Circuit'sdecision in these two cases(assuming they come first) willpresumably shed some light onthe likely fate of the Myriad

method claims, and on medical associa-tion and diagnostic patents moregenerally.

Amidst all this legal uncertainty, it isworth stepping back and taking a practi-cal look at the whole situation. Both setsof extreme reactions to Judge Sweet'sMyriad decision are almost certainlywrong: it is not the end of the world forcommercial biotechnology, nor is it thebest possible outcome for science andmedicine and their constituents-that is,us. Gene patents themselves are not evil.On the contrary, they–and their prom-ise of monopoly rents–have played anessential role in financing the biotechnol-ogy industry. The problem is not withgene patents per se, but with the way thatthey can be used as barriers to researchand innovation. If Myriad had made dif-ferent business judgments, its patentswould probably not be under attack.Would the ACLU have targeted Myriadif, for example, it permitted second-opin-ion testing by independent labs at

patient-friendly prices? Or if it hadannounced a broad, royalty-free researchlicense for its genes?

The complexity of the gene patentlandscape–keep in mind that there arepatents on an estimated 20% of humangenes–along with the actions of certainpatent holders, including Myriad, havecombined to produce a dense gene patent"thicket" that threatens biotechnologyinnovation, particularly in the area ofmultiplex diagnostic technologies. Thepublic disaffection with gene patents thatJudge Sweet's opinion expresses so clearlywill only get worse if the gene patentthicket begins to materially impair thedevelopment of these technologies. It'stime for the biotechnology to movetoward the kind of patent pooling that hasfacilitated the advance of so many othertechnologies, from sewing machines tojet engines. Innovators should have aplace for one-stop shopping at reasonableprices, rather than facing individualpatent-holders bent on monopolizationand stacked gene patent royalties thatthreaten to exceed 100% of their rev-enues. Some biotech players might haveshort-term reasons for opposing thisapproach, but the current legal messought to be a wake-up call: if the indus-try doesn't move in this direction of arational economic solution, courts andlegislators will likely impose somethingfar worse.

John M. Conley, PhD, JD, University ofNorth Carolina School of Law; Of Coun-sel, Robinson, Bradshaw & Hinson,Charlotte, NC; Contributor, GenomicsLaw Report.

Dan Vorhaus, JD, Robinson, Bradshaw &Hinson, Editor of Genomics Law Report.


Both sets of extreme reactions toJudge Sweet’s Myriad decision arealmost certainly wrong: it is not theend of the world for commercialbiotechnology, nor is it the best possible outcome for science andmedicine and their constituents.

The Council for Responsible Genetics has launched anew blog: Genetic Watchdog. Watch for regular newsand commentary as recorded by CRG staff, board mem-bers, and friends, and join the discussion by leavingyour own comments. You don’t have to wait for the nextGeneWatch to keep up with the latest events in biotechnology and ethics!

The blog can be found at: http://www.councilforresponsiblegenetics.org/Blog.

Sandra Park, JD, is an attorney at theACLU Women’s Rights Project.

Was the gene patents suit somethingthat has been in the works for quite awhile, or was it Myriad's more recentbehavior that really spurred it?

The case was developed over a signif-icant period of time, but by the time it wastaking shape, Myriad had already ownedits patents for a long time, so we knew howthey were enforcing their patents. Whenthey obtained their patents, they immedi-ately sent out cease and desist letters tolabs, including a lab right by two of ourclients. They immediately took action toenforce their patents in such a way as toprevent other labs from conducting clin-ical testing.

Have you seen differences in the waythat people are viewing gene patentssince beginning work on this case?

When patents on genes were firstbeing issued back in the 1990s, there wasadvocacy organized to try to oppose thosepatents at the time, and it came largelyfrom the scientific community and alliedgroups. At the time, though, I don't thinkthat there were legal arguments for whythese sorts of patents were invalid, and Ithink the case has really brought thoselegal issues-that these patents are for prod-ucts of nature and therefore should nothave been granted in the first place-to thefore. With the lawsuit and the accompa-nying media attention, there certainly hasbeen greater awareness about the fact thatgenes are being patented. I think that thescientists who have been concerned aboutgene patents were on some level not surehow to do any further advocacy on theissue, and I'd say that there wasn't reallythat much advocacy being done on theissue until the lawsuit came around. Therehas been a lot of renewed interest in try-ing to stop these patents from interferingwith clinical practice and research.

Do you see that activism still gainingmomentum, even after the initial explo-sion of media coverage around theDistrict Court's ruling?

Well, media coverage tends to focus on

specific events, so when the court decisioncame out, there was a lot of attention-par-tially because those in the patent worldand in biotech were very surprised by thedecision. But I wouldn't say the advocacyhas died down, and I think that as the casecontinues through the appellate process,the media will be following it closely. Theeducation that needs to be done on thisissue should not just focus on the case.Whatever happens with the case-and Itotally expect it to be successful-there areother fronts where people should continueto confront this issue.

You know, media ebbs and flows, andthe case has been a galvanizing force formedia attention thus far, but other advo-cacy efforts are being organized. Therewas the SACGHS report which did getsome media attention when it came out inFebruary, making recommendations asto why gene patents should not beenforced, and in Australia there has beena lot of attention on the issue more gen-erally and there have been ongoingadvocacy efforts, both through a govern-mental investigation and a lawsuit that wasbrought there. So aside from this case,it's an issue that continues to receive a lotof attention.

What kind of patterns do you see, if any,in terms of who lines up for and againstgene patents?

The plaintiffs in the case are scientificorganizations, physicians, geneticists,researchers, patients, and breast cancerand women's health advocacy organiza-tions; and I think that the amici and ourside have really represented the entiremedical and scientific community. Wehave also had some expert declarations,most notably from Joseph Stiglitz, on theeconomics of patents and why a patentincentive is not necessary and in factimpedes both economic progress and sci-entific progress on these issues.

On the other side it has been, for themost part, biotech–but a particular seg-ment of biotech. I think part of the reasonis that these patents have been issued bythe Patent Office for a period of time, andso, from an industry perspective, there'sa level of comfort with the status quo,

regardless of the merits of the issue. Ourposition has always been that we actuallythink these patents impede the kind ofresearch that I think a lot of biotech com-panies want to do in terms of developmentof products, and there are new technolo-gies that are being developed that willactually be impeded if you need to go outand get licenses and permissions frompatent holders on genes. My take on it isreally that those who have come outagainst the suit are either patent holdersthemselves or part of the industry, and arejust more comfortable with the status quo;but that in fact, if these patents were lifted,it would actually help their industrybecause there would no longer be imped-iments to the kind of research and productdevelopment that they want to do.

If the plaintiffs win this case, how closedoes it come to closing the book on theissue? Will there still be a need to drawattention to gene patents?

If the case is successful, it will be set-ting precedent for many, many genepatents; so while the case is being broughtagainst particular patents, a ruling findingthat isolated DNA cannot be patented willaffect the other gene patents that are outthere. I don't think public education onthis issue should be focused on the case somuch as on the fact that the Patent Officehas been issuing these sorts of patents, andreally looking, policy-wise, at why thesepatents don't serve our health and sci-ence policy. I think the case has been agalvanizing point in terms of how to bringthis issue to the public and to the media,but I'd like the discussion to be muchbroader than simply the legal argumentsthat are being made.

Are there any specific misconceptionsyou hear repeated a lot, other than justlegal arguments, that you would like to


The PlaintiffsAn interview with Sandra Park of the ACLU

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ongoing problem. We have learned whatthe problems are from years of thesepatents being put in place and beingenforced. Because we have had those badexperiences, seeing how these patentsaffect clinical practice and patient care, ithas become even more clear to us thatthese patents should be challenged.

While working on this issue, I've noticedthat certain people on either side of thedebate seem to think that no reasonableperson could agree with their oppo-nents. So: is there any argument in favorof gene patents where you think reason-able people could disagree?

I understand why patent holders wantto protect these patents, but I really haven'tseen the arguments to back it up. Thething that I've heard most, and that Myr-iad has said most in their papers, is thatthey had to have the patent protection inorder to commercialize the patents andspend many millions of dollars advertis-ing the product and educating doctorsabout the test. I do think it's important forthat kind of education to happen, so I cer-tainly agree that it's an important functionthey have played; but I don't think at allthat a patent is necessary for that to hap-pen. Really, that has been the main

argument that I have heard, and a lot ofthe research that has been done on thatissue show that patents are not at all nec-essary in terms of creating genetic tests.

Other than that, the legal argumentshave really not been compelling at all tome. It is true that each side sees it in theirown way, but what I have found most strik-

ing is that the other side really does notwant to acknowledge that the SupremeCourt has recognized limits on what ispatentable subject matter, regardless ofwhether it is new or useful. There are stilllimits to what can be patented, even if youare identifying something for the first timeor even if you are identifying somethinguseful. When Einstein gave us E=mc2, itwas new and useful, but it could not bepatented. That's what has been most strik-ing to me, the rejection of that legalprinciple.


clear up?One argument we've heard is that this

case will be the downfall of the biotechindustry, and I just don't think that's at allthe case. Our goal here is really to lift themonopoly on genes, the central thingneeded for research and development tooccur, so that's one of the spins on the caseI think is wrong.

In terms of public perception, whenpeople first hear about it, I think theirimmediate assumption is that we're talk-ing about patents on genetic tests, so we'vereally tried to make clear to people that thepatents here are on DNA itself and noton particular tests. The way I think thatis made especially clear is the fact thatwhen Myriad obtained its patents on theDNA, they were able to send cease anddesist letters to labs that were using differ-ent tests than the ones that Myriad uses.It is because their patents are on the actualDNA that they were able to stop labs fromusing different testing methods to analyzethose particular genes.

The other thing is just letting peopleknow that this isn't a new issue–the scien-tific community has been concerned aboutit for a long time. It's new in the sensethat this is the first lawsuit that has beenbrought to challenge it, but it's been an

This isn’t a new issue–thescientific community has

been concerned about it fora long time.

Richard Marsh, JD, is Executive Vice Pres-ident, General Counsel and Secretary ofMyriad Genetics.

The Department of Justice recentlyreleased a friend-of-the-court briefagreeing with Myriad on some points,but holding that isolated DNA mole-cules are a product of nature andtherefore not patentable. Would youcount yourself among the many peoplewho were surprised by this position?

Yes, absolutely we were surprised. Par-ticularly when you look at the past 30 yearsof practice of both the courts and thePatent and Trademark Office, which hasnow issued literally thousands and thou-sands of isolated DNA patents for human,plant and animal application … to see thisshift now was very surprising. A curiousnote is that David Kappos, the director ofthe Patent and Trademark Office has saidthat at the PTO, they're continuing busi-ness as usual, that they're not following theposition of the Department of Justice.

Did you get the sense that the PTO hadnot exactly signed onto this position?

Clearly, as far as the brief, they did notsign on, they did not participate. The bestthat we can tell at this point is that the PTOdoes not agree with this position. I thinkwhat we find kind of curious–but maybenot too surprising, given the currentadministration and the things they havebeen trying to implement–is that here youhave the PTO, 30 years of practice, and tenyears they've had these guidelines whichwere put in place after public notice, pub-lic hearings, public comments; and nowyou have this shift in position which wasdone overnight, behind closed doors, withno public comment and no notice, whichruns against 30 years of established indus-try practice.

The other thing which is troubling isrecognizing that all we have because of thebirth and growth of the biotech industry,which is now $30 billion in R&D spent in2008 alone … a tremendous industry hassprung up, all of which is now in jeopardy;that in today's economic times, when we'retrying to find jobs and stimulate the econ-omy, the current administration wouldtake a position which will result in a loss of

jobs and revenue. To take a position againstall of that is rather surprising and trou-bling.

That's one of the common arguments infavor of gene patenting, that they incen-tivize capital investment to fundresearch; but there are also plenty ofpeople who argue that gene patentsactually inhibit research. Is there any-thing you can point to that convincesyou that gene patents incentivize ratherthan stifle research?

I would absolutely refute those allega-tions. They were postured in the lawsuit totry to influence Judge Sweet's decisionmaking. As to Myriad specifically, they'reabsolutely false. How can you say that Myr-iad has ever, just once, told anyone not todo research? Not once. In fact there havebeen over seven or eight thousand arti-cles which have been published on theBRCA1 and BRCA2 genes. Over 18,000different authors have been researchingthis. It's just mind boggling to think thatanyone would make that premise. As to theBRCA patent, specifically, it's just not sup-ported by the record whatsoever. And it'svery curious … you'll notice that halfwayinto the litigation, once Myriad profferedall the proof and showed how widespreadthis has been researched and published,the ACLU attorneys started changing theirposture and saying, "Well, patents do giveyou the right to prohibit research." Andthey're right, they technically do, butnobody so utilizes them.

One of the best things you can do is toread the amicus brief filed by Chris Hol-man and Robert Cook-Deegan. It wasn'tfiled in support of a specific party, but itdoes contain a very appropriate listing ofvarious reports that were done, all of whichconcluded that there was no evidence thatpatents hinder research, that patents driveprices up or result in more expensive test-ing. It's easy for me to say all of thesethings–I do have a biased opinion–but ifyou go look at that evidence, put forth bya third party unaffiliated with Myriad whofelt it was so important that they took thetime to address that of all of these per-ceived evils, none of this is taking place.There's no evidence to suggest that thesethings actually happened.

Does that mean you would support a lawor precedent that would continue toallow patents on isolated DNA mole-cules but would prevent patent holdersfrom prohibiting research on thosegenes?

Myriad would have no problem withthat position. In fact, there are a fewinstances in which Congress has alreadysaid that you cannot enforce a certainpatent against medical practitioners if it'snecessary in connection with human treat-ments. Congress clearly can do that, andwe'd be fine with it. If you think about it,for practical purposes, for a diagnosticcompany, you need research done. Whenwe first developed the BRCA test, none ofthe doctors would do the testing. The med-ical societies which dictate the guidelinesabout what doctors should and should notdo–the American Congress of Obstetri-cians and Gynecologists, the AmericanSociety of Clinical Oncology–we neededthem to publish guidelines to advise doc-tors to recommend our tests. The only wayguidelines get published is if people doresearch and talk about this, so we're outthere paying people and giving them sam-ples, telling them to do more research. Inthe health care industry, the last thing anymedical diagnostic provider would do istell someone "don't do that research."

So that certainly would be a very appro-priate suggestion, and I think some peoplehave suggested it before, that there oughtto be a research exemption. We would sup-port that.

So if research isn't a threat, when doesMyriad have the motivation to enforcepatents? There must be some situationswhen these patents need to be enforced-that's why they're important, right?

Well, it's difficult to say. There has beena lot of use of the patents out there in theworld. The only two instances when we'vedone anything were ten years ago, when


The DefendantsAn interview with Richard Marsh of Myriad Genetics

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two professors at a University of Pennsyl-vania lab started doing commercial leveltesting. Our belief back then was that wehave spent all this time and effort, we werespending hundreds of millions of dollarsto make the investment to commercializethe test and have a gold standard test, andthat was an instance where we thought itwas inappropriate for them to ride ourcoattails, if you will. We had raised thatissue with them, and the University askedthem to stop doing the testing.

Since then, you've raised a good ques-tion: When will we enforce the patents?Well, I would like to think that Myriad hasnow become the gold standard, andbecause of the quality and turnaround timeof our tests, that's why people come to us.There hasn't been a need to enforce thepatents, just because, I think, people havecome to seek us out not just because of ourpatents, but more so because of the qual-ity of the test we're providing.

If that's the case-that it's less about thepatents on the specific gene than thequality of the actual diagnostic test-whynot tell the Penn professors, "You can'tuse the same test that we do, but you cancome up with some other test that stillinvolves the BRCA gene?"

If you think about it, this is the bedrockof the patent system: In exchange for thislimited period of exclusivity, you arerequired to disclose your invention, talkabout your discovery, and indicate how itcan be practiced, in order to spur innova-tion, so people can design around it.

People can come up with alternativemanners and mechanisms by which theycan come up with a predictive test. That allwould be outside the scope of our patent,we would not have the ability to prohibitthat. That's why it spurs innovation: if youmake disclosures, others can designaround it and improve upon it.

The problem is that, if patent protec-tion not in place, the original incentive tospend the dollars and effort to make the

inventions doesn't happen. Secondly,instead of disclosing inventions, they arekept as trade secrets and not disclosed, sopeople don't learn about the advancementsin science.

Although it seems like if you had a secretway of coming up with a diagnostic test,people would be pretty reluctant to buythe test if they don't know how theresults are being determined.

So you have to explain it to the medicalsociety, you have to show why your genepanel test really will be predictive of theoutcome. That's my point: Myriad, forexample, never would have spent the over$500 million we now have spent-it tookus over ten years to even recoup our invest-ment-but we did it because we knew wehad patent protection. If we didn't havethat, we would not have spent the money.This is why I say that without gene patents,we would have less innovation, we would

have less personalized medicine testingcoming on the market, because peoplewould just not spend the money to developit.

Does Myriad conduct any research orcommercialize any products using geneson which it does not own the patents-or,for that matter, genes which have beenpatented by somebody else?

No, we don't. We now have eight dif-ferent molecular diagnostic products. Halfof them are predictive medicine, wherewe'll look at genes and try to determine ifthere are mutations; some of them are per-sonalized medicine, where we'll try todecide, based on biomarkers in the body,whether someone is getting an effectivedose of a drug. But every time we look ata test, one of the first questions we ask is:What is the intellectual property positionon this? Can we get a license to it? Forinstance, some of the work for a pancreatictest we're doing was developed at JohnsHopkins, and we got a license from themto go ahead and do this test. We will not doa product unless we know there's intellec-tual property protection, because we knowit will take years to publish it, to teach doc-tors about it, and we're not going to do all

that work just to have someone come inbehind us and start doing the same test.

Couldn't it actually benefit Myriad insome projects not to have to deal withintellectual property issues?

The investment just wouldn't happen,because there's no guarantee that we'll beable to get a return on our investment. Thelast company I worked for wasIomega–remember, they made zipdrives–but this is not like that, a productwhich you can just develop and immedi-ately put it on the market place. You haveto validate it, you have to prove that thegene panel works. We're looking a lot morelike a pharmaceutical product in the reg-ulatory approval that takes place. Nobodywill spend the three to five years of devel-opment if there's no patent protection.Look at the pharmaceuticals: they won'tlaunch a product unless there's patent pro-tection to do it.

But how much of all that money is reallyinvolved in locating and isolating thegene, as opposed to the cost of actualcommercialization?

That's a very important question. Ithink lots of people get lost in this idea thatthe gene would have been discovered any-way. That's absolutely right. But with thediscovery of the gene, you're just gettingout of the starting block. In 1996, when welaunched our test, if you took a femalepatient who walked into some OBGYNclinic and said, "Hey doctor, I'm concernedabout my family breast cancer history," thedoctor would just give them a mammo-gram. Nobody knew about cancerpredisposition risk, and this is what we'vebeen doing, taking the time to help spon-sor research and educate medical societiesand the insurance industry.

And who does that? You've got to havea company, you've got to have a medicaldepartment, an accounting department, alegal department … I mean, we're a 1,000employee company. The discovery alonejust barely starts the process. It's discoveryplus commercialization that actually ben-efits society.


I think lots of people get lost in this idea that the gene wouldhave been discovered anyway. That’s absolutely right. Butwith the discovery of the gene, you’re just getting out of thestarting block.

lions and millions of dollars when this isnot an issue? You're free to practice it, thepatent is not being enforced." So, to try tounderscore that point, we said, "Look, we'lleven surrender the actual patent, becauseit makes no difference." Right now we'restill in the process of telling them it's non-sensical–why are we having litigation overpatents that aren't being enforced? Go findsomeone who is enforcing patents if youwant a real live case.

That's the only reason we offered tosurrender the patent-because it wasn'tbeing enforced.

And do you know whether that licenseein Australia, Genetic Technologies, isgetting by financially without the BRCApatent?

I don't know much about that. They'renot like Myriad, where it's a substantialpart of our business. They do a variety ofother types of testing, so for them theBRCA analysis testing is not a main prod-uct.

Is that difference the reason it's worth-while for Myriad to spend millions inlegal fees for the case in the U.S. insteadof just surrendering the patent and rely-ing on the quality of its testing?

Let me give a little color to that … thiscase is not about Myriad. They only sued

us on 15 claims of sevenpatents, and we have 23patents that cover BRCAanalysis. If we were to lose all15 claims, we'd still have all23 patents. Patents don't justgo away because you lose aclaim here or a claim there.

This lawsuit will not have an impact onMyriad. Our intellectual property positionwill remain strong. It's going to have amuch greater impact on the biotechnologyindustry as a whole. Actually, it did crossour minds: Why even bother to appealthis? It's just Judge Sweet, it's not a bind-ing decision, this case is not impactful onMyriad … why spend all the money and theeffort? And the reason is, this is an impor-tant issue to the biotechnology sector. Weclearly believe that the patent systemworks. We believe we are a poster child ofthe success of how public science has beenpromoted because of the patents grantedon the genes. We firmly believe that soci-ety as a whole has benefited. I clearlyappreciate that there will always be a fewanecdotal stories, there will always be ahandful of individuals who because of theirpersonal circumstances may be negatively

affected. I don't want to minimize that-it isa real issue for someone who has a familyhistory and can't afford the test. Myriadspecifically provides free testing for thosewho fall below a certain welfare level.

Having said that, if you take society asa whole, clearly society has been benefitedby the patenting of the BRCA genes and allthe biotech patents out there. Look at allthe personalized medicine products outthere today. And remember, in a few shortyears our patent is going to expire, and thisbenefit goes back to the public as a whole.

If losing this case isn't going to have a bigimpact on Myriad in terms of business,are you saying that Myriad is footing thebill on behalf of the entire biotech indus-try?

We clearly are being forced to respondto this lawsuit. We would love it if theACLU would find someone else who isenforcing their patents against people.We'd be happy if they would go find somecompany that has a patent on toe fungus.But obviously they picked Myriad becausewe have the breast cancer gene, becausewomen's health is a very high profile andemotional area. Let's all recognize whatthis is–that's the only reason they pickedus. It's not necessarily because we have iso-lated DNA–there are tens of thousands ofisolated DNAs out there, so why didn't theygo pick on DuPont or Monsanto or Eli Lillyor anyone else? They picked us becausethey knew they could sensationalize andget a lot of emotion behind this area. Andwe acknowledge that it's a very importantissue. But that's why they call these thingstest cases, we're having to bear the burden,if you will, of going forward. Now, I knowthat as of Friday there are 15 or so amicusbriefs who have either filed in support ofus or posturing a position in support ofpatents. So we're the named party, butwe're not alone in this.

I know Myriad is not alone in its posi-tion, but this appeal must cost asignificant amount of money. It seemsthere was an option not to appeal thedecision, and if it's not important toMyriad's business, why take on all thecourt costs? Or am I wrong-is anyonehelping out with the costs?

Nope, it's just us, there's no one spon-soring us or supporting us. We're footingthe bill entirely on our own. It's just a factof life when you're in the business world.You hope to avoid it, and you try to avoidit when you can, but that's just litigation.


It does seem that the initial research toisolate the BRCA genes would have hap-pened anyway.

We can all speculate. We have to takea step back and consider the big picturehere: If we're wondering whether thepatent system works, we shouldn't let a sin-gle isolated case rule what's mostappropriate. In this case, yes, there wereother groups looking for it, and I presumethey would have found it. But that gets tomy point before: discovery alone doesn'tcommercialize and promote the science,all it does is result in discovery. There havebeen lots of discoveries that have nevermade it to the market for a variety of rea-sons. But you're right, there were othergroups looking for the BRCA gene, and Ipresume would have found it … but Myr-iad found it first.

Myriad recently offered to surrenderone of its gene patents in Australia. I'veseen various speculation as to why … canyou clear up the reasoning behind thatdecision?

It's always comical to sit back and lis-ten to the speculation, when if they wouldjust call and ask we could enlighten them.In Australia, we actually don't have thecommercialization rights. Ten years ago,we gave that to a company called GeneticTechnologies. They have the exclusive

rights to commercialize BRCA testingthere. As a matter of their commercial-ization strategy, they had earlier made a"gift" of the patents. They can't make a giftof the actual patents, but they told the Aus-tralian people, "We are not going to enforcethese patents against anyone." In otherwords: "We'll compete with anyone elsejust on the quality of our testing."

So, when this lawsuit came, it was kindof a copycat of the U.S. case-the nonprofitbringing the case picked Myriad sincethat's what they did in the U.S. Well, whenwe got sued, we said, "Wait a minute-thepatents aren't being enforced against any-body. Everyone's free to practice thepatents. There's no issue here." The prob-lem is we're now being forced to spendthe patent litigation costs, literally millionsand millions of dollars, and our initialresponse was, "Why would we spend mil-

This lawsuit will not have an impact on Myriad. It’s going to have a muchgreater impact on the biotechnologyindustry as a whole.


Senator Edward Kennedy once saidthat the mapping of the human genomewill "affect the 21st century as profound-ly as the invention of the computer or thesplitting of the atom affected the 20thcentury." Indeed, it's already hard to keepup with the rush of information andopinion coming out as the result of therapid growth in genetic research andtechnology today. Even without our fullyrealizing it, genetic technology is enter-ing almost every area of our lives, fromhuman health and reproductive tech-nologies to the criminal justice system.Genetic testing is becoming mainstreamand the opportunities to reveal geneticinformation are multiplying. An individ-ual's genetic information has incrediblevalue in a host of areas where invasionsof privacy and potential discriminationare present; it is both highly identifiableand provides a window into your healthand even the health of your family mem-bers.

Most consumers lack a proper under-

standing of genetics and it isn't hard tounderstand why. To the degree that thepublic has any background in genetics, itis often distorted by everything frompopular culture to consumer advertising.The media regularly covers the latestgenetic "breakthrough" and widely dis-tributes exaggerated claims. The Internetoffers little clarity; even consumers whowant to seek a basic understanding ofgenetics and "Google" DNA will findapproximately 143 million and growingsources of information, along with 10million for "genetic engineering" andalmost 2 million for "DNA and altering."

The consumer has even less under-standing of the privacy threats involvedin releasing their DNA or other forms ofgenetic information from issues of acces-sibility to storage of genetic informationand their associated risks. The extremelyvaried legal and regulatory framework ofprotections in areas where genetic infor-mation is acquired poses significantadditional barriers to consumer under-

standing. The consumer is highly unlike-ly to fully appreciate the value of theirgenetic information and make informeddecisions about its use. As a result, mil-lions of people's privacy is regularly andoften unknowingly compromised.

The Council for Responsible Genetics'Genetic Privacy Manual: Understandingthe Threats- Understanding Your Rightsis a comprehensive, electronic source ofinformation for the consumer on theseissues. The manual consists of five majorsections:

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The Council for Responsible Genetics’ Genetic Privacy Manual

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Can the discoveries from genetic sciencebe patented? There is a tension between theincentives created by the patentsystem–rewarding the disclosure of newknowledge with exclusive rights–and thenorms of scientific research–disclosing newknowledge for further scholarly investiga-tion. The intellectual force of reductionismin the life sciences, deepening the investi-gation of molecules and relationships thatexplain biological phenomena, generatesdirect conflicts with patent law's exclusionof basic knowledge from patenting. Foremerging fields of science and technology,this tension surfaces immediately: the schol-arly imperative to dive in and work on anunfettered intellectual landscape may clashwith new possibilities for commercial devel-opment. The result is that a new scientificfield may emerge that is immediately dot-ted with fences and boundaries-the patentsthat structure how its knowledge can beused.

Genetic science has not been immune tothis conflict. The era of genes and genetictesting has proceeded alongside concernsthat patenting efforts, in some instances,have unnecessarily reduced access forresearchers, clinicians and patients to med-ical significant genes and methods for theiruse. That outcome is troubling becausegenetic medicine represents a paradigm shiftin which disease is explained and treatedaccording to genetically-dictated biochem-ical mechanisms. Genetic testing can be usedto identify disease susceptibility, to establishdiagnostic status, and to design personalizedtherapeutic regimens in medical care.Adverse patenting not only limits scientificresearch; it also impacts patient care. We arenow approaching the resolution of two sep-arate challenges in genetic patenting. Cangenes themselves be patented? Can the sci-entific correlation between a gene mutationand disease susceptibility be captured as apatented method of genetic analysis?

Not everything can be patented. TheSupreme Court has been quite clear that"laws of nature, natural phenomena, andabstract ideas" are not patentable, althoughthe interpretation of this maxim has beendifficult.1 Yet the underlying rationale is that

scientific advances depend on an availablesubstrate of basic knowledge, and that, there-fore, patenting the intellectual foundationsof a field has an adverse effect on itsprogress.2 The patentable subject matterdoctrine in patent law, patent eligibility, per-forms this necessary gatekeeping function.3The patent eligibility of genes and geneticmethods can be decided by comparing theseclaimed inventions against the establishedexclusions of "laws of nature, natural phe-nomena, and abstract ideas" from patenting.

There is a paradoxical element to thepublic debate over patents pertaining togenetic science. While patent eligibility forinventions in genetic science has generatedsignificant public controversy for years, untilrecently, it had yet to receive the formal legalreview by the courts that could resolve theissue. Many stakeholders who were con-cerned about gene patenting lacked anyformal standing to raise the issue in thecourts. Thus, it is no surprise that the recentcourt cases impacting the patent eligibilityof genes and genetic correlations would gen-erate intense interest.

The GenesIn Association for Molecular Pathology v.

United States Patent and Trademark Office4a coalition of professional medical organiza-tions, medical providers, researchers andpatients challenged the eligibility of "isolatedDNA" patent claims on the purified BRCA1and BRCA2 genes, alleging that genes areboth "products of nature" and "manifesta-tions of laws of nature" for which patents maynot be obtained.5 The judge accepted thearguments of the plaintiffs that the patent-ing of genes violates prohibitions againstpatenting products of nature or manifesta-tions of the laws of nature, and ruled that thechallenged patent claims were invalid.6 Theargument of the defendants–that the puri-fied gene is not a product of nature, but aproduct of invention–failed.

The debate continues: does purificationof a gene create a new product or does it sim-ply allow the DNA to be used for its naturalfunction? Must a product of nature be struc-turally or functional identical to its naturalcounterpart? If purified DNA is reenacting

its natural performance in the cell, then is"isolated DNA" really any different than thenatural form? Moreover, is the function ofDNA particularly special? All of these over-tones are apparent in the AMP case, andthe eligibility of DNA can be analyzed utiliz-ing patent law standards, without recourseto non-legal genetic exceptionalism. Thepurified gene is often claimed as an isolatedcomplementary DNA, or cDNA, the abbre-viated, message-bearing form of the gene, aresult of laboratory manipulation, reflectingdivergence from the physical genomicform.7 However, all of that structural invest-ment is done to preserve the naturalinformational content of the gene: the main-tenance of its functional identity. Thus, wemust ask what the product of nature doc-trine is trying to accomplish by prohibitingthe patenting of natural products. Theunderlying goal appears to be preservingaccess to natural products and knowledgewhere no truly inventive alteration has takenplace. It is obvious that the purified gene isvaluable precisely because it reprises its nat-ural behavior outside the cell. The purifiedgene is surely the clone of its cellular self, anda product of nature that cannot be patented.

However, there is more complexity. DNAis not like other biomolecules. It is impor-tant to understand the complex set ofattributes that distinguish DNA from othermolecules-its identity as both chemical andtemplate-and how these attributes impactthe patenting analysis. The discovery of thestructure of DNA ended the most impas-sioned search in the history of biologicalscience: to identify where genetic informa-tion was encapsulated and how it wastransmitted. The gene emerged as themolecular repository of an embedded code-the genetic code, a long-sought law ofnature.8 This code was deciphered in orderto establish how DNA instructs the execu-tion of proteins.9 The Human GenomeProject began to assemble the set of spe-cific embodiments–the genes–that accountfor human form and function.10 Genes arenature's exemplars of the genetic code; assuch, they embody this law of nature.11 Ithas long been established that "manifesta-tions of laws of nature [are] free to all men

Protecting the Intellectual Foundations of Genetic ScienceConcerns about patents accompanied genetic research long before the gene patent system got itsday in court

BY EILEEN M.KANE

and reserved exclusively to none."12 Follow-ing from the Supreme Court's dictate thatthe laws of nature are not patentable, it canbe concluded that the patenting of geneseffectively preempts the genetic code, and istherefore not allowable.13 This becomes aseparate analytic basis for concluding thatgenes are ineligible for patenting.

The Genetic CorrelationsThe patenting controversies in genetic

science continue. Can one patent the obser-vation that a mutation in a gene, such asBRCA1, is associated with a higher suscep-tibility to early-onset breast and ovariancancer? Can this scientific correlation becaptured in a patented method without run-ning into the exclusion of "laws of nature,natural phenomena, and abstract ideas" frompatenting? Maybe not. The AMP litigationalso presented this issue, asking whetherpatenting the method of utilizing the rela-tionship between a mutation in the BRCA1gene and a higher cancer risk was, in effect,the patenting of a natural phenomenon.Again, the judge sided with the plaintiffs,although the reasoning employed a legal testthat has now been discarded by the SupremeCourt in the business method patent case,Bilski v. Kappos.14 Other recent cases in thelife sciences focus on whether scientific cor-relations can form the basis for a patentedmethod: LabCorp v. Metabolite15 (a diag-nostic method for detecting a vitamindeficiency using the quantitative correlation

between the level of the amino acid homo-cysteine and several B vitamins), Prometheusv. Mayo16 (a treatment method using thecorrelation between a metabolite level anddrug toxicity to more precisely tailor phar-maceutical dosage), and Classen v. Biogen17(a method for optimizing an immunizationregimen utilizing the correlation betweenadministration and effect). Prometheus,Classen and AMP will now be recalibratedin the post-Bilski framework; the FederalCircuit will have an opportunity to revisit theeligibility of scientific correlations as patentmethod claims using the law of nature/nat-ural phenomena analysis. As a result of thefact that these important patent cases involv-ing method claims have been litigatedwithout directly reaching the public domainquestions embedded in the patentable sub-ject matter doctrine, the field awaits moredefinitive guidelines for how the detailedinvestigation of biological mechanism cancoexist with patent law's prohibition onpatenting basic and essential knowledge.

The significance of determining whetherscientific correlations are subject to patent-ing cannot be overstated. Beyond theidentification of the molecules that performbiochemical tasks, modern biologicalresearch focuses on determining dynamicintermolecular relationships and biochem-ical causation. The contested method claimsin biochemical or genetic testing are hetero-geneous, where a patent claim may cover, forexample, quantitative relationships between

molecules, the mechanism of pharmaceuti-cal metabolism, or the cause and effectrelationship between genotype and pheno-type. While the universe of biologicalmolecules may be finite, the set of relation-ships and interactions that define humanmetabolism are likely to be vast. Therefore,it is essential to establish whether everyobservation of molecular performance canbe converted into a patent claim. It is fair toconclude that the animating rationale forexcluding natural phenomena from patent-ing would apply to exclude these types ofpatent claims. For genetic science, this wouldtranslate as a prohibition against patentingthe fundamental genotype/phenotype cor-relations that underlie genetic medicine.

ConclusionThe article concludes that genes and

genotype/phenotype correlations form theintellectual foundations of the genomic erain science, and are the kind of basic knowl-edge tools that fall within the exclusionsfrom patentable subject matter. In the nearfuture, AMP will present the Federal Circuit,and possibly the Supreme Court, with theopportunity to settle these critical eligibil-ity questions for patent law. Resolution of theeligibility controversies in genetic patent-ing is important for genetic medicine andalso has larger theoretical implications. Thelife sciences await a definitive and moderninterpretation of the product of nature doc-trine and its scope, and a contemporaneousanalysis of whether and how correlations inthe life sciences are regarded as natural phe-nomena or laws of nature. Other scientificsectors are also impacted by any judicial reaf-firmation that basic knowledge cannot bepatented, such as nanotechnology and otherfields in the physical sciences.

The patenting of applied research andtrue invention can coexist alongside the pre-serve of open and available knowledge. Morenarrowly tailored patent claims in geneticscience can be imagined, including thera-peutic applications of genes engineered intospecific molecular constructs and the useof scientific correlations embedded withinspecific genetic testing protocols. Suchinventive precision will allow creative appli-cations of fundamental knowledge to emergeand legitimately solicit legal protection,while the intellectual substrates for geneticscience remain unowned. That is an optimalbalance.

Eileen M. Kane, PhD, JD, is Professor of Lawat Penn State Dickinson School of Law.


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to eye when it comes to questions of genepatent policy–he is generally more skep-tical of the value of gene patents in thecontext of genetic testing, and more appre-hensive about the potential negativeimpact of gene patents on future availabil-ity of genetic diagnostic testing.Nonetheless, we both agree that theapproach taken by the ACLU and the dis-trict court could substantially harminnovation in biotechnology by broadlyrendering genetic and biopharmaceuticalinventions ineligible for patent protection,regardless of their usefulness and nonob-viousness, and thought it important tovoice our concerns to the Federal Circuit.In this article, I summarize some of thepoints made in our brief.

The Role of Gene Patents in Incentiviz-ing Investment in Biotechnology

The U.S. Patent and Trademark Officehas a long-standing policy of permittinggene patents, and has issued thousandsover a period extending back more than30 years. The biotechnology industry hasbenefited greatly from this policy, andgene patents have played a critical role inincentivizing the sizable investment nec-essary to develop and secure marketingapproval for life-saving biotechnologyproducts, as noted in two authoritativereports from the Congressional Office ofTechnology Assessment published in 1984and 1991.3

Although the current controversyinvolves genetic diagnostic testing, histor-ically the most important role of genepatents has been their use in providingprotection for biologic drugs. For variousreasons, it can be difficult to effectivelypatent a recombinant protein itself, andbiologic innovators have relied heavilyon patents directed towards the geneticsequences used in the production ofhuman protein therapeutics. In effect,biotechnology gene patents play a roleanalogous to that of drug patents in thetraditional pharmaceutical industry.Indeed, a 2009 report issued by the Fed-eral Trade Commission concluded that

gene patents have provided the "fuel" forthe "R&D engine" bringing biologic drugsto patients.4

Gene patents have been more contro-versial in Europe, but there too the debatehas been resolved in favor of gene patents.Indeed, Myriad's European patentsdirected towards the BRCA genes werefound valid after being challenged in oppo-sition proceedings in the European patentoffice. Ironically, many of these issuedEuropean patent claims would appear tobe patent ineligible under the districtcourt's decision. If affirmed on appeal, theMyriad decision would cause U.S. patentlaw to diverge from European law withrespect to this important class of patents.

Insufficient Evidence of Harm ThatWould Justify Broad, Subject Matter-based Invalidation of Gene Patents

Initially, much of the concern overgene patents was based on a fear that theywould create a "patent thicket" that wouldimpede biomedical research. However,after more than a decade it is becomingincreasingly apparent that the fearedpatent thicket for the most part failed tomaterialize, at least in noncommercial,academic research.

DNA hybridization array technologies,as exemplified by the Affymetrix gene chipand Illumina bead arrays, were thought tobe particularly threatened by the humangene patent thicket. After all, these prod-ucts can involve the use of DNA moleculesrepresenting many thousands of genes ina single array, and it was assumed that withso many issued gene patents it would beprohibitively burdensome to obtainlicenses or patent clearance to make or usethe arrays. In fact, however, it appears thathybridization array technology has neverbeen the subject of a patent infringementlawsuit involving a gene patent (althoughthey have generated copious patent litiga-tion involving non-gene patents).

Today, most of the angst over genepatent centers around the potential neg-ative effect on genetic diagnostic testing.The recently released Revised Draft Report


In considering the policy implicationsof Association for Molecular Pathology v.United States Patent and TrademarkOffice (the Myriad decision),1 it is impor-tant to bear in mind that much more is atstake than the specific patents targeted forinvalidation by the plaintiffs in the case(the ACLU and Public Patent Foundation,referred to collectively herein as theACLU). The ACLU has garnered com-pelling emotional capital by stressing thealleged detrimental impact of the chal-lenged BRCA patents on patients sufferingfrom, or at risk of developing, breast can-cer. More particularly, much of thecriticism has focused on the alleged overlyaggressive patent enforcement practicesof the patent owner Myriad Genetics. Butinstead of mounting a legal challenge tothese particular patents, or to Myriad'spatent enforcement practices, the ACLUhas launched a broadside attack thatthreatens to render a huge swath ofbiotechnology inventions ineligible forpatent protection, particularly inventionsrelating to genetic discoveries. If the Fed-eral Circuit affirms the Myriad decisionon appeal, it could cause substantial col-lateral damage to future innovation ingenetic diagnostic testing, personalizedmedicine, and biotechnology in general.

Because of the potential for substan-tial unintended negative consequences,Robert Cook-Deegan and I have submit-ted an amici curiae brief with the FederalCircuit that supports neither party, buturges the Federal Circuit to reverse thelower court's decision finding the claimsat issue patent ineligible.2 Dr. Cook-Dee-gan directs the Center for PublicGenomics at Duke University, which con-ducted eight case studies of the impact ofso-called "gene patents" on genetic diag-nostic testing that were commissionedby the U.S. Secretary's Committee forGenetics, Health and Society and pub-lished in April 2010. We have both devotedmuch of our scholarship to the study ofhuman gene patents and their role inbiotechnology and genetic testing. Dr.Cook-Deegan and I do not always see eye

The Danger of the Broad BrushThe ACLU attack on gene patents threatens unintended consequences for biotechnology andnext-generation genetic testing.

BY CHRISTOPHER M.HOLMAN

ten description requirements as set forthin Section 112 are the appropriate doc-trinal tools for challenging overly broadpatent claims.7

Unfortunately, instead of using thesemore targeted approaches to challengeMyriad's patent claims, the ACLU has cho-sen to argue for a novel interpretation ofthe doctrine of patent eligibility which ifembraced by the courts would not onlyinvalidate the challenged claims, butwould likely substantially restrict or eveneliminate effective patent protection forgene-based inventions in general. Dr.Cook-Deegan and I argue in our brief thatpublic policy would be better served byemploying more conventional doctrinesof patentability to challenge gene patentclaims that appear overly broad, or whichare directed towards allegedly obvioussubject matter, thereby preserving the abil-ity of true innovators to obtain patentclaims of reasonable scope directedtowards useful and nonobvious gene-based inventions.

Much of the concern relating to genepatents has more to do with the enforce-ment and business practices of gene patentowners than with the patents themselves.For example, there has been little criticismof gene patent owners who enforce theirpatents to protect an innovative biologicdrug produced through recombinantexpression of the patented gene. Given thehigh cost and risk associated with bring-ing a biologic to market, most wouldconsider enforcement of gene patents inthis context legitimate. In contrast, Myr-iad's use of gene patents to maintainmarket exclusivity over BRCA testing inthe U.S. has been highly controversial.However, if society determines that thebusiness and enforcement practices of cer-tain gene patent owners is problematic insome contexts, it would be more appro-priate to consider alternatives that moredirectly address these concerns, ratherthan the ACLU approach which wouldbroadly preclude effective patent protec-tion for DNA-based inventions in general.

For example, since the real concernwith gene patents is the potential forrestrictions on research and genetic test-ing, a more targeted approach couldinvolve the creation of some sort of exclu-sion from infringement liability for thoseusing patented genetic technology inresearch or genetic testing. This is theapproach recommended in the SACGHSreport, and could be accomplished by sim-ply expanding the scope of a provision that

already exists in the patent statute whichshields healthcare providers from liabil-ity for acts of patent infringementoccurring during the performance of"medical activities." Alternatively, ifdeemed necessary, other approaches suchas compulsory licensing, invocation ofmarch-in rights, and assertion of state sov-ereign immunity could be considered.8

Potential Unintended Negative Conse-quences for Biotechnology

Looking forward, companies focusedon the development of pharmacogeneticsand personalized medicine–technologieswidely viewed as critical to the future ofpharmaceutical development of health-care–point to gene patents as critical forsecuring the funding necessary to bringthese products to market. If the FederalCircuit affirms the Myriad decision, itcould dramatically reduce the privateincentive for investment in innovation inthese and related fields. It could alsoundermine incentives for the developmentof new biologics, an increasingly impor-tant class of life-saving drugs.

Some would argue that gene patentsare not required to promote innovation ingenetic diagnostic testing, and this mightbe true with respect to patents on genesfor Mendelian medical conditions, such asthe BRCA genes. It does not follow, how-ever, that publicly funded research willsuffice to discover and develop the nextgeneration of genetic testing technologies,particularly those involving more complexpatterns of genetic variation involving alarge number of genes dispersed through-out the genome, or identification ofcomplex gene expression patterns. It alsoappears likely that at some point the FDAwould take a more active role in regulat-ing genetic diagnostic testing, and requirea submission of data to demonstrate safetyand efficacy, which could substantiallyincrease the cost of commercializing newgenetic diagnostic tests. These develop-ments could render the availability ofeffective patent protection critical forincentivizing the necessary private invest-ment to bring these technologies tofruition.

Christopher M. Holman, PhD, JD, is Asso-ciate Professor of Law at the University ofMissouri-Kansas City School of Law.

on Gene Patents and Licensing Practicesand Their Impact on Patient Access toGenetic Tests (the SACGHS Report),5 forexample, identifies a potential for a sub-stantial negative impact of gene patents ongenetic diagnostic testing, but concludesthat there is currently no conclusive evi-dence establishing that gene patents havehad a net negative effect on the availabil-ity of genetic testing services.

Critics of gene patents, and Myriad'sBRCA patents in particular, have allegedthat gene patents unduly raise the cost ofgenetic diagnostic testing. However,SACGHS looked for evidence that patent-based exclusivity resulted in higher costsfor genetic testing services and was unableto document any consistent effect. In fact,the SACGHS Report states that one "sur-prising finding from the case studies" wasthat the price of Myriad's BRCA test is"actually quite comparable to the price ofother full-sequence tests done … at bothnonprofit and for-profit testing laborato-ries."

More Targeted Approaches for Dealingwith Problematic Gene Patents andPatent Enforcement Practices

The ACLU could have chosen a moretargeted approach to address the perceivedproblems with the Myriad patent claims.For example, they argue that at the timeMyriad identified and characterized theBRCA genes their existence was well-known, and it was inevitable that one ofthe multiple laboratories actively engagedin efforts to isolate and sequence the geneswould have succeeded. In effect, they arearguing that the claimed inventions areobvious. But if that is the case, then theappropriate avenue for challenging theclaims is the doctrine of nonobviousness,as set forth in Section 103 of the PatentStatute.6

The ACLU further alleges that thechallenged patent claims are overly broad,completely blocking the ability of othersto perform any sort of genetic testing, orto perform research, and even prevent-ing doctors from communicating withtheir patients. In fact, this is probably agross overstatement of the actual scope ofcoverage that would be afforded theseclaims if Myriad ever sought to enforcethem in court. If a court were to interpretthe claims as broadly as the ACLU sug-gests, there is good reason to believe atleast some of the claims could be invali-dated for lack of novelty or obviousness.More generally, the enablement and writ-


Robert Cook-Deegan co-authored an ami-cus brief in the Myriad case with the authorof the preceeding article, Christopher M.Holman.

Professor Holman and I found commonground because we are both concernedabout the implications of eliminating allpatents on DNA-based inventions. To myeyes, the business model pursued by Myr-iad Genetics is problematic, and I wouldlike to see many of Myriad's broad claimsinvalidated and the scope of the patentsnarrowed considerably–probably more sothat Prof. Holman–but I share his concernthat the logic of Judge Robert Sweet'sMarch 29, 2010, ruling pushes in the direc-tion of eliminating the possibility of patentson DNA molecules.

Is DNA Patentable Subject Matter orNot?

The intuition that Judge Sweet capturedis that DNA is an embodiment of biologi-cal information, and one of its keyproperties is self-replication. This featureof DNA is the reason that Watson andCrick became household names. JudgeSweet recognized DNA's unique role as thestorage and transmission medium forgenetic information. It does not follow,however, that nothing made of DNA canbe patented. DNA can also be engineered,and forms of it can be discovered, even inunaltered form, that have value in alter-ing biology and possibly treatingdisease. If the higher courts agree withJudge Sweet, then the problems asso-ciated with gene patents indiagnostics will indeed be gone, butsome good things will be gone withthem. Moreover, there is anotherway to get the same result withoutthe secondary consequences ofeliminating all DNA patents.

The Department of Justiceamicus curie brief

argues that JudgeSweet has been toobroad, and thatsome DNA mole-cules should bepatentable-those

that have been engi-

neered or altered–but that DNA sequencesfound in nature should not be patentablesubject matter. I am sympathetic to thisview, but I do worry that it will be difficultto hold that line. Some things that couldcreate social benefit if patentable wouldbe swept away, and I suspect courts willbe sympathetic to conferring the patentincentive for such products and services. Iam thinking in particular of DNA vaccines,small interfering RNAs and DNAs, andother objects that may be found in naturebut might also be molecules of therapeu-tic value in and of themselves. If so, theywill be expensive to develop into biologictherapeutics, in which case the patentincentive would serve the same role it playsin small molecule drugs and protein ther-apeutics (including some "gene patents"underlying those products).

The problem with Judge Sweeet's logic,and probably even the Department of Jus-tice position, is collateral damage to sociallyvaluable patents underlying therapeutics,and possibly also to future diagnostics thatwill be expensive to develop. That riskwould be much less if traditional doctrinesof patent law–such as novelty, obviousness,enablement, and adequate written descrip-tion–were used to root out destructivelybroad patent claims on BRCA and othergenes relevant to diagnosis, instead of asweeping rule about whether DNA ispatentable subject matter.

"Discoveries" Are Sometimes Patentablein U.S. Law

One argument marshaled against "genepatents" is that they are discoveries and notinventions. Genes associated with disease(or biological function) are indeed discov-eries that are not invented by theirdiscoverers, but so are many otherpatentable things such as antibiotics, vac-cines, and hormones which are items foundin nature. Social benefit arises from patent-ing such inventions when they requiresubstantial investment to develop into mar-ketable products or services. Geneticdiagnostics have generally not required thatkind of investment, but future diagnosticsmight, and some DNA-based inventionsclearly will if they prove therapeuticallyuseful. Examples include DNA vaccines

(including perhaps even naked purifiedDNA derived from natural pathogens),inhibitory RNAs and DNAs, or naturallyoccurring genes that may eventuallybecome treatments through gene transfer.If so, they will have to be clinically tested inexpensive trials, and the patent system isone way (admittedly not the only way) toinduce investment in such clinical studies.

Much of the argument about the BRCApatents claiming DNA molecules centerson what it means to "isolate" DNA; butDNA sequencing by definition entails "iso-lating" a DNA molecule in one way oranother by clever laboratory manipulation.So I agree with Judge Sweet's convictionthat the words "isolated" or "purified" inpatent claims are basically "a lawyer's trick,"but I do not agree with his logic that thisimplies DNA cannot be patented. Manip-ulation entailed in sequencing by definitionentails the hand of man, and it is thereforehard to distinguish this use of DNA fromthe other valuable molecules found innature that are now and have long beenpatentable. I don't think his line will holdin law; I do think, however, that the tradi-tional criteria for patentability (as opposedto patent-eligibility or patentable subjectmatter) if properly applied would reduceDNA inventions to the scope of what is dis-closed in the patent.

Applying Criteria of Patentability CanReach the Same End

If banning DNA patents were the onlyway to solve the problems in DNA diagnos-tics, I might agree with Judge Sweet's rulingand the Department of Justice position. Butthat is not the only remedy to problematicclaims in gene patents that have beengranted. Many of the broadest claims in thepatents being contested could be foundinvalid if subject to challenge in court.Before this case, there was no case law inthe diagnostic context, and courts couldnarrow patent claims relevant to genetictesting–particularly from the U.S. Patentand Trademark Office (which has beenmuch more prone to granting broad patentclaims than the European Patent Office).The problem is much more about overlybroad patent claims than whether patentson DNA exist at all.


The Overstated CaseUnduly broad claims are the problem, not DNA patents themselves

BY ROBERT COOK-DEEGAN

My argument is that rather than elimi-nate DNA as patentable subject matter, itwould be better to allow DNA moleculesto be patentable, but then apply the doc-trines of patent law rigorously to eliminatethe broad claims that have been granted.Current claiming practice in gene patentsallows claims covering discoveries that takeyears of hard work, long after the patent isgranted, to reduce to practice. Those prac-tices need to change. Case law wouldaddress the problems of diagnostic patentsby limiting their scope to what "inventors"actually contribute, and not more.

Two examples are directly pertinent tothe BRCA case. One is about claims onDNA molecules and the other about meth-ods for detecting DNA sequence changes.Claims 5 and 6 of the original BRCA DNAmolecule patent (US patent 5,747,282)claim any 15-base pair segments of DNAthat have a sequence that would encode aBRCA peptide. Only a court can decidepatent claim validity, but that claim seemslikely to fall afoul of two patent criteria:novelty and enablement. What is claimedis not novel because it in effect covers anyDNA sequence that encodes any fiveamino-acid sequence in any protein thatis the same as any five-amino acid sequencein BRCA1. It turns out there are a lot ofDNA sequences that encode at least fiveamino acids that can be found in theBRCA1 peptide, and some of them werein GenBank more than a year before thepatent application was filed. Moreover,while Myriad et al., did make it possible todetermine those sequences, they have notfound a use for the vast majority of the mil-lions of 15-mers they claim. If they hadrestricted the scope of the claim to muta-tions they demonstrated to confer risk ofbreast and ovarian cancer, they would havesome grounds for having enabled theirinvention to be useful. Claims 5 and 6 asgranted are extremely broad and thus prob-ably invalid, on grounds of novelty andenablement. If they fall, would other claimsblock BRCA1 diagnosis? The main inde-pendent claims (1 and 2) would not beinfringed, because no one makes andsequences a full-length cDNA for diagno-sis. To the degree that other claims areinfringed, they might be vulnerable to thesame problems of novelty and/or enable-ment as claims 5 and 6, unless they wererestricted to the very specific mutationsdisclosed in the patent. And if they were sorestricted, they should not confer a monop-oly for genetic testing.

Myriad also has method claims that arequite broad. Claim 1 of their main BRCA1

"method" patent is basically a very wordyand convoluted way to claim comparing asample sequence to a reference sequenceand noticing if there is a difference. Theutility, however, comes from knowingwhich alterations are associated with dis-ease. The claim does not restrict itself touseful comparisons described in the patent.Again, if the claim were only on a methodfor detecting differences that were knownto confer risk and disclosed in the patent,it might be specific enough to pass muster,and be enabled by the patent disclosure. Butif it were restricted to what was enabled atthe time of the patent application, it wouldnot allow Myriad to block others from test-ing for new mutations, and while Myriadwould have earned a right to licensing roy-alties for the mutations they worked hardto correlate with disease risk, they wouldnot be in position to assert a monopolyfor mutations they never discovered or hadnot yet discovered. Others might well findnew mutations, and if they patented them,Myriad would have to license them to dogenetic testing. This is how PGxHealth'smonopoly on testing for long-QT syn-drome was broken, when GeneDx securedcountervailing exclusive rights to long-QTmutations. Myriad's U.S. business modelwould have to change (and the UnitedStates is the only jurisdiction in which Myr-iad has been able to establish dominance asthe sole provider of BRCA testing). Theirbusiness model is the problem, not theirpatents, if properly interpreted. Theextraordinary breadth of the claims and thecost of pushing back against Myriad's ini-tially aggressive patent enforcement wereindeed enabled by their patents, but it is notnecessarily to kill all gene patents to rein inthe business model. Indeed, ACLU and thePublic Patent Foundation may have alreadyachieved much of what they desired bymaking clear that patent-holders trying toenforce gene patents in diagnostics maywell lose, especially if claims are undulybroad.

I truly believe there are serious prob-lems in DNA diagnostics that areassociated with patent rights, especiallywhen those rights have been exclusivelylicensed to a single provider. But if legaldoctrines of patentability were properlyapplied to gene patents in light of how diag-nostics work in the real world, monopolybusiness models would not be possible.

DNA Patents Are Not the Problem, butUnduly Broad Claims

One virtue of gene patents in diagnos-tics is that they reward inventors and their

institutions for some of the value they con-fer through their discoveries. I believe theUniversities of Michigan and Torontodeserve the royalties they have earned fromuncovering the cystic fibrosis gene, forexample-and other universities and inven-tors who found mutations later have alsoearned royalties from CF testing. Moreover,if the CFTR gene had proven useful forgene therapy, it is hard to see how it wouldhave been developed into a therapeuticwithout exclusive patent rights in the gene.

So it was right to patent the CFTR gene,and Michigan has licensed it for diagnos-tics in a way that has not hinderedinnovation or clinical access.

My view of the problem with the BRCAstory is not that patents are the root of theproblem, but that unduly broad claims weresought and granted, and then Myriad pur-sued a monopoly business model enabledby those mistakes.

Rather than proscribe DNA patents, itseems wiser to allow them, but restrict theirscope by applying criteria for patentability.This would reward universities, companies,and inventors with royalties they justly earnthrough their valuable contributions, butnot more than what they disclose anddeserve. Allowing DNA claims that meetcriteria for patentability would also pre-serve the exclusive patent rights that mayprove important in developing therapeuticmolecules based on DNA that will beexpensive to prove safe and effective in clin-ical studies.

Judge Sweet and the Department of Jus-tice have done a great service by forcing areexamination of patent policy as it per-tains to DNA diagnostics. I am sympatheticto their goals, but their means are undulybroad.

Professor Holman and I thus agree thatit is a mistake to stipulate that DNA is notpatentable subject matter as a matter of law.It would be far better to admit DNA mol-ecules to patent eligibility, but let the otherdoctrines of patent law do their work. Bynarrowing patent scope, we should get thesame result in diagnostics, but without thecollateral damage to DNA patents that maybe therapeutically useful.

Robert Cook-Deegan, MD, is Director ofthe Center for Genome Ethics, Law and Pol-icy at the Institute for Genome Sciences &Policy, Duke University.


If legal doctrines were prop-erly applied to gene patents,monopoly business models

would not be possible.

Daniel Ravicher, JD, is a Lecturer in Lawat Benjamin N. Cardozo School of Law atYeshiva University and Executive Direc-tor of the Public Patent Foundation, aplaintiff in the Myriad case.

How far back does the debate about lifepatents date?

There has been a debate about whatshould be patent eligible subject matterfor centuries. It's a constant debate.When new technology comes to the fore-front, the debate then gets mapped ontothat technology; so when we havebiotech, or genetic sequencing, or nan-otech, or software, we get all these newquestions about where should patentsplay a role in that new field. But the issueof what should be patentable isn't a newissue whatsoever-it's as old as our coun-try.

Why do you think it has taken this longfor a serious challenge to gene patentsto emerge?

I don't know, but maybe there haven'tbeen parties motivated enough to actu-ally bring the challenge, since there hadnot been enough financial impact yet. Webrought this case not from financialmotivation, but because we were moti-vated to serve a public good. There havebeen other gene patent cases, but mostof the time they were between partiesthat both have gene patents-so neitherside actually wants to allege that all genepatents are invalid, they just want toaccuse the other one of having unde-served patents for obviousness or someother lack of scientific merit.

At times there can be a certain 'yuckfactor' in the way that gene patents areportrayed, whether purposely or not,especially when it is framed as compa-nies owning our bodies. Do you thinkthat thinking misses the point, or isthere something to it?

Well, what's in our bodies or not inour bodies is not a clear demarcation.The law says you can't patent somethingthat is effectively nature, and the only useof genes isolated from the body is thatthey exactly replicate the genes in ourbody, or else they don't tell us anythingabout us.

It seems the legal issue primarilyrevolves around whether an isolatedDNA molecule is markedly differentfrom its counterpart as it appears innature-

That's the legal test set forth inChakraborty, yes.

Do you think that test makes the mostsense?

Yes, there has to be some borderbetween what is patentable and what isnot. The purpose of patents is to encour-age progress, to make the world a betterplace-not just to patent the world as youfind it. What makes something better ismaking a significant, substantial change,to take what God or nature hasgiven us and actually do some-thing with it. I think that testmakes sense as a policy pointand as a legal marker, becauseit's an adjective that has a littlebit of fuzziness to it, whichallows it to be custom-tailoredin appropriate circumstances.

You and others have said thatmost gene patents are notbeing enforced in a way that isharmful to the public since they arebeing widely licensed. Is there a legaldistinction between companies thatare reasonable or unreasonable in theway that they manage their patents?

The difference is that if a company isaggressively asserting its patents, it canbe subject to a declaratory judgment law-suit like we filed against Myriad; if a

company isn't being that aggressive, thereis no case or controversy that would sup-port a lawsuit. So if a company haspatents but are not asserting themagainst anyone, they don't have to run therisk of being sued in court like we suedMyriad. There is a legal distinctionbetween these two categories of actors.

Is there a test for that distinction, oris it another fuzzy boundary?

It's a fuzzy boundary, which theSupreme Court said it prefers in this areaof the law. In their Bilski decision, in theirKSR decision-in many decisions they'vehanded down, the lower court, the Fed-eral Circuit Court of Appeals, whichhandles all patent appeals, has been try-ing to come up with hard and fast rules,objective "true-false" statements, and theSupreme Court has said that's not theway the law should be applied. The lawshould be flexible and considered case bycase.

So would companies that are acting

in a way that you might call "reason-able" have anything to worry about ifthe case against Myriad is successful?

Even Myriad itself doesn't have any-thing to worry about, really, for itsbusiness model. It said to its owninvestors that even if it loses the case,it's not going to lose its business modelor revenue. We only challenged 15 claims


Some parties have said, “If this decision is upheld it will ruin the

entire biotechnology industry andplanes will fall from the sky,”

and that’s all just a bunch of crap.

The Sky Is Not FallingAn interview with Daniel Ravicher of the Public Patent Foundation

out of a total of over 100 claims. Even ifwe win, Myriad is still going to be in busi-ness, they're still going to be processingtests-this is everything they said to theirshareholders, that this isn't a financial riskto them. And we agree with that. Someparties have come in now and said, "If thisdecision is upheld it will ruin the entirebiotechnology industry and planes willfall from the sky," and that's all just abunch of crap. If Myriad itself is sayingthat it doesn't have anything financiallyat risk here, I don't understand how any-one else can allege that they haveanything to risk here. Patents are likesnowflakes: they're each different, andthey all have to be individually analyzed.Our decision may or may not have someimpact on the validity of other patents.Only time will tell.

If Myriad themselves are saying thatthey will be fine … are they still driv-ing the defense of this, or has it beentaken over by other actors claiming tohave something at stake?

No, they're still defending it, thoughI don't know why. But I haven't under-stood Myriad's behavior from day one, sothat's not unusual.

One of the other aspects of the gene

patent debate that comes up often isthe pragmatic end, the argument thatpatents have an incentivizing effect onbringing these tests to market.

Patents have a greater chilling effectthan incentivizing effect. Whatever yousay patents can incentivize, I can say theychill. Some people say they incentivizeinvestment; patents actually chill invest-ment to a greater degree than theyincentivize it. Some people say patentsincentivize research and development;patents actually chill research and devel-opment, there's no exception for researchfrom patent infringement. So the largereffect of most patents, which is provenby the empirical data which has beenpublished and not refuted by the pro-patent side, is that patents have a negativeeconomic effect, a drag on advancementof science.

Do you think this is the case across theboard, beyond gene patents?

Yes, the empirical data says that in thevast majority of industries, perhapsexcluding chemicals, patents have a netdrag effect on development. They siphonmoney away from R&D into the pocketsof lawyers.

I suppose this might be why many ofthe most vocal proponents of genepatents are patent lawyers.

They are the people who are finan-cially incentivized to promote theirsystem. You have to be skeptical of thepatent attorneys who say the sky is goingto fall and actually talk to the scientists,look at the real people, the businesses onthe ground, who say everything is goingto be fine. We can have a patent systemwhich respects individual rights andresearch, but which also provides theprotections that are necessary to createa net incentivizing effect on research anddevelopment.


GeneWatch Anniversary Archive: 1983-2008

The Council for Responsible Genetics was founded in 1983 to provide commentaryand public interest perspectives on social and ecological developments of biotechnol-ogy and medical genetics. For a quarter of a century, the Council has continued topublish its magazine GeneWatch with articles by leading scientists, activists, sciencewriters, and public health advocates. The collection of GeneWatch articles provides aunique historical lens into the modern history, contested science, ethics and politicsof genetic technologies. The full archive of GeneWatch has been incorporated intothis 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 DVDCouncil for Responsible Genetics5 Upland Rd., Suite 3Cambridge, MA 02140

25 Years of GeneWatch

Gene patenting is unquestionablycontroversial today, not in small part dueto the ACLU's lawsuit pending againstMyriad Genetics and the U.S. Patent andTrademark Office demanding a broadban on gene patenting. Actually, how-ever, the very term "gene patents" ismisleading. Patents are not, and havenever been, granted on genes found ina living body. Nor are patents grantedsimply on the information or codewithin a DNA sequence. Instead, patentsare granted on isolated and purifiedman-made DNA molecules that do notexist in nature and require a scientist'smanipulation to obtain. Simply put,without this manipulation, these isolatedDNA molecules would not exist.

For example, a type of isolated DNAmolecule that is claimed in manypatents, which is called complemen-tary DNA (or "cDNA"), is bothstructurally and functionally differentfrom genes found in nature. In fact,cDNAs do not occur in nature (nor arethey simply purified from nature).Rather, they are produced by making asynthetic copy of an isolated piece ofDNA that includes only parts (the pro-tein "coding regions") of the gene foundin the body.

Other examples include the shortsegments of isolated DNA, called probesand primers, which typically consist ofonly a very small portion of DNA of atotal gene. Because of the physical andchemical differences from genes in thebody, isolated DNA molecules (such ascDNAs) can be used in numerous waysthat genes cannot. For example, isolatedDNA molecules can be used: (1) to pro-duce large amounts of human protein innon-human species such as yeast, (2)to identify disease-causing mutations indiagnostic tests, (3) as medical treat-ments (e.g., gene therapy), and (4) aschemical reagents and research toolsto enable new discoveries.

Many of those who oppose thepatenting of isolated DNA moleculesarticulate serious concerns. These con-cerns include patient access to affordablecare, coverage and reimbursement forgenetic tests, the availability of secondopinion testing, and the appropri-ate scope of basic researchactivities that should be beyond thepurview of patent holders. Webelieve that these serious issuesneed to be addressed thoughtfully.However, a wholesale ban on genepatents, like that sought by theMyriad plaintiffs, would not allevi-ate these concerns. Rather, such asweeping, broad-brush approachwould cause wide-ranging disrup-tion to research and developmentfor innovative diagnostics andtreatments to the detriment ofindividuals and families in need ofmedical breakthroughs.

Not only do we believe thatgene patents can and should beused in a responsible manner toaccelerate medical research, tests,and treatments, we have first-handknowledge that it can be done.When my two children were diag-nosed with a genetic disease calledpseudoxanthoma elasticum (PXE),my husband and I worked intenselywith a team of scientists to discoverthe gene associated with the con-dition. After successfully cloningthe gene, we patented its corre-sponding cDNA and the method fordetecting it. The nonprofit organizationwe founded to be stewards of all that wasimportant to PXE, PXE International,now holds the patent and licenses it fora nominal fee. Although neither I nor theother co-patent holders receive incomefrom the patent, we deliberately choseto patent it in order to ensure (a) broadand affordable availability of the test, (b)that tests are conducted by quality

providers, and (c) all test results areadded to a mutation database hostedby the National Institutes of Health.Although there is still no treatment, areliable, accessible test alleviates the typ-ical nine year diagnostic odyssey. The

patent on the gene associated with PXE,which enables our mandate for publicdisclosure of results, focuses and accel-erates research and will eventually leadto an effective treatment faster thanwould a process devoid of the coordina-tion and control offered by the patent.

The law regarding gene patenting,despite being modified somewhat byevolving case law and regulation, hasbeen relatively stable–until the current


Why Banning Patents Would Hurt PatientsA wholesale ban on gene patents would not improve patient access to diagnostic tests, and itmight cause more harm than good

BY SHARON TERRY

Myriad challenge. The U.S. Patent andTrademark Office has issued thousandsof patents claiming isolated DNA mol-ecules and their uses, and in 2001 (inits patent Examination Guidelines) con-firmed explicitly that isolated DNAmolecules can be patented. IsolatedDNA molecules, as chemical com-pounds, are eligible for patent protectionbecause they are non-naturally occur-ring compounds, a product of humanactivity, and have a distinctive name,

character, and use. Therefore, as longas the claimed invention meets all of thestatutory requirements for a patent (i.e.,it is useful, new, non-obvious, anddescribed adequately in the patent appli-cation), a patent covering isolated DNAmolecules can be granted. Furthermore,until Myriad, the courts have not pre-viously questioned the patent-eligibilityof isolated DNA molecules. Finally, Con-gress has amended the patent statutes

numerous times in ways thatreflect its acknowledgementthat patents may be granted forisolated DNA molecules andtheir uses.

The biotechnology industryrelies on the well-settled prom-ise of patents covering theirinventions, provided, of course,that they meet all of the legal cri-teria. Biotechnology companies,many of which are very small

and very few of which are prof-itable, rely on patents to incentivizethe investment needed for researchand development of their productsand services. The cost of bringinga commercial biotech product tomarket, potentially $100 million ormore, and the reality that very fewresearch projects make it to mar-ket, combine to make innovationin biotechnology difficult at best.Given this, biotechnology compa-nies and their investors will notadvance these new technologieswithout the ability to recoup thesecosts during the limited time ofpatent protection. A sudden rever-sal of this investment-backedreliance on patent protectionwould be an unprecedented stepwhich would affect not only diag-nostics and treatments that rely onthese inventions, but wouldarguably affect a much broader cir-cle of innovative discoveries. Forexample, isolated DNA moleculesare used: (1) to test for infectiousagents, (2) to manufacture vac-cines, and (3) to produce proteinsused as therapeutics, and (4) inscreens to identify new drugs. Iso-

lated DNA molecules are also used inagriculture and other diverse industries.Therefore, a ban on "gene patenting"would not simply affect the companiesdesigning genetic tests, but would dam-age a multitude of industries withwide-ranging products. Taken to itsextreme, the arguments for why isolatedDNA molecules should not be patent-eligible may be applied to any isolatedmolecules, such as antibiotics and other

pharmaceuticals isolated from naturalsources.

A ban on gene patenting would slowdown the translational work needed tobring biomedical advances to the indi-viduals who are waiting for newdiagnostics and treatments. In addition,such a ban would not remedy the legit-imate concerns with diagnostic testssuch as their cost and coverage by insur-ance companies. Therefore, we believethat an unprecedented, wholesale banon gene patents would not alleviate legit-imate concerns and would create greaterproblems. Let's instead put this consid-erable energy into alleviating thecoverage and reimbursement for diag-nostics and therapy morass that willremain untouched by any manipulationof the gene patenting system.

Compiled with contributions from AnnWaldo.

Sharon Terry, MA, is President andCEO of Genetic Alliance and Presidentof PXE International.


A ban on gene patenting wouldslow down the translational work

needed to bring biomedicaladvances to the individuals whoare waiting for new diagnostics

and treatments.

On October 29, the United StatesDepartment of Justice filed an amicusbrief in the Myriad gene patenting case.While the brief supported neither party,it was lauded in the media as weighing onthe side of plaintiffs in opposing Myriad'sbreast cancer gene patents. The WhiteHouse recently announced its support ofDOJ's position, stating that patenting iso-lated genes would hinder innovation,delay advances toward the "revolution ofpersonalized medicine," and prevent theproliferation of diagnostic tests like theone at issue in this case. Unfortunately,these statements misrepresent DOJ'sactual position and the consequencesstemming from it, and, like much of thediscussion of Myriad, inaccurately glossover the complications of gene patenting.

DOJ supported the district court'sinvalidation of some of the challengedMyriad patents but not others. The 15challenged claims, covered by sevenpatents, roughly fall into two categories.One category of the challenged claimscovers actual molecules of DNA, or"compositions of matter," while the othercategory is comprised of "method"claims, where Myriad has claimed theprocess of comparing a patient's DNAsequence to known mutations in order todetermine whether she had a predispo-sition for breast cancer. Both categoriesof claims were invalidated by the dis-trict court.

The DOJ supported the invalidationof the method claims, but with respect tothe composition of matter claims it tooka different stance. The DOJ brief drew adistinction between the patents claimingnatural, isolated DNA that came from ahuman cell, and "synthetic" DNAs calledcDNAs that are made from the gene in atest tube. The DOJ took the position thatthe first kind of composition claims, theisolated human DNA, was a product ofnature and therefore unpatentable. Thesecond form of composition of matterpatents, however, were patentable

according to the DOJ. Because they werepurely man-made versions of the natu-rally occurring gene, and because theywere slightly different in structure andform, the DOJ argued these moleculeswere wrongly invalidated by the districtcourt.

The distinction drawn by DOJ takestoo formalistic an approach to bothpatent law and the nature of DNA.cDNAs, while different molecules thantheir corresponding DNAs, are differ-ent in ways irrelevant to the intellectualproperty Myriad has claimed. Genes inthe form of DNA in our cells, in order tomake the protein they encode, are firsttranscribed into mRNA. The mRNA,which is a perfect complement to thegene, then has certain portions ofsequence, called the introns, chopped outby an enzyme in order to create a maturemRNA that only contains the nucleotidesequences coding for the protein in ques-tion. This chopping process is calledsplicing. To make things more compli-cated, the mRNA can be spliced in manyalternate ways to produce sequences cod-ing for slightly different but relatedproteins. Once isolated from a human tis-sue sample in a test tube, these mRNAscan be converted back into complemen-tary DNA strands with the help of a viralprotein called reverse transcriptase. Thisis how cDNA, which stands for comple-mentary DNA, is produced. cDNAs areessentially identical to the naturallyoccurring, isolated mature mRNAs,except they have a different molecular"backbone" which makes them more sta-ble. The code-the thing that is valuable,the information that Myriad through itspatents has prevented others from usingin diagnosing and treating genetic pre-dispositions to breast cancer-is almostexactly the same. Thus, while in formthese are different molecules, in sub-stance and information, they areidentical.

The value of gene patents, whether in

cDNA, DNA, or mRNA form, is infor-mational content. As Judge Sweetpointed out in his opinion for the districtcourt decision, DNA is a unique and spe-cial molecule because it is the "physicalembodiment of information," and, morespecifically, "the physical embodiment oflaws of nature-those that define the con-struction of the human body." Thedifference between cDNA and isolatedDNA is like the difference betweenpatenting a mathematical equation (notpatentable under other patent law doc-

trines) saved on a computer and thatprinted out in a book. Saved on a com-puter it is perhaps "more stable" orpermanent, can be transmitted by email,can be integrated into software. Yet whilethe physical embodiment is differentwhen appearing on your screen or in aprinted book, the thing that one might(unsuccessfully) try to patent, in eitherform, is the same. It is purely informa-tional.

Importantly, by maintaining the valid-ity of Myriad's patent on cDNAs, theDOJ's position would effectively do verylittle to alter the current status quo withrespect to both gene patenting and thestate of breast cancer diagnostics. Cur-


The Physical Embodiment of InformationWhy the Department of Justice’s Myriad brief came up short on cDNA patents

BY MAGDALINA GUGUCHEVA

rently, any commercial diagnostic testmust use cDNA. Isolated DNA in its nat-ural form is not usable for thesepurposes. Furthermore, any research intothe BRCA1/2 genes requires the use ofcDNAs. By allowing Myriad to retainpatents over these cDNAs, diagnostictests for the purposes of promoting per-sonalized medicine would remain equallyhindered, and nothing would changewith respect to the market for breast can-cer gene testing.

DOJ has likely adopted its positionwith biotechnology products, rather thanmedical diagnostics, in mind. In order tomake any transgenic organism-geneti-cally modified crops, bacteria thatproduce important medicines from nat-urally occurring genes, and oil-eating

bacteria, etc.-cDNAs must be used.Thus, firms who discover genes with use-ful commercial biotechnologyapplications-for example, those genesinserted into crops to make them herbi-cide-resistant-would want to patent thecDNAs used to make those crops. Thisintellectual property is, especially in theinitial stages of product development, theonly asset that biotech startups can useto attract investors. Without this intel-lectual property, the claim goes, biotechinnovation would be stifled.

The claim that a prohibition oncDNA patents would deprive biotechstartups of their only property is false, yetit highlights much of the problem with a

binary approach to thepatentability of genes. Thequestion we should ask isnot, "are genes patentable?"but "at what point from thelocation of the sequence inthe genome to the develop-ment of a final, marketableproduct should we grantexclusive intellectual prop-erty rights to an inventor?"Once cDNAs are made,researchers can quicklymake more complicated molecules,called vectors. Vectors integrate thecDNA into a larger, more complicatedmolecule that can be used to insert thegene into other cells in order to make thetransgenic organisms at the heart ofbiotechnology. Myriad has patents outon many such vectors, and as the DOJimportantly points out, plaintiffs in thiscase never challenged those patents. Thevector, unlike the cDNA itself, incorpo-rates many elements that are functionally,not just formally, different than what onecan find in nature, and truly combinesnaturally occurring genes with non-nat-urally occurring inventions. The vectoris the starting point for all biotechnologyproducts arising out of gene discover-ies.

Myriad might counter that vectorscan't be used for diagnostic tests, thatonly cDNAs can, and therefore cDNAsmust be patentable to encourage thedevelopment of diagnostic technology.Yet the cDNA by itself cannot be useddiagnostically either; it must be inte-grated into a platform that will allow theresearcher to actually see if the patient'ssample binds to and compliments thecDNA. The cDNA needs some sort offurther alteration, creating an inventionthat does markedly differ from the nat-urally occurring gene in both form andfunction. Myriad's diagnostic technologyintegrating cDNA into a usable platform,like its vectors, are also not challenged inthe current case. Not only does this diag-nostic technology squarely fall withinpatent law, but more importantly, patentsclaiming it don't prevent others fromworking with the naturally occurringinformation in the genes as integrated

into other platforms. Patents on diagnos-tic technology merely prevent othersfrom using the same exact machinery-rather than information-in testing apatient for which version of the BRAC1/2gene it contains. Thus, invalidatingcDNA patents may prevent Myriad fromcharging absurdly high prices forBRAC1/2 testing by virtue of its monop-oly on the gene, but will still allow thecompany to retain enough intellectualproperty in the form of technology inte-grated with the gene to maintain itsvaluable position as the leader in theBRAC1/2 testing market.

Unfortunately, the DOJ brief hasmissed an opportunity to highlight theseimportant, consequential distinctionsbetween various "kinds" of gene patents,instead arguing difference where it doesnot really exist. The DOJ position woulddo very little for women currently unableto undergo breast cancer gene testing,and would fail to solve the anti-commonseffect currently resulting from exclusivelyheld gene patents. In order to strike thebest balance of encouraging innovationand preserving public access to naturalphenomena and information, patents onnaturally occurring genetic sequences inthe form of cDNA, as well as DNA andmRNA, should be invalidated.

Magdalina Gugucheva is a Fellow ofCRG.


The question we should ask is not, "aregenes patentable?" but "at what pointfrom the location of the sequence inthe genome to the development of afinal, marketable product should wegrant exclusive intellectual property

rights to an inventor?"

Over sixty years ago, Judge CharlesClark wrote that the function of courts"cannot be limited to a mere blind adher-ence to precedent." He cautioned fellowjurists against engaging in lofty formalism.Clark warned that judges must avoid cling-ing to precedent simply for the sake of itand "artfully" dodging new doctrine. Clarkrecognized the value of judges fully exer-cising their mental powers and"discovering and applying" new trends inlaw as the technology and policies of thetime demanded. Clark's pragmatic adviceto his colleagues on the bench remainstimeless.

Beyond a doubt, the burden of craft-ing judicial responses to nascenttechnology is a formidable process. Thestruggle today is not the relationshipbetween legal standards for the "old" lawof horse and buggy and the "new" automo-bile. Rather, the challenge for thecontemporary bench is determining theproper application of law and legal con-cepts to sexy new technologies andbiotechnologies such as the ownership ofgenetic materials, the regulation of genet-ically modified foods and organisms, andthe appropriate criminal and tort law stan-dards to mishaps, fraud, and breaches offiduciary duties.

Since the Supreme Court's landmarkdecision in Diamond v. Chakrabarty(1980), which made patenting livingorganisms legal in the United States, appli-cations for biologically derived patentshave taken off at break-neck speed. Withequal velocity and controversy have beenclaims of fraud, deception, invalidity, andunfair dealing in the relationships betweenpatients, medical researchers, and multi-national pharmaceutical companies. Incases ranging from Moore v. Regents,which involved the non-consensual takingand manipulation of a patient's geneticmaterials by his physician (1990), to morerecent cases involving the marketing ofinfected human tissues, judges stand in thegap of bumpy, unpaved terrain-often with-out legislative guidance. For somescholars, they are the principle arbitersbetween David and Goliath in this new

terrain. Yet, how judges view their rolesmay be very different than how the pub-lic conceptualizes their authority andobligations.

In Moore v. Regents, for example, theCalifornia Supreme Court found that thereis no such thing as one's ownership in hisbody. Moore lost on all but one count ina case involving over a dozen causes ofaction. Moore's critical argument was thathis doctor (also a medical researcher)acquired his spleen, semen, blood, andother biologics under false pretenses-essentially theft-and later capitalized andderived a patent on that which was con-scripted from Moore's body. The courtwas not persuaded by Moore's claimalthough there was no dispute about hisdoctor's unethical conduct in acquiringMoore's cell-line and other biologics. Formany years, this case has riveted law stu-dents attempting to reconcile intellectual

property law, property law, and the court'sdecision: how Moore's doctors couldown a patent (and profit) on a cellline derived from Moore's bodyand yet exclude Moore.

But a change may be under-foot.

Most recently, a lower courtdelivered a stunning blow to bio-pharmaceutical corporations inAssociation for MolecularPathology v. U.S. Patent andTrademark Office (better knownas the "Myriad Case") by rulingseveral very high-profile patentsinvalid. Myriad Genetics andthe University of UtahResearch Foundation ownthe patents on BRCA1 andBRCA2 genes, which aredefinitively linked tohereditary breast and


A Return to JudgingGenetics and biotechnologies in the courts

BY MICHELE GOODWIN

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ovarian cancers. The patents grant Myr-iad the exclusive right to performdiagnostic tests on the genes and hereinare the most significant problems voicedby critics. The tests cost over three thou-sand dollars per administration and havecontributed in large part to hundreds ofmillions in revenue earned by the com-pany in the last two years.

But some wonder, how can a gene thatis found in the human body of somewomen afflicted with breast cancer beowned by a corporation? The concernsover Myriad's patent involve the practical,theoretical, and conspiratorial. As withtraditional property ownership rights,owners possess the power to exclude, wardoff, and destroy property, and the author-ity to prosecute those that impose upon ortrespass against your property.

Understandably, this unique intellec-tual property status involving the BRCAmutant genes causes alarm. Among theplaintiffs’ claims is that in order for awoman to discover whether the patentedmutant genes exist in her body, she hasto pay Myriad for the test to discover what

is in her body. Particularly sensitive in thatcase is that the genes under dispute areassociated with ovarian cancer (BRCA 2)and breast cancer (BRCA 1), a disease thatremains incurable and afflicts 1 in 8women in the United States.

As a socio-economic matter, poorwomen without insurance could conceiv-ably be "priced out" from learning whetherthey might be at risk for breast cancer. ForAfrican American women (who are lesslikely to develop breast cancer, but fivetimes more likely than their white coun-terparts to die from it), the outcome of thislitigation and future appeals might be par-ticularly relevant. Myriad offers no realanswer to the underlying social-justice cri-tique voiced by critiques concerned aboutthe corporatization of medical knowledgethat could save lives.

However, Judge Sweets' District Court

ruling in the Myriad case was interpretedby some to be a guidepost for effectivejudicial decision-making in the biotechage. In the past, courts not only struggledwith evaluating the differences betweenhorse/buggy and car/train in tort law, butalso in contract, and even property law;but they took the leap, realizing that thebench could not fall prey to ambivalenceor myopic thinking. Notably, judgesdefined what those assignations wouldmean for people harmed by the technol-ogy. Judges were not blind to the economicdynamics of technology (i.e. incentivizingindustry and research) nor the politicallandmines associated with expanding civilremedies for individuals harmed by the

developing technologies. Increasingly, contemporary conflicts

in biotechnology mimic their predecessorsand will require an engaged, courageous,equipped judiciary. Metaphorically, con-temporary biotechnologies andcommercial usage of genetic knowledgeconverge like old locomotives on roadswithout guardrails and train crossingswithout lights, whistles, and signals. Thesocio-legal questions and problems ema-nating new technologies demand focusedattention from the judiciary.

Michele Goodwin, JD, is Everett FraserProfessor of Law at the University of Min-nesota.


Sheldon Krimsky is a founding memberof the CRG Board of Directors, Professorof urban and environmental policy andplanning at Tufts University, and authorof eight books and over 175 publishedessays and reviews.Tania Simoncelli is a former member ofthe CRG Board of Directors and ScienceAdvisor at the American Civil LibertiesUnion. She currently works for the U.S.Food and Drug Administration.

National DNA databanks were ini-tially established to catalogue the identi-ties of violent criminals and sex offend-ers. However, since the mid-1990s,forensic DNA databanks have in somecases expanded to include people merelyarrested, regardless of whether they'vebeen charged or convicted of a crime.The public is largely unaware of thesechanges and the advances that biotech-nology and forensic DNA science havemade possible. Yet many citizens arebeginning to realize that the unfetteredcollection of DNA profiles might com-promise our basic freedoms and rights.

Two leading authors on medicalethics, science policy, and civil libertiestake a hard look at how the United Stateshas balanced the use of DNA technology,particularly the use of DNA databanks incriminal justice, with the privacy rightsof its citizenry. Krimsky and Simoncellianalyze the constitutional, ethical, andsociopolitical implications of expandedDNA collection in the United States andcompare these findings to trends in theUnited Kingdom, Japan, Australia,Germany, and Italy. They explore manycontroversial topics, including the legalprecedent for taking DNA from juve-niles, the search for possible familymembers of suspects in DNA databases,the launch of "DNA dragnets" amonglocal populations, and the warrantlessacquisition by police of so-called aban-doned DNA in the search for suspects.Most intriguing, Krimsky and Simoncelliexplode the myth that DNA profiling isinfallible, which has profound implica-tions for criminal justice.

Genetic Justice: DNA Data Banks, CriminalInvestigations, and Civil Liberties

By Sheldon Krimsky and TaniaSimoncelliColumbia University Press

Contemporary biotechnologies and

commercial usage of geneticknowledge converge like

locomotives at train crossings without lights,

whistles, or signals.

In the gene patenting debate, as in war,truth has been the first casualty. Whetherit's publicity campaigns by the AmericanCivil Liberties Union with clever buttonsdeclaring "Do not patent my genes" orhyperbolic rhetoric, polemic has quicklyreplaced integrity in an effort to influ-ence public opinion (both at home andabroad).

A great deal of the anti-gene patentingargument is based on faulty premises,incorrect science, and a studied lack ofappreciation of patent law as it has beenapplied, inter alia, to patent-eligibility fornatural products. Since any rational debateis only as good as the information it isbased upon, it is useful to address the moreflagrant inaccuracies spouted by thosewho oppose gene patenting. Since "thetruth shall set you free," there are somefundamental truths that must be consid-ered when discussing gene patents. Theseinclude:

“Genes are a product of nature”: Thefacts

Patents claiming genes do not claimproducts of nature. The simple distinctionis that gene claims recite that the genes are"isolated," and this limitation on theirscope (as well as the 13th Amendment tothe U.S. Constitution) prohibit the sce-nario that a patent holder may one day ringyour doorbell and ask for a royalty fromyou because your liver is "using" a patentedgene. More importantly, no one wouldwant to own any individual person's genes:it has been known for more than fortyyears that any particular copy of a gene inan individual in a population is likely tocontain at least one polymorphism thatdoes or could (under the right environ-mental conditions) affect its function.Recent reports from J. Craig Venter on thecomplete sequence of human diploidgenomic DNA (his own) detected morethan 4 million nucleotide variants, includ-ing an extraordinary amount of geneticvariation that could affect gene expressionand gene products in unpredictable ways.

Moreover, and more significantly,human genes as they exist in human chro-mosomes are physically and chemicallydifferent from genes (really, isolated

nucleic acids) as claimed in the over-whelming majority of so-called "genepatents." Genes have been described,properly, as the instructions for produc-ing proteins. A gene encodes the aminoacid sequence of a protein in a linearsequence of 3-base triplet codons that cor-respond in linear order to the amino acidsequence of the protein. However, inhumans (and almost all other multicellu-lar organisms) almost all genes areinterrupted by "junk" DNA that does notencode protein (or at least does not encodethe same protein that the gene encodes).The entire gene, junk and codingsequence, is transcribed into RNA by thecell and then the junk pieces are "splicedout," leaving the coding sequence (termeda messenger RNA or mRNA) that is usedto produce the protein. Scientists takeadvantage of this process to clone genes,by isolating the mRNA and converting itinto a DNA molecule called complemen-tary DNA (cDNA), which is what iscloned, sequenced, and patented. cDNA

does not exist in nature, and must be cre-ated by man using chemical and biologicaltechniques. The hallmark of what theSupreme Court has declared is patent-eli-gible is "anything under the sun made byman." The cDNA copies of genes that formthe basis for human gene patenting are"made by man" and not products of naturebecause they do not exist in nature priorto being synthesized in a test tube by a sci-entist. If we are honest in defining whatare actually "products of nature," then theymust by definition be produced by nature.cDNA molecules are not.

“Genes are products of nature”: Thelaw

The legal argument that "products ofnature" are not patent-eligible proves toomuch, because if genes are not patentable

then many other natural products cannotbe, either. This includes for example var-ious antibiotics, and any number ofproducts isolated from crude oil, plants,animals, and even humans. If genes are notpatent-eligible, based on the fact that theyare products of nature, then the patentincentive cannot exist for these "prod-ucts of nature," either. If isolated humanDNA is not patent-eligible, there is noprincipled reason why many other "natu-ral products," such as antibodies,antibiotics, antisense and small interfer-ing RNAs (siRNAs), hormones,metabolites, and proteins should be.Importantly, also included in any such"natural products" patenting ban would bebiologic drugs, i.e., those drugs based on"naturally-occurring" human proteins.Indeed, proteins like human Blood Clot-ting Factors VIII and IX, insulin, humangrowth hormone, erythropoietin, tissueplasminogen activator, and all monoclonalantibodies are "isolated" in substantiallyhomogeneous form, are structurallyunchanged from their sources in bloodand other bodily fluids, and are less alteredthan the cDNAs that are the subject of theclaims to isolated human DNA invalidatedby the district court. These considerationsare also why the distinctions drawn in theDepartment of Justice's brief to the Fed-eral Circuit is bad science, bad law and badpolicy, in view of the expected importanceof biologic drugs in the years to come.

There is no binding legal precedentthat mandates that natural products areineligible for patenting. On the contrary,the prevailing precedent, Diamond v.Chakrabarty, mandates patent eligibilityto anything that is a "nonnaturally occur-ring manufacture or composition ofmatter - a product of human ingenuity,"that is "not nature's handiwork, but [theinventors'] own." Isolated DNA (as well asthese other examples of natural products)falls squarely within this rubric.

“Genes are part of a ‘commons.’”Ironically, genes and gene patenting

were originally assailed as creating a"tragedy of the anticommons," becauseprivate "ownership" thereof would impedegenetic research. In fact, as has been


Why Genes Must Remain Eligible for PatentingDispelling the myths about gene patenting

BY KEVIN NOONAN

There is no binding legalprecedent that mandatesthat natural products areineligible for patenting.

shown by multiple studies over the past 10years, gene patenting has done no suchthing. Indeed, every report on the subject,whether from the United States1, Ger-many2, Australia3 or Japan4, has foundthat "patent thickets"5 or the "anticom-mons”6 rarely affects the research ofacademic scientists. In addition, the incen-tive for gene patenting motivated privatecompanies, most notably Celera andHuman Genome Sciences, to competewith the federally funded efforts tosequence the human genome. This com-petition accelerated these efforts andproduced sequence information more rap-idly than anyone expected. If these effortsprovided genetic information that can beused to address human disease one day,one month, or one year earlier than itwould have been produced otherwise, whocan say the incentive is insufficient?

“Gene patenting inhibits geneticresearch.”

In fact, a very good case can be madethat the opposite is true. This is due toanother distinction glossed over by thoseopposed to gene patenting: genetic infor-mation isn't patented (despite the districtcourt's conceit that it could distinguishclaimed DNA from other biological prod-ucts for being "the physical embodimentof [genetic] information"). Patent lawrequires that claims be supported by awritten description sufficient to enable theskilled worker to make and use the inven-tion. For genes, this has meant that thegenetic sequence is disclosed in almost allgene patents. This information can beused for any number of purposes, includ-ing sequence comparisons (which can beperformed without "isolating" a gene),detecting genetic polymorphisms, and avariety of other scientific endeavors bothbefore and after a patent grants, withoutrisk of infringement.

Perhaps the best indicator that"inhibiting basic research" has not been aconsequence of permitting patents onhuman genes is the extent to which basicresearch has been performed on theBRCA1 or BRCA2 genes, famouslypatented by the University of Utah andlicensed by Myriad Genetics. The numberof research reports in public databasesreflecting ongoing basic scientific researchin peer-reviewed scientific journals onthese genes is almost 10,000: a simple data-base (PubMed) search of "brca1 or brca2"resulted in 7,855 publications. If either ofthe BRCA patents were to have had a chill-

ing effect on basic research, the expecta-tion would be that the number of scientificresearch reports would have declined inthe face of patent infringement liability.On the contrary, the number of such pub-lications has steadily increased each year,which is precisely what would be expectedif these patents had no significant effecton basic scientific research.

What these patents do, of course, isprevent commercial activity–i.e., using thepatented isolated human DNA or per-forming the patented methods for profit.This is a legitimate exercise of the patentgrant.

“We don't need gene patents–researchers will do it anyway.”

With regard to basic genetic research,this is true–it is the corollary to the pre-vious point, that gene patents don't inhibitgenetic research. However, there is a vastgap between identifying a genetic poly-morphism related to a disease, oridentifying a gene that encodes a usefulprotein, and developing a clinically vali-dated test or producing a commercialbiologic drug product, and that is wherebiotechnology companies come in. Ofcourse, without the prospect of patent pro-tection, investors are unlikely to providethe funding needed by start-up biotech-nology companies to develop commercialembodiments of these inventions. And inview of the complexities of biotechnol-ogy products, other avenues–trade secretsand regulatory data exclusivity being justtwo–may enable companies to keep their"monopoly" much longer than the term ofa gene patent. This would produce thekind of unfettered right in (undisclosed)genetic information that opponents ofgene patenting wrongly assert exists today.

“Gene patenting inhibits innovation.”It is easy to forget today the basis for

gene patenting in the past. Any number ofbiologic drugs have been developed that,according to a recent Federal Trade Com-mission report, "have improved medicaltreatments, reduced suffering, and savedthe lives of many Americans." These drugswere developed by companies that isolatedthe genes encoding them, including ery-thropoietin, human growth hormone,interferon, blood clotting Factors VIII andXI, human insulin, tissue plasminogenactivator, and a host of others. The patentincentive was instrumental in supportinginvestment in these companies and indeveloping a biotechnology industry in the

U.S. that has been a world leader for 25years. As anyone who followed the debateon follow-on biologics will recognize, theneed for patent protection to attractinvestment in what remains a fundamen-tally risky industry has not diminished.Patent policies abroad already permitthose countries to "free-ride" on Ameri-can innovation. Why should we adopttheir failed policies here? And who willcreate the next generation of drugs basedon biotechnology if we do?

Unfortunately, most of these argu-ments misconstrue the fundamentalsocietal benefit conferred by the patentsystem-not incentives to innovate, and noteven incentives to commercialize, but therequirements for disclosure that are fun-damental to the patent grant. The plaintiffsfatally overreached in seeking to invalidatethe patents-in-suit, and the U.S. DistrictCourt's decision, if upheld by the FederalCircuit or Supreme Court, is likely to haveunintended and seriously negative con-sequences. The patents at issue, directedto isolated human DNA encoding BRCA1and BRCA2, represent only the beginningof an era of personalized medicine that willbe characterized by understanding, andutilizing, genetic differences that impactboth an individual's propensity for suc-cumbing to diseases and disorders as wellas making a determination of the besttherapeutic interventions and treatmentsfor addressing them. Patents in this areaare needed to promote expeditious disclo-sure of the genetic bases for suchdiagnostic and therapeutic approaches tohuman disease; without them, alternativemeans of protecting such discoveries, forexample by holding them as trade secrets,will become more attractive. Patent-eli-gibility of isolated human DNA promotesnot only disclosure of the DNA itself (andthe proteins encoded thereby) but also thebest mode for making and using the iso-lated human DNA and related methods.Even should the basic genetic informationbe available elsewhere, failure to patentalso means failure to require full disclo-sure, and the attendant suppression ofinformation would affect the developmentof reliable drugs and diagnostic methods(or worse, permit private companies tohold such information indefinitely). Suchan outcome would be adverse to the pub-lic interest and contrary to the soundpublic policy underlying the Patent Act.

Kevin E. Noonan, PhD, JD, is a patentattorney and founder of patentdocs.org.


One frequent response to variousarguments against gene patents is theclaim that without such patents thebiotech industry will falter. There is verylittle evidence for this, and recently thetrend has been that corporations are seek-ing fewer patents on unmodified genes.This trend is no doubt motivated by recentshifts in the legal landscape creatinggreater uncertainty about the future ofgene patenting in general. The decision byJudge Sweet in the AMP v. Myriad case,the report of the SACGHS, and theDepartment of Justice's recent amicusbrief opposing patents on unmodified, butmerely "isolated" genes have necessitatedgreater caution in patent filings. If thesetrends continue, only modified sequencesare likely to remain patent-eligible. TheDOJ's brief sets the standard pretty low formodification, given that they concludethat cDNA is sufficiently inventive to bepatent-eligible; but all of this nit-pickingand dithering around the edges of patent-eligibility for genes, and bargaining amongparties who clearly believe that genepatents have some useful role in promot-ing innovation, seems odd to me. All ofthese arguments hinge on questionsregarding the efficacy, efficiency, and roleof gene patenting in encouraging innova-tion and economic growth. Utilitarianarguments are suspect to some of us withtraining in ethics, and of a particular eth-ical bent.

Utilitarian arguments can justify allsorts of nasty things, as long as the over-all good outweighs the harms caused.Utility can be a reason for doing some-thing, but it cannot, in my estimation, eversuffice if rights are otherwise violated.Those who believe in rights (and the dutiesthey imply) must reject the sole use of util-ity as an argument in favor of gene patentsif they violate some particular right.

In my book Who Owns You? The Cor-porate Gold Rush to Patent Your Genes, Iconsidered the various utilitarian argu-ments proposed by gene patentproponents, but argued ultimately thatthese pragmatic justifications were out-weighed by the fact that gene patents

violate certain inviolable rights. I didn'tarrive at those rights in the usual way. Iconcluded that even with gene patents, noone really "owns" you, nor can they claimto have any control over any one of us byvirtue of their patents. Even while patentson unmodified genes prevent you fromgaining information about your genomewithout paying monopolistic rents topatent holders, it is conceivable that thiswill be overcome by various technical pos-sibilities, such as do-it-yourself wholegenome sequencing. This is a remote anddistant possibility (anticipated and pre-pared for by the heroic Steven Salzberg, ofthe University of Maryland), but it illus-trates that the sort of control overindividuals posed by patent ownershipfalls short of violating our individualautonomy over our bodies.

Patents give to the patent-holder aright to exclude others from doing some-thing. In the case of gene patents, they givetheir owners rights to prevent others fromreplicating the patented gene. In most ofthe valuable instances of these patents,

that right enables a company (like Myriad)to prevent others from testing for the pres-ence of a certain mutation of BRCA1 and2 that causes an increased likelihood ofbreast and ovarian cancers. Granting sucha right to exclude is not unique to intellec-tual property law. It also is a hallmark ofreal property law. The term "real property"at one time applied to all tangible goods,but now it is generally understood to meansimply "land."

Many of us think that rights to own-ership of land and other tangible objectsis a natural right. The authors of the Dec-laration of Independence, taking their cuefrom John Locke, believed that certainrights were inalienable. Locke expressedhis view that "life, liberty, and property"were among the most crucial, inalienable,natural rights that inhere in all humans.The Declaration of Independence cites"life, liberty, and the pursuit of happiness,"although clearly the laws that were estab-lished in the various states and protectedby the Federal Government have long


Naturally Occurring Genes and the Commons by NecessityCertain essential parts of the natural world - like our genes - must remain part of the publicdomain

BY DAVID KOEPSELL

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All the legal fuss about gene patents maybe for naught. Operating under the beliefthat “any individual should be allowed tointerrogate his or her genome ... regardlessof whether a private company claims to‘own’ the rights to particular gene muta-tions,” Steven Salzberg, Director of theCenter for Bioinformatics and Computa-tional Biology at the University ofMaryland, and colleague Mihaela Perteacreated a program to screen an individual’sgenome for BRCA mutations–apparentlywithout violating Myriad’s patents on thosegenes. The software is available for freedownload, but there is a catch: you’ll needto have your genome sequence handy. Yetas the cost of whole-genome sequencingcontinues to drop, it will become more andmore economical to circumvent specificdiagnostic tests such as Myriad’s with com-putational screens. In other words, theSalzberg Screen just might be the harbin-ger of a future in which, at least indiagnostic testing, gene patents are essen-tially obsolete.

How is the Salzberg Screendifferent from anything that'salready out there?

It's the first purely compu-tational screen that starts withthe whole genome sequence–the "shotgun sequence" as wecall it–from sequencing yourgenome with one of the newsequencing machines, the socalled "next generation"sequencer.

I understand this project is adirect response to genepatents. Is it more specificallya response to the Myriad caseas well?

No, it predates that-weheard about that lawsuit afterwe had already done most ofthe work. We were just aboutto submit the paper when weheard about the lawsuit.

Was the main idea from the beginningto effectively circumvent patents?

I think you could fairly say it was oneof the main ideas. We just wanted todemonstrate that with current technology,we're now at the point where it's prettyeasy to interrogate your genome for anymutation that you want to if you have thegenome sequence. And you can do thatcomputationally: once you sequence yourgenome, it's a one-time assay. You cansequence your genome once and test itmany times-you can continue to test itcomputationally the rest of your life.Whenever a new mutation is discoveredthat you're interested in, you can justdownload some software and screen yourgenome. That's the way things will workin the future. We are a little ahead of thecurve, but that's the idea: in research, welike to be ahead of the curve. We're notthere yet, because people aren't routinelygetting their genome sequenced, but it'sgoing to happen, it's just a matter of time.

And the limiting factor now is the priceof whole genome sequencing?

Yes, the price of whole genomesequencing is now under $10,000, just todo the raw sequencing … but that's all youneed for our test, that raw sequence. Ourtest is free, the software is free, and youcan run it on your computer. It wouldprobably take all day or overnight, sincethere's a lot of data in a genome sequence,but you can probably do it on your desk-top computer. And the cost of sequencingis still dropping fairly rapidly. The Myr-iad test, which I believe is one of the mostexpensive, costs upwards of $4,000. We'realready pretty close to the same cost, andonce you have your genome you can testfor any mutation in any gene-so whywould you pay per gene to have themtested? It doesn't make any sense econom-ically.

You have said that "the door to this newtechnology is already open and cannotbe closed." Do you think that genepatents could get in the way of this?

Patents can slow things down and they

can get in the way, but I don't think thatthey are going to stop progress. They cer-tainly impede progress … but remember,the U.S. is not the only country in theworld, and the patents that are being filedin the U.S. are not recognized by manyother countries. So if you can't get yourgenes tested here, you may be able to gosomewhere else-the world is a small place.

Although it seems this software doesnot violate Myriad's patents directly, areyou concerned that they might sue youfor indirectly violating their patents?

I'm not really concerned, but I guessyou could say I have a mild concern aboutthat. I don't think it would really benefitthem to go after me. I think right nowMyriad is going to be mostly interestedin just keeping their patents from beingcompletely invalidated. The current courtruling is that the patents are not valid-andif that ruling holds up, game over for them.

For the very short term, you're notgoing to see large numbers of people get-ting their whole genome sequenced; butin the medium term, maybe four or fiveyears out, I think it's going to becomeincreasingly feasible for people to do that.If it's cheaper, people will do it.

If you can get one gene sequenced andtested for $4,000 or else get your wholegenome sequenced for $4,000 and thentest that one gene, I think everyone woulddo the latter, because once you sequenceyour genome you can then hang onto itand test for other mutations in the future-mutations that haven't been discoveredyet.

Have you had any pushback, anyonetelling you that making the screen avail-able was a bad idea?

No, not really. I talked to the peoplein my group about it, and they were all veryinterested in the topic. I'd say they mostlythought it was a good idea … though I'mnot sure they would have all done it them-selves!

To download the software, visithttp://cbcb.umd.edu/software/BRCA-diagnostic

Foiling Gene Patents: The Salzberg ScreenAn interview with the creator and namesake of the BRCA screen that circumvents gene patents


included rights to land and "moveables."But genes are clearly different, and patentsprovide a right to exclude that is differentfrom the exclusion granted by real prop-erty law. You are still allowed to keep thegenes in your body, you just have to payfees to know about their existence ifpatented. Regardless of its alleged utility,does this exclusionary right violate anynatural rights?

I concluded that it does, and in sodoing, expanded on existing theoriesabout the nature of what lawyers andeconomists have long called "the com-mons." The notion of a "commons" in theAnglo-Saxon tradition dates back to thepractice of sovereigns granting the publicthe right to use of certain parcels of thelands the monarch otherwise claimedownership over. Those who had no land,but maybe had some sheep, could grazethem on the commons. These were com-moners. If they could erect a shelter, theycould also own that enclosed shelter andlive there.

These ancient commons were what Icall a "commons-by-choice," as theyinvolve natural abilities of exclusivity. Thesovereign could have fenced and guardedthese lands, enclosing them, and exclud-ing all others from their use. Exclusivityis a necessary feature of the rights to own-ership of land and moveables. When Ipossess a hammer, or a house, I can phys-ically exclude others from it. To dispossessme of these things requires violence, andthe attempt to do so violates our naturalrights to our property. The mixing of mylabor with a parcel of land, its use, andmy ability to quietly enjoy that use, are allelements of basic Lockean theory aboutrights to property.

Intellectual property is utterly unlikereal property. The exclusivity created bythe laws of patent (which emerged muchlater than those regarding real property),is artificial, not natural. The state mustgrant, through some process of registra-tion, review, and agreement, a limitedperiod of exclusivity- a new and unnatu-ral monopoly right. There is simply nonatural way to exclude others from usingideas. But not all ideas can become thesubject of patents. The courts have longrecognized that laws of nature and abstractideas, for instance, cannot be eligible forpatent protection. I contend that this is notsimply a good, pragmatic idea, but ratherin accord with natural law. Abstract ideasand laws of nature are incapable of enclo-

sure or exclusivity because they belongquite clearly to what I call the "commons-by-necessity."

Unlike the commons-by-choice, thecommons-by-necessity includes any partof the universe that is incapable of enclo-sure. Laws of nature, like F=ma or E=mc2,are parts of the fabric of the natural uni-verse, having nothing to do with humaninvention. It is impossible to enclose andmonopolize or otherwise exclude othersfrom participating in them, utilizing them,or knowing about them. "Abstract ideas"are likewise commons-by-necessity. Thenecessity here is not pragmatic but logi-cal. There are simply some parts of theuniverse that cannot be enclosed, and thusthat are not amenable to ownership orexclusivity of any kind.

While the commons-by-choice couldbe owned through valid, useful possession,the commons-by-necessity can never be.Attempts by states, through patent laws orother means, to exclude anyone from uti-lizing commons-by-necessity, or to grantexclusive use to anyone over these sorts ofcommons, are unethical. This is notbecause of the consequences; as I men-tioned above, this is not a utilitarianargument. Abstract ideas, natural phe-nomena, and natural laws cannot becontained, cannot be exclusively con-trolled, and no rights may inhere for anyone individual over them. Unlike the rightsthat inhere over real property, there is nomanner in which anyone may claim anexclusive right over the commons-by-necessity. Instead, we all necessarily shareequal rights of access to these commons,not because some sovereign says we do,but because we are entitled to free, equaland open access to instrumental use ofnature's parts so long as that use does notinterfere with anyone else's rights. This isconsistent with John Stuart Mill's "Liberty"or "Harm" principle, which defines ourrights to liberty as broadly as possible, tothe extent that those liberties do not inter-fere with anyone else's. This is afundamental notion of modern liberaldemocracy.

There is thus an ethical reason why theSupreme Court has specifically excludedabstract ideas, physical phenomena, andlaws of nature from patent-eligibility (inthe seminal cases of Diamond v. Diehr andChakrabarty). These are all commons-by-necessity, free for use by any and all. Nosovereign could contain them, nor couldany individual. Unmodified DNA is, I con-tend, such a commons-by-necessity, just

as gaseous oxygen, the laws of gravity, thetheory of relativity, and all other naturally-occurring laws and phenomena are. Thegenes that patent attorneys claim are mod-ified through isolation, and thus somehowinventive, have pre-existed human inten-tion. Nature isolates them with promoterand stop codons, signaling the process oftranscription, characterizing them asgenes long before we ever developed the-ories about their existence, or confirmedthem through modern genetics. Identify-ing the sequence of naturally-occurringgenetic mutations, and using those discov-ery to help people anticipate, treat, andmaybe even cure diseases is very useful,and there are frequently inventiveprocesses and products involved, but thesequences over which companies likeMyriad have claimed exclusive ownershipbelong not just to the "common heritageof mankind," but to an un-encloseablecommons-by-necessity.

If we accept that there are such thingsas commons-by-necessity, and that whilerights to real property are grounded in nat-ural facts, no rights can ever obtain tocertain parts of the universe (like genes,laws of nature, physical phenomena, andabstract ideas), then we must reject thepractice of numerous gene patents cover-ing merely "isolated" genes as unethical.Certainly, some reject the notion thatthere are any ethical norms that aregrounded as I claim in natural states ofaffairs, and for some, ethics is somethingentirely man-made. For those, I ask: Onwhat basis are rights to life, liberty, orproperty based, and under which claimsof utility would you be willing to tradeaway any of these basic human rights? Ifwe are serious about our rights and recog-nize that some are inviolable, then we mustreject laws that seek to set aside or curtailthose rights for mere utility. Our mutualrights to access all commons-by-necessity,including genes, must outweigh thedesires by some to monopolize them, evenif their claims about practical necessity,innovation, and profit are true. Genesmust remain in the public domain, and itis not only contrary to established law, butmore importantly, it is unethical to allowpatents on genes that evolved due to nat-ural processes.

David Koepsell, PhD, JD, is Assistant Pro-fessor of Philosophy at Delft University ofTechnology and author of Who Owns You?The Corporte Gold Rush to Patent YourGenes.

Continued from page 32

I have always opposed the concept thathuman genes and their DNA sequencescould be patented. Not only did it appearto me that they were "a product of nature,"but the idea that some entity might haveownership to a chemical residing in nearlyevery cell of my body seemed offensive anduntenable. So it was apparently paradox-ical and sadly ironic that I felt compelledto join the opposition to the SACGHSreport on this topic that recommendedvarious actions against gene patenting bythe HHS Secretary. My opposition wasdistinct from that expressed by MaraAspinall and Sheila Walcott, who cosignedthe minority dissenting statement withme.

My objections were primarily based onthree points:

1. The patent system has spurred inno-vation and rapid commercialization in thelife sciences and medicine that has bene-

fited many people worldwide. We shouldhave a strong argument to disrupt a work-ing "good." The report did not adequatelyreflect this fact, nor did it include anymonitors or steps to preserve this effect,if it exists, in the field impacted by genepatenting.

2. The data demonstrating the harmscaused by the current system of patent-ing that includes "gene patents" were scantand not convincing in its specificity. Whilesome people surely have not had accessto patented products, most have; and oursystem of health care provision and financ-ing routinely discriminates against thepoor (and many other needy groups) gen-erally. The system needs change, butaltering patenting will not do it.

3. Finally, the report called for a vari-ety of Executive Branch actions (notablynot helping the ACLU case against Myr-iad). I believe the courts need to clarify the

current law on biotechnology patenting.Then, if we believe this legal regime aspracticed by the PTO is inadequate orinappropriate, laws to alter it should bepassed by the Congress. Executive actionprior to this process seemed ad hoc to meand could cause harms while curtailingimportant deliberations.

I therefore opposed some of the rec-ommendations and conclusions of thisSACGHS Report. I do hope that thisimportant issue will continue to bereviewed and litigated. A clear and widelyacceptable result that promotes humanintegrity and non-commodification whileproviding the hope that active researchand a fecund marketplace can bring tothose in need would be my goal.

Paul Billings, PhD, MD, is director andchief science officer of El Camino Hospital’sGenomic Medicine Institute and a mem-ber of CRG’s Board of Directors.


In Defense of a Working GoodBefore it was dissolved, the Secretary’s Advisory Committee on Genetics, Health and Societyissued a controversial report calling for limits on gene patenting - but it was not unanimous

Gene Patents and Licensing Practices and Their Impacton Patient Access to Genetic TestsReport of the Secretary’s Advisory Committee on Genetics,Health and Society

Statement of Dissent From Ms. Aspinall, Dr. Billings,and Ms. Walcoff

In our current health care system, patients routinely faceunequal access to medical care, including diagnostic tests. Con-sequently, it is our position that statutorily modifying the genepatents system, including the creation of exemptions from liabil-ity for infringement upon such patents as defined in this reportand proposed in the recommendations, would be more harmfulthan helpful to patient access and to the quality of innovativegenetic diagnostics.

The basis of our position is recognition that there are a vari-ety of financial and scientific decisions made by both governmentand private stakeholders throughout our health care system thatimpact patient access to genetic tests. We recognize the impor-tance of supporting and encouraging discovery and, mostimportantly, translating those genetic discoveries into new toolsto improve patient treatment and outcomes.

The patent system, although debatably imperfect, offers thosewho invest in developing discoveries a value for the investment.We believe that facts and findings cited in this report and in otherreliable scientific literature support our view that the recom-mended change to the patent enforcement statute and the

Bayh-Dole Act would have significant negative consequences.Many discoveries, in academic institutions or otherwise, may notbe pursued or developed. Notably, the increasing complexity ofdevelopment and clinical testing for genetic tests and higher evi-dentiary standards and regulatory hurdles such tests must meetrequire increasing levels of investment (measured in millions ortens of millions).

Notwithstanding our position that the recommendationsregarding the statutory changes to the patent system would notameliorate the patient access concerns this Committee has iden-tified, we do acknowledge and appreciate the importance ofpatient access and quality standards with respect to provision ofgenetic testing. However, while we agree that licensing does playsome role in universal access, public health plans such as Medic-aid and Medicare, as well as private payers, continue to be freeto refuse coverage and payment even if every laboratory in thecountry offers a test. Moreover, in addition to such reimburse-ment policy, other factors, including practice patterns andprofessional talent distribution, also impact what tests are con-ducted in what regions of the country. Therefore, we do notsupport the assertion that in most cases gene patents have had adirect and overarching negative impact on the ability of a patientto obtain a test.

In terms of clinical access on behalf of patients, our assess-ment of the data suggests that clinicians are often significantlylimited by contractual and financial barriers placed on them bytheir organization/institution or cost containment restrictionsimposed by public and private payers. The ability for every labo-

In the reporting and coverage of thecase against the United States Patent andTrademark Office and Myriad Genetics,the company holding the patents on theBRCA 1 and BRCA 2 genes, little has beenwritten about the ACLU's involvement ascounsel for the plaintiffs. Litigation regard-ing the rarified nexus of the science ofhuman genetics and the law of patentsappears at first glance to be different fromthe historic and well-established causes forwhich the famous advocacy group isknown. When considering the issuesinvolved in the process of patenting humangenes and genetic information, however,it becomes clear that the case is themati-cally related to those same traditions.Constitutional rights and civil liberties areat stake: the granting of exclusionarypatents to human genes and the informa-tion they embody restricts and infringesupon the guarantees of the First Amend-ment, freedom of speech and expression.

Although the decision of the lower dis-trict court in the case now under appeal atthe Federal Circuit did not reach the freespeech issue argued by the ACLU, the con-cepts involved in the argument areimportant for an understanding of thebroader context in which the gene patentcase developed.

Unique and emerging technologies ofthe "information age" present novel ques-tions for scholars considering the scope andmeaning of the First Amendment. YochaiBenkler's description of the creation ofthe digital environment and its resultantexpansion of intellectual property rights ininformation is representative of this newconsideration in First Amendmentjurisprudence and methodology. He assertsthat the challenge of supporting traditionalgoals of free speech and expression, "robustdemocratic discourse and personal auton-omy" is made more difficult by theinformation economy. Simply put, "To cre-

ate property rights in this economy, gov-ernment must often prohibit speech." Hedescribes the particular concern as "theenclosure movement in our informationenvironment. In other words, our societyis making a series of decisions that will sub-ject more of the ways in which each of ususes information to someone else's exclu-sive control," and notes that as intellectualproperty, we will expect "information to beowned, and to be controlled by its owner,"blinding us to "the cost that this propertysystem imposes on our freedom to speak."1

This evolving tension between the lawof intellectual property as delineated in theUnited States Constitution, Article 1, §8,clause 8 and the First Amendment has pri-marily been situated in the law of copyright,but a similar tension is developing betweenfreedom of speech and the patent system,where similar 'speech costs' undermine thesystem's Constitutional directive of "pro-moting the progress of science and the


Freedom of GenesThe Myriad case carries often overlooked First Amendment implications

BY DEBRA GREENFIELD

ratory to offer every test, in our view, is a commercial objectivemore than a patient access issue since clinicians can and do ordergenetic tests for patients every day from laboratories both acrossthe hall and across the county.

Nevertheless, we agree that the inability of certain populationsto afford genetic testing is an important and valid concern andshould be addressed directly as an integrated component of sys-temic health care reform. It is important that good intentions donot give way to negative outcomes in other parts of the health sys-tem or economy. As such, we would strongly encourage theDepartment of Health and Human Services to critically evaluatethe criteria and requirements of all public health programs, includ-ing Medicare and Medicaid, to ensure that every beneficiary ofpublic health funding has reasonable and timely access to genetictests regardless of income or geographic location. In addition,we strongly encourage HHS to evaluate relevant laws, regulationsand policies, such as anti-kickback, health care fraud statutes, andgovernment reimbursement policies, that are overly burdensomeor result in practical barriers on diagnostic companies who wouldotherwise elect to offer tests at little or no cost based on finan-cial need.

We also agree that testing, including quality standards,whether by a single laboratory or multiple laboratories, are animportant factor to the public's health. Test quality has been andshould continue to be appropriately addressed by the Food andDrug Administration and the Center for Medicare and Medicaid

Services. Specifically, those agencies should continue to worktogether to keep pace with laboratory and diagnostic innovationand identify new ways to evaluate proficiency, reliability, andreproducibility of new and innovative genetic tests. We do notbelieve, nor has FDA or CMS ever suggested, that there is anycredible evidence that the quality of testing performed in solesource laboratories is routinely or demonstrably subpar in any wayto that which is done in multiple laboratories. Nor do we believethat data indicate that modifying the gene patent system and pro-tections it offers through exclusive licensee agreements wouldresult in multiple laboratories performing proprietary tests withbetter quality than generated by current and developing oversightof quality assurance undertaken by these agencies and the labo-ratories themselves.

Finally, we believe that the determination of patentable sub-ject matter and the protections afforded to such patentable subjectmatter should remain the primary function of the US Patent andTrademark Office, Congress, and the US courts. The suspensionof patent protections such as exemptions from liability for patentinfringement for a restricted class of innovation (gene patents),unless they are determined to be non-patentable (for instance, acourt determination that they are a “product of nature”), is unwar-ranted and a risky intrusion in to a process that has delivered manykey innovations to needy Americans.

useful arts."2 Defined by the Patent Act asa property right granted by the govern-ment, inventors are rewarded with a twentyyear monopoly forbidding anyone otherthan the inventor from "making, using, sell-ing, offering to sell, or importing theirinvention."3 These grants are no longerconcerned with just artifacts of technology.Now, as commentator John R. Thomasnotes, "Patent claims, cut loose from phys-ical moorings, have grown more abstract."Examples include voter and consumer sur-veying techniques, marketing and salestechniques, and patented teaching meth-ods of language, music, vocabularyacquisition, dialogue writing, and mathe-matics.4

Thus, these unique questions as to whatthe framers meant by freedom of speechare raised not only in emerging informa-tion technologies but also in the emergenceof new practices in biotechnology. Descrip-tions of the science and language of thebiotechnology involved in human DNA isfrequently analogized to the science andlanguage of computer technology; themetaphors are abundant. Similar compar-isons can be made when considering howthe intellectual property grant of humanDNA patents results in tensions with theFirst Amendment. When DNA moleculesand DNA sequences, DNA sequences withsingle nucleotide polymorphisms (SNPs),replicated human DNA sequences (cDNA),and methods and materials for determin-ing a relationship between a particularDNA genetic sequence and the presence orabsence of a genetic susceptibility arepatented, speech concerns are raised.

A careful consideration of the decisionof the lower district court as well as thebriefs being filed in the appeal by Myriadreveal the importance of the basic under-lying question in the case considered withinthe context of gene patenting and civilrights and liberties: What exactly is thenature of the human BRCA 1 & 2 DNAmolecules and genes, and how can onecharacterize exactly what it is that is beingpatented? The briefs for Myriad describethe molecule isolated from its natural envi-ronment as simply "a chemical compound,"not distinctive from any other similarlypatented composition. The district courtfound the claimed isolated DNA to be in allrespects, identical to the same moleculeor sequence as that found in the body,known as native DNA, and that they haveidentical functions, the ability to expressBRCA 1 and 2 proteins. It is this structureand function that the court relied upon to

describe the essence of the patent claims as"embodied information," and thus distinc-tive from other chemical compositions."What is being patented is the three-dimensional structure of the chemicalbases that, in their ordering, direct the syn-thesis of other molecules in thebody-namely proteins."5

Thus newly characterized, the law inthe case this far is following the observa-tions and writing of social scientistsremarking on the nature of DNA in theinformation age, where "…biology is infor-mation, and crucially, that information isboth material and immaterial." Thisembodied information may arguably becharacterized either as a "law of nature" ora scientific principle, both of which repre-sent exceptions to the categories of patenteligible subject matter according to thestatute. When these laws or principles, i.e.,human DNA or a genetic sequence arepatented, the grantee is given its exclusiveuse, the information is privatized and thepublic's ability to use the informationalcontent is restricted or denied.

This embodied information can simul-taneously be considered to belong to botha part of a body of collective knowledge, i.e.the "human genome," as well as existingwithin any one individual's particular andunique genome, one's own DNA. Thus thepatenting of human DNA and geneticsequences can possibly infringe both anyone individual's First Amendment rights tothe information in the shared humangenome, as well as infringe upon that per-son's ability to have access to theinformation regarding their own geneticprofile.

Benkler's First Amendment concernsregarding the enclosure of information areimplicated as rights inherent in the guar-antees of free speech: the ability tocommunicate or publish "scientific speech"is infringed when the actions or informa-tion necessary for the formulation of thatspeech, the available precursors to speech,are unavailable. This occurs when the rightto gather information necessary for the for-mulation of speech is restricted or denied.Real life implications arise when thisknowledge is unavailable or restricted dueto exclusive or high licensing costs, and thenumerous policy arguments being made inthe Myriad case reveal that harms towomen and public health occur as a result.Innovation and progress in medicalresearch is impeded when researchers areprecluded from using and studying theBRCA 1 and 2 genes. The privatization of

the information and knowledge embodiedby human genes also have "speech costs"and can be seen to threaten the core of ourcivil liberties.

Particular types of patents which aregranted on claims covering methods ofusing genes and genetic information forspecific diagnostic purposes also implicateFirst Amendment guarantees to the pre-cursors necessary for the formulation ofspeech. Drafted to cover the precise func-tions a physician might employ, theseclaims are often written as describing a cor-relation, a relationship between particularDNA or DNA genetic sequence and thepresence or absence of a genetic suscepti-bility to a particular illness or condition.Myriad's method claims to the correlationsinvolving the BRCA 1 and 2 genes and asusceptibility to breast and ovarian cancerare illustrative. When these exclusionarypatents are granted, the ability for others tosimilarly consider the correlation is denied,and the First Amendment guarantee offreedom of thought, fundamental to theability to formulate speech, is infringed.In the coming era of the much discussed"$1000 genome," using such informationaltools, any person wishing to think abouttheir own susceptibility to breast or ovar-ian cancer will be infringing Myriad'spatents when determining if the correla-tion exists in their own body.

The emerging science of epigeneticssuggests that exposure to various environ-ments and personal choices can suppressgene expression, thus affecting and con-tributing to the structure and function ofour personal genomes. This science willhelp to diffuse the problematic political andcultural implications of our human identi-ties, our natures being constructed ordetermined by our DNA, our biology at themolecular level.6 Nonetheless, our ownunique genomes consist of and revealimportant information about ourselves.Thus, per commentator Jonathan Kahn: "Asgenes play an increasingly powerful rolein contemporary legal and political culture,individuals are called upon to refer togenetic information as a basis for assessingtheir rights and duties."7 The plaintiffs andthe ACLU are to be thanked for assertingour Constitutional First Amendment rightsin their case against Myriad Genetics.

Debra Greenfield, JD, is Adjunct AssisstantProfessor at the UCLA Center for Society& Genetics.


A lawsuit brought by the ACLU andallied groups against the U.S. Patent andTrademark Office has challenged thenotion of patents on isolated native DNAsequences. The court's summary judg-ment in favor of the plaintiffs held thatsuch patents covered parts of the naturalworld and were therefore inappropriatesubject matter. The U.S. Department ofJustice has now filed an amicus briefagainst gene patents, but in a morerestricted sense than the original judg-ment. Specifically, manipulations as minoras producing complementary DNA fromthe natural sequence qualify the productas a patentable invention.

What is clear from this is that patentson genetically engineered organisms,which were designated appropriate sub-ject matter under U.S. law by theChakrabarty Supreme Court decision of1980, are unlikely to come under seriouslegal challenge. The position of suchorganisms within the wider culture is alsounassailed given the high penetration ofGM crops in the human and animal foodchains, the extensive use of transgenic

mice-and soon, rats-in biomedicalresearch, and the increasing presence oftransgenic livestock in manufacturing andmeat production operations. Patent pro-tection is just one component of the driveto produce genetically engineered organ-isms, but it represents a strong financialmotivation for (in the words of thephilosopher Francis Bacon) "effecting ofall things possible" in pursuit of utility andprofit.

The cultural currency of transgenicanimals, in particular, and the prospectof more extensive manipulation in thefuture, threatens a number of civilizationalnorms and precepts. In contrast to plants,which in their natural state exhibit wideranging environment-dependent pheno-typic plasticity, animal forms and identitiesare relatively stable, and are icons and con-stants of the visual arts and literature,particularly traditional works and thosemeant for children. Genetic engineeringand other methods of reconfiguring ani-mal biology, such as trans-species cloningand chimerism, inevitably blur the bound-aries between different kinds of organisms,

as well as between organisms and artifacts.Given the phylogenetic continuity of allanimal species, this technology willinescapably come to threaten receivednotions of human uniqueness.

While most members of contemporarysocieties are willing to tolerate, or ignore,the warehousing, instrumentalization andcruelty visited on animals raised for food,research, or other human utility, the priv-ileged status of the human body, even ofthose individuals defined as criminals oroutcasts, has long been normative acrossthe main political and religious spectrums.However, with the rise of religion-basedstates and social movements that deny thehuman value of outsiders, official and pop-ular adherence to a common humanity hasmarkedly weakened over the past decadeeven in modernizing societies commit-ted to classically liberal values. Justificationof torture of suspects by the highest U.S.officials, for example, unwillingness toprosecute its perpetrators or those per-forming grievous acts against bystandersin targeted groups, and nonchalance of thepublic about military methods guaranteed


Patents on Genes, Organisms - and Human(oid)s?Life patents go far beyond genes - but just how far remains to be seen

BY STUART NEWMAN

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Synthetic biology -the design and con-struction of new biological parts, devicesand systems that do not exist in the natu-ral world and the redesigning of existingbiological systems to perform specifictasks-will bring the next wave of patentson living organisms. Synthetic biology notonly poses new challenges to biosafety andbiosecurity but also to our patent system.Discussions on gene patents must includesynthesized DNA lest technology againjumps ahead of our patent system and wespend decades trying to play catch-up.

Instead of inserting genes from onespecies into another, what is considered"traditional" genetic engineering, syntheticbiologists claim that they aim to "create"life from scratch with computer-synthe-sized DNA or without the use of DNAentirely. Much of what is called "syntheticbiology," however, does not achieve thislevel of change.

Nonetheless, in May 2010 J. Craig Ven-ter and his team announced they had"created" the world's first organism witha synthetic genome. The success of Ven-ter's team may be more in the area ofpatents that will apply to his new tech-niques than in actually having "created"synthetic life.

Dr. David Baltimore, a leading geneti-cist at Caltech, described the work to theNew York Times as "a technical tour deforce" but not breakthrough science, butjust a matter of scale … He has not createdlife, only mimicked it."

The Venter team could not get the cellto reproduce without placing the syntheticgenome in a preexisting cell, which was

naturally inclined to make sense of thetransplanted DNA and to turn genes onand off. In effect, the bacteria did whatthey have done for eons: swap DNA.

Still, this was the first time much of thepublic had heard of synthetic biology andwas a wake-up call to many that currentregulations around biotechnology arealready outdated. Unfortunately, whileVenter's team may have only copied thegenome of a goat pathogen, their intel-lectual tour de force includes patentingeach of the steps in the process that theyused to make the copy. Nobel Prize win-ner, John Sulston, has argued that Venteris interested primarily in patenting theprocess to exclude 'free research' by oth-ers.

In 1980, the Supreme Court ruled inDiamond v. Chakrabarty that geneticallyengineered life forms could be patented.The case was referring to more traditional

genetic engineering (in this case,bacterium that was engineeredto eat crude oil), but the court'sruling will undoubtedly beextended to the products of syn-thetic biology. The ruling states"…the patentee has produced anew bacterium with markedly dif-ferent characteristics from anyfound in nature and one having

the potential for significant utility. His dis-covery is not nature's handiwork, but hisown: accordingly it is patentable subjectmatter."[4] Venter's inclusion of additionalDNA to mark the synthetic genome ashis own is an additional step that makesclear that his 'invention' does not exist innature.

Since then patents on naturally occur-ring genes and DNA sequences have beengranted, despite the Court's clear messagethat naturally occurring DNA is notpatentable. Currently, over 20% of thehuman genome has been patented as wellas thousands of plant, animal, virus, andbacteria DNA sequences that have natu-rally evolved over billions of years but were


Synthetic Biology - The Next Wave ofPatents on LifeNot only can synthetically engineered organisms be patented -so can the processes used to create them

BY ERIC HOFFMAN AND JAYDEE HANSON

to kill civilians and noncombatants (incontrast, for example, to the Vietnam warera), have risen in concert with the inno-vations in the murderous tactics of theU.S.'s opponents.

It might seem incidental that this starkchange in attitude (extending across theconservative-liberal and religious-seculardivides) toward the bodily integrity ofthose defined as "other" has come aboutsimultaneously with the capability togenetically engineer animals, including(absent some loose and internationallynonuniform legal prohibitions) humans.But the following contemporaneoustrends should also be considered by wayof context: (i) an ageing population in theU.S. and elsewhere, in need of spare bodyparts, is creating a demand for tissues andorgans the provision of which will onlyoccur under patent protection; (ii) suchrepair tissues and organs will be most use-ful if their sources are close to human,but most patentable if they are not exactlyhuman; (iii) "reprogenetic" technologynow permits production of human, orhumanoid, individuals from stem cellsderived from anonymous discarded tissuesrather than any parent-associatedembryos; (iv) for genetically modifiedorganisms of human origin, the preciseboundary between non-human andhuman is no less socially constructed thanis the boundary between "us" and "them"in the political realm.

It is difficult to avoid the conclusionthat as medicine becomes increasinglyhigh-tech and personalized for those whocan afford it, and the disparity in nationalwealth and income remains at its recordlevels in the U.S., there will be scientificand economic incentives to produce near-humans for research and therapy. Thedecline in the allegiance to a notion ofhuman social commonality, along with therise in the scientific understanding ofhuman biological commonality and themeans to manipulate and exploit itthrough, among other things, patent pro-tection of genetically modified animals,seems to be an explosive combination.

Stuart A. Newman, PhD, is Professor ofCell Biology and Anatomy at New YorkMedical College and former member ofCRG’s Board of Directors.

At stake is whether the knowledgeof how life works at its most basiclevel should be a common propertyof all, or whether it should be controlled by a few.

pulled out of the commons into privatehands through patents and intellectualproperty rights. The U.S. Patent andTrademark Office currently argues thatthe mere act of "isolating" DNA is aninventive step worthy of a patent. Whilethe Department of Justice has argued in abrief to the court that merely isolatingDNA is not sufficient for a patent, the Ven-ter team's work goes beyond isolatingDNA to actually writing the sequence andgetting it to "boot up" (their words!).

Now, with synthetic biology, mere "iso-lating" is not even necessary. One couldtheoretically upload a DNA sequence ontoa computer, "print out" an exact copy ofthat DNA sequence, and patent thesynthetic DNA sequence as aninvention. Less theoretical-and withmany more commercial applica-tions-is creating copies of naturalDNA and making slight tweaks tothe genome as the inventive stepworthy of a patent. In effect, syn-thetic biologists are able to "evolve"organisms through computer algo-rithms and create novel DNAsequences that can be then be"printed" out and inserted into anorganism.

Patents have already beengranted on many of the processesand products involved in syntheticbiology, including patents on meth-ods for building synthetic DNA,synthetic genes and DNAsequences, synthetic pathways, syn-thetic proteins and amino acids, and novelnucleotides that replace the letters ofDNA.

For example, in 2007 the J. Craig Ven-ter Institute applied for a frighteninglybroad patent of its "minimal bacterialgenome" called Mycoplasma laborato-rium. This organism was an attempt tocreate life with the minimum number ofgenes by cutting out as many DNAsequences as possible without removingits ability to reproduce or survive. U.S.patent numbers US2007 0264688 andUS2007 0269862 describes creation of thefirst-ever, entirely synthetic living organ-ism-a novel bacterium whose entiregenetic information is constructed fromsynthesized DNA (but whose genome isa near-replica of a naturally occurringgenome).

This patent claims exclusive monop-oly on the genes in the minimal bacterialgenome, the entire organism made fromthese genes, a digital version of the organ-

ism's genome, any version of that organ-ism that could make fuels such as ethanolor hydrogen, any method of producingthose fuels that uses the organism, theprocess of testing a gene's function byinserting other genes into the syntheticorganism, and a set of non-essential genes.These patents are not restricted to anyspecific cell type-it currently applies toprokaryotes and eukaryotes - or size of asynthetic genome.

While these patents have yet to begranted, the claim shows the extent towhich some synthetic biologists are test-ing the limits in the battle to control thefundamental building blocks of life and

actual living organisms. While it is likelythis specific patent application's scope willbe limited to cover only bacterial cells,such a patent would still grant Venter andcompany an exclusive license to createsynthetic fuel-producing bacteria and thetools to create such organisms. Conve-niently, Venter's company, SyntheticGenomics, has contracts with both ExxonMobile and BP to produce "next-genera-tion" biofuels from synthetic cells (or atleast genetically engineered cells that con-tain synthetic DNA sequences).

Amyris Biotechnologies is a syntheticbiology company that used geneticallyengineered yeasts that contain syntheticDNA to break down sugarcane to produceisoprenoids–which are then being con-verted to biofuels, industrial chemicals,among other products. Patent US7,659,097, granted to Amyris in February2010, covers the production of many dif-ferent isoprenoids created though anumber of different microbes. Amyris

already has deals with major oil and chem-ical companies to turn Brazilian sugarcaneinto high-value commodities. Again,Amyris' "biosynthetic pathways" are near-copies of metabolic pathways found innature with some "tweaking" of the DNApathways to allow the yeast to do somethings that traditional genetic engineeringcould not accomplish.

The novel challenge created by theemerging field of synthetic biology is thatnot only can natural or synthesized DNAbe patented, but the processes used to syn-thesize DNA and create syntheticorganisms can also be patented. Further-more, the living organisms created with

synthetic DNA are covered inthese patents, as are the productsthey are engineered to produce.

Take Amyris as an exampleagain. Through their patent, theyown the process of engineeringmicrobes with their syntheticDNA, the synthetic DNA, themicrobes themselves, and anyproducts the microbes produce. Ifthese microbes escape and con-taminate wild-type relatives, theirsynthetic DNA could pass on andAmyris would theoretically ownthose new microbes that havebeen contaminated with syntheticDNA.

There is a significant battlegoing on here. At stake is whetherthe knowledge of how life works atits most basic level should be a

common property of all, or whether itshould be controlled by a few. This is noth-ing short of intent to further own andcontrol the building blocks of life.

What must be doneWhile it is clear to us that current court

rulings would likely support the patentingof synthetic genomes as developed by Ven-ter's lab and other researchers, Congressshould prevent the patenting of DNAsequences that simply copy naturallyoccurring DNA. To do otherwise would ineffect allow another way to patent natu-ral occurring organisms and theirDNA-just make synthetic copies of them.That is in no one's interest but the patentholders’.

Eric Hoffman is Biotechnology PolicyCampaigner with Friends of the EarthU.S.Jaydee Hanson is Policy Director withthe International Center for TechnologyAssessment


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The Equal Employment OpportunityCommission recently issued its Final Ruleimplementing the Genetic InformationNondiscrimination Act after beinggranted broad authority to interpret it bythe United States Congress. In it, theEEOC laid out in detail strong protectionsagainst genetic discrimination andemployer access to genetic information forevery American worker.

The Council for Responsible Genet-ics played the lead role in advocating fora strong Final Rule implementing GINA.We met multiple times with the EEOCCommissioners and formally testifiedbefore them. CRG was the lead drafter ofmultiple sets of written comments in con-junction with the Genetics and PublicPolicy Center-comments that wereadopted by civil rights and patient'sgroups, including the Leadership Con-ference on Civil Rights, American CivilLiberties Union, Genetic Alliance and theCoalition for Genetic Fairness. This wasa significant victory for the Council forResponsible Genetics, as virtually all ourrecommendations for reform were incor-porated by the EEOC into the Final Rule.

As a result, the EEOC's Final Rule nowincludes:

- strong and unambiguous definitionsof key terms

- narrowly crafted exceptions to therule against acquisition of geneticinformation

- clarification of the relationshipbetween GINA and other civil rightsand consumer laws in a mannerthat benefits the employee/con-sumer. With regards to definitions, we were

able to persuade the EEOC to include inthe Final Rule an expanded and clarifieddefinition of "genetic test" to ensure car-rier screening for adults, newbornscreening, ancestry and paternity testingetc. were formally acknowledged in thedefinitions.

We were also able to persuade them toclarify the definition of "manifested dis-

ease" so that individuals whose diagnosiswas principally based on genetic informa-tion would remain protected by the lawand that individuals who had manifesteda genetically based disease continued tohave their genetic information protected.

With regards to the prohibitions on"requesting, requiring, or purchasing"genetic information, the EEOC formallyacknowledged our interpretation thatGINA does not require that "intent" bepresent for a violation of GINA to occur.

The EEOC also adopted our interpre-tation that the exceptions to this ruleshould be narrowly construed. For exam-ple, they agreed that employers who mightstart with an innocent question, such as"How are you?," could not then follow upwith more probing questions that mightelicit genetic information. They furtheradopted our suggestion that employerswho request medical information gener-ally, under any circumstance, mustindicate to whomever they ask that theydo not want genetic information (a formalsafe haven) to limit the opportunities forreceiving genetic information as part ofthe normal course of business.

Wellness programs that include healthrisk assessments or require "qualification"to participate in a specific program areripe for access to genetic information. Ouradopted comments now ensure that pro-vision of such information must becompletely voluntary and that no financialincentives can be offered. Furthermore,individuals who do not wish to providetheir genetic information must be allowedalternative ways to qualify for participa-tion in tailored programs.

GINA makes an exception for theacquisition of genetic information fromcommercially and publicly availablesources, such as picking up the newspaperand reading in the obituaries that anemployee's parent died of a hereditarycondition. The exception specificallyexempts medical databases and courtrecords. We argued that this provision wasnot meant to protect someone who was

either intentionally looking for geneticinformation (even in open sources such asperiodicals) or someone who was look-ing in any source that provided aheightened risk of obtaining genetic infor-mation. The EEOC agreed and includedthese distinctions in the Final Rule, as wellas extending them to online sources.

Many additional interpretations ofours were included in the Final Rule,including a clarification of the interac-tion between the health insurance andemployment sections of GINA in a man-ner that benefits the employee/consumerand ensures they are implemented andenforced with consistency and clarity.

Finally, our comments suggested thatthe Commission include specific examplesthroughout the Rule to illustrate itsbreadth. The Commission went to greatpains to do so, and included several ofour sample scenarios.

GINA now provides strong new pro-tections for all Americans againstdiscrimination and access to genetic infor-mation. As a result, Americans can finallytake advantage of the tremendous poten-tial of genetic research without the fearthat their own genetic information willbe used against them. While there is stillmuch to do to ensure that genetic privacyin this country is respected, we are onestep closer to our goal.

The Final Rule implementing GINAmay be accessed in the Federal Registerhere:http://frwebgate2.access.gpo.gov/cgi-bin/PDFgate.cgi?WAISdocID=iAu91C/0/2/0&WAISaction=retrieve

Jeremy Gruber, JD, is President and Exec-utive Director of CRG.


EEOC Issues Strong Final Rule Implementing GINAThe Genetic Information Nondiscrimination Act will provide strong new protections against genetic discrimination

BY JEREMY GRUBER

Historically, manipulation of women'sbodies by others for profit has taken manyforms. One such practice with a long andtragic history is the overzealous prescrib-ing of synthetic hormones. Defined astreatments, rather than experiments, thefirst synthetic hormone, diethylstilbestrol(DES), and post-menopausal hormonereplacement therapy were prescribed towomen for decades before their deadlyside effects were documented and theiruse finally curtailed. A current form ofhormone abuse encourages financiallystrapped college students to "donate" theireggs by offering thousands of dollars andskillful appeals to their altruism. Now,biotech entrepreneurs are partnering withfertility clinics in hopes of acquiring eggsfor research cloning, making oocytes aneven more highly coveted naturalresource. Are we repeating a historical pat-tern in which the casualties from medicalmisuse of hormones must reach epidemicproportions before the damage they causeis officially acknowledged?

In this article I will briefly reviewknown short-term risks and the morepoorly understood long-term risks of eggdonation. I will describe some of theefforts that have been made to increase theintegrity of the currently empty ritual of"informed consent" by which this expand-ing trade is being justified. I will concludeby considering some implications of thegrowing trade in human eggs.

A Few of the CasualtiesCalla Papademous answered an ad in

the Stanford University newspaper prom-ising $50,000 to a tall, athletic youngwoman with an SAT score over 1400.1Thinking she had found a way to repaysome of her student loans she answeredthe ad and was accepted. After only a fewdays on Lupron, commonly prescribed foregg donation but unapproved by the FDAfor this purpose, she suffered a massivestroke. Today, after extensive therapy, sheis rebuilding her life, but still suffers somepermanent brain damage, physical disabil-ity, and is infertile. Since she failed to

produce the eggs she was offered only$750.

Alexandra X., featured in the docu-mentary Eggsploitation, was a graduatestudent in need of money to pay expenseswhile finishing her dissertation in biology.She was happy to receive $3,000, andthought she had successfully completedthe process only to collapse in pain onthe floor of a friend's house eight or ninedays after the retrieval. After fertility clinicstaff where her eggs had been removedrepeatedly dismissed her symptoms as"normal," she was finally hospitalized withinternal bleeding and rushed into surgeryjust in time to save her life, but only one ofher ovaries. Five years later, in her earlythirties, with no family history of the dis-ease, she was diagnosed with stage 2-Bbreast cancer.

Deaths from early-onset reproductiveand other cancers have been documentedin a number of former egg donors and inmany women who have undergone essen-tially the same ovarian hyperstimulationand egg retrieval as part of their own invitro fertilization. Consider Stanford stu-dent Jessica Wing, who was stricken withfatal colon cancer shortly after her thirdegg retrieval and died at age 32. Her physi-cian mother, Jennifer Schneider, hadgenetic tests conducted, which ruled outany genetic susceptibility to the disease.Based on this and further research into theissue, she has challenged the adequacy ofcurrent standards of informed consent andhas become an advocate for betterprospective studies of egg donors.2

Just how common are tragedies suchas those described above? No one knows.We cannot be sure that early onset can-cers, such as Jessica Wing's, are related toearlier ovarian stimulation. Nor can we besure they are not caused by the radical dis-ruption of the endocrine system thatcharacterizes typical egg harvesting pro-tocols-no one is keeping track of eggdonors once they leave the clinics.

What we do know is that the Ameri-can Society of Reproductive Medicineacknowledges significant risks in its pro-

fessional literature. Its Ethics Committeestates that donors are "exposed to risks ofmorbidity and a remote risk of mortalityfrom COS [controlled ovarian stimulation]and oocyte retrieval" and that "it is possi-ble that fertility drugs could increase awoman's future health risks, including therisk of impaired fertility."3 We also knowthat an unknown number of women havedied during the development and applica-tion of these practices,4 which have nowbeen refined to the point that fatalitiesappear to be rare. But then again, no oneis counting.

How invasive is the process?In 2006, the California Institute of

Regenerative Medicine asked the Instituteof Medicine to convene a conference toprovide information on the safety of eggdonation. The conference report, “Assess-ing the Medical Risks of Oocyte DonationFor Stem Cell Research,” draws on stud-


Dangerous HarvestEgg donation includes many known short-term risks and lessoften discussed long-term risks

BY DIANE BEESON

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ies of women undergoing ovarian stimu-lation to extract eggs for their own fertilitytreatment, and describes the process thisway:

The woman self-injects hormones(gonadotropins) to stimulate thegrowth of ovarian follicles, plus agonadotropin-releasing hormone(GnRH) agonist to block the normalsurge of lutenizing hormone (LH),which could cause the woman to ovu-late before the physician retrieves theeggs. . . . A woman subsequently self-injects the hormone human chorionicgonadotropin (hCG, similar to LH) toeffect egg maturation. When the eggsare ready the woman is brought intosurgery, where she receives intra-venous sedation, after which atransvaginal probe is placed in hervagina. A hollow needle emerges fromthe probe, travels through the back ofthe vagina and into the ovary, whereunder the guidance of ultrasound tech-nology, the eggs are aspirated.5

What are the short-term risks?The ingestion of various drugs in

preparation for egg retrieval, and the eggretrieval process itself, entail a variety ofphysical and psychological risks, includ-ing those stemming from the use ofanesthesia, and surgical complicationssuch as infection and bleeding. The mostcommon side effect connected with eggdonation is ovarian hyperstimulation syn-drome, or OHSS. This may includenausea/vomiting, pain, fluid buildup in theabdomen, shortness of breath, and in moreserious cases, blood clots, severe pul-monary distress, and kidney (and/or otherorgan) failure.6

The IOM report cites three prospec-tive studies on women undergoing fertilitytreatment that estimate the risk for OHSSto range from 2.1 to 4.7 percent.7 At thesame time, it acknowledges both that "thedata concerning the occurrence of ovar-ian hyperstimuation syndrome are notparticularly good"8 and that the definitionof this iatrogenic disorder has been redefined to exclude its mildest manifes-tations.9

More recently, a non-industry-spon-sored retrospective report of 155 formeregg donors found that over 30% reportedsome degree of OHSS, and 11.6% requiredhospitalization and/or paracentesis (punc-turing of the belly with a needle to drawout fluid), revealing a striking discrepancybetween risk rates reported by industry

insiders and independent researchers.10

What are the long-term risks?Less well understood, but of even

greater concern to women's health advo-cates than the short-term effects, are thelong-term risks, particularly reproductivecancers. The IOM Report dismisses evi-dence of increased risks for breast,endometrial, and ovarian cancers found insome studies, but acknowledges concernwith regard to uterine cancer. It alsoacknowledges that the studies that foundno increase in risk may have done so dueto inadequate long-term follow-up.11

The IOM Report concludes by admit-ting that "one of the most striking facts"about ovarian stimulation is how little isknown about its long-term effects onwomen:

Although more than a million IVFcycles have been performed in theUnited States over the past 20 years…there are no registries that track thehealth of the people who have takenpart. …[T]he studies vary quite a lotin terms of study design, the numberof subjects, and outcome, so it isimpossible to draw a consistent picturefrom them.12

In the four years since the IOM con-ference was held concerns regardingcancer as a potential long-term side effectcontinue to mount. According to Dr.Louise Brinton of the National CancerInstitute:

There has been little attentionfocused on the long-term effects ofassisted reproductive technologies,which often involve much higher expo-sures to gonadotrophins than werereceived by women in previous eras. .. . Since in-vitro techniques havebecome common only in the last cou-ple of decades, it may be some timebefore epidemiological studies canamass the follow-up times requiredto fully address long-term effects.13

She also states:Although most attention has focusedon effects of fertility drugs on ovariancancer risk, more recent investigationssupport the need for further attentionon breast and endometrial cancers.The need is supported by the recog-nition that ovulation-stimulating drugsare effective at increasing both oestro-gen and progestin concentrations,alterations that have been linked with

both of these cancers. Further, a rela-tionship with breast cancer wouldparallel findings of an increased risk ofthis tumor among mothers exposed todiethylstilbestrol during pregnancy.14

While Brinton links ovarian stimula-tion to the DES disaster, prospective eggdonors are not likely to know that it tooknearly three decades of exposure to thisfirst synthetic hormone before its causallink to elevated cancer rates among boththe women to whom it was prescribed andtheir daughters, and genital abnormalitiesin many of the sons was documented.15Ironically, exposure to DES in utero is aknown cause of infertility in females, thuscontributing to the market for today's fer-tility industry. In the case ofpost-menopausal hormone therapy, it wasonly after decades of demands fromwomen's health advocates that clinical tri-als belatedly were begun. These trials werestopped in 2002 when it became appar-ent that women taking estrogen plusprogestin were having more strokes, heartdisease, and breast cancer.16 The follow-ing year, when tens of thousands of womenstopped taking these hormones, we wit-nessed an unprecedented decrease in newcases of breast cancer.17

Brinton is not the only epidemiolo-gist with concerns about ovarianstimulation. A recent Israeli study found"an association between treatment forovulation induction and overall risk ofcancer, particularly cancer of theuterus."18 But cancers are not the onlypoorly documented risk. Both cerebral19and myocardial infarction,20 for example,have been reported in women undergoingovarian stimulation even in the absence ofOHSS. Egg donors interviewed by thisauthor report ovarian cysts, severe moodswings, uncontrollable weight gain, andnumerous other life-disrupting symptomsthat are ignored in the existing researchand were not considered in the IOMreport.

The lack of adequate longitudinal datameans that "informed consent" functionsprimarily to protect clinics and profession-als from liability, but fails to meaningfullyprotect egg donors. Ads focusing on finan-cial compensation and altruism, to theexclusion of any suggestion of possiblerisk, have created a culture on college cam-puses in which it is widely believed is thategg donation is well established, routine,and completely safe. Furthermore, consentforms, whatever their content, are notlikely to be seen by potential donors until


long after they have made the decision,based on ubiquitous advertising, to selltheir eggs. Alliance for Humane Biotech-nology activists last year succeeded ingetting support for AB 1317, a bill in theCalifornia legislature, to require that adssoliciting egg donors reference existenceof medical risk, but the American Soci-ety of Reproductive Medicine insisted thatthe bill exempt brokers and clinics whoagree to follow ASRM ethical guidelines.The result? Egg broker ads referencinghealth risks have yet to be spotted.

Two recent studies, one of advertisingand compensation for egg donors, theother a study of compliance and range offees among egg donor and surrogacy agen-cies, both found that many of the eggdonor agencies in the U.S. routinely vio-late ASRM's ethical guidelines.Compliance, to the extent it does exist, isself-reported and unverified. The guide-line's primary function seems to be tosupport claims of self-regulation.

Women having their eggs harvested fortheir own use in the hopes of achievingpregnancy face essentially the same risksfrom ovarian stimulation as egg donors.The justification for the risk in their caseis the hoped-for birth of a child. How-ever, concerns acknowledged by 2010Nobel Laureate R.G. Edwards about safetyand damage that routine IVF may cause toboth infertility patients and offspring arefueling international interest in alternativefertility treatments such as minimal stim-ulation IVF and natural cycle IVF.21

Scientists push for easier access to eggsIn discussing scientists' interest in

acquiring eggs for cloning research, theauthor of a 2006 Nature article acknowl-edged that "cloning is a wildly inefficientprocess" and that egg donations are "anethical quagmire."22 Long before thedemand for eggs reached this point, in2001, pro-choice women's health advo-cates, led by Our Bodies Ourselves,sponsored a call for a moratorium onembryo cloning primarily because of itsdependence on large numbers of humaneggs.23 Three years later Korean stem cellresearcher Hwang Woo-suk was foundto have used more than 2,200 eggs in hisfraudulent effort to harvest stem cells froma cloned embryo. This resulted in 17.7 per-cent of the women who supplied the eggssuffering adverse health effects. Chargesof coercion and human rights violationsensued.24

The large number of human eggs

required for cloning research was a driv-ing concern for pro-choice feminists whoopposed California's 2004 $3 billion ini-tiative that established the CaliforniaInstitute of Regenerative Medicine.Alarmed at the bill's prioritization ofresearch cloning, a process dependent onwomen's eggs, a group of women's healthadvocates, this author included, formedthe ProChoice Alliance Against Proposi-tion 71. We submitted for inclusion in theVoter's Handbook a statement arguingagainst the measure. Proponents of the ini-tiative, including two prominent scientists(one a Nobel laureate), then took legalaction in an unsuccessful attempt to keepus from both using the word "cloning" andfrom relating to voters that embryocloning relies on a large supply of humaneggs.25 Today, scientists are protectedfrom acknowledging that egg harvestingexposes women to significant risks by thefact that the research necessary to deter-mine the extent of the harm has yet to bedone.

A series of international and nationaldeclarations and regulations affirm theimportance of informed consent and theprohibition of undue inducement or influ-ence. Disregarding these principles isconsidered a violation of human rights.These international standards inform theNational Academy of Science's guidelinesrecommending that "[n]o payments, cashor in kind, should be provided for donat-ing oocytes for research purposes."26Nevertheless, in 2009 New York becamethe first state to disregard the NAS guide-lines. At a hearing of the state's EthicsCommittee to consider the ethics of pay-ment, physician Jennifer Schneiderdescribed her daughter's tragic prematuredeath following her third egg donation.She challenged the committee: if it choseto ignore NAS Guidelines, would it at leastrecommend the establishment of a donorregistry to facilitate monitoring the long-term effects of egg donation?27 Thecommittee made no such recommenda-tion.

In 2006, the ProChoice Alliance forResponsible Research led a successfuleffort to pass California law SB 1260,which tightened restrictions on compen-sation for eggs (beyond expenses) fornon-CIRM-funded research and closed aloophole in CIRM's regulations that couldhave allowed the use of non-CIRM moneyto acquire eggs. Since then, CIRM Direc-tor Alan Trounsen has made it clear hehopes to change this.28 In June of this year

CIRM held a workshop in which legal andethical obstacles to achieving Somatic CellNuclear Transfer were discussed. Thepublic was excluded from this workshop,in what one commentator called an appar-ent violation of the "the spirit and probablythe letter of the California State Consti-tution and state open meeting laws."29Minutes of this meeting make it clear thatdespite acknowledging medical and ethi-cal barriers to procuring eggs from humandonors through ovarian stimulation, manyscientists are intent on pursuing researchusing human eggs.30 And most recentlya lobbyist for the American Society ofReproductive Medicine volunteered thatthe ASRM was considering sponsoringlegislative changes to remove prohibitionson payment for eggs for research in Cali-fornia.31

One of the implications of the expan-sion of the egg trade to procure eggs forresearch is that, unlike the eggs sought forreproduction, the genotype of the donoris usually irrelevant. This means the mar-ket can be expected to move beyondcollege campuses and into the poorestcommunities, both in the US and aroundthe globe, where financial inducementsmay be even more irresistible and socialconditions may further compromise theintegrity of these transactions.

Alliance for Humane Biotechnology isone of several organizations attempting toalert the public and policy makers of therisks to which egg donors are beingexposed. Earlier this year AHB was con-tacted by a young man worried about hisgirlfriend who, after donating eggs, suf-fered a seizure, mood swings, shortness ofbreath, and blurred vision. He wantedadvice on what she should do-having nomedical insurance and a denial from theclinic that her symptoms were caused bythe egg harvesting. While examples ofcasualties abound, those profiting fromthe practice of egg donation continue todismiss the accounts as anecdotal. Thiswill likely continue until an independentnational registry of women undergoingovarian stimulation is established andadherence to ethical standards is enforcedby independent oversight.

Diane Beeson, PhD, is chair of the Depart-ment of Sociology and Social Services atCalifornia State University, East Bay.

Acknowledgement: The author isindebted to Tina Stevens for a close read-ing, helpful suggestions, and generouseditorial assistance.


Women's inferior status throughoutthe world renders them more exposedthan men to poverty, gender-basedexploitation and all forms of trafficking.One of the newest forms of trafficking hasemerged as a result of exponential growthin the worldwide use of new reproduc-tive technologies. The internationalcommunity faces a reality in which med-ical knowledge and technologies that weredeveloped for healing purposes are usednot for saving lives, but rather for allow-ing people with economic means to fulfilla very specific kind of parenthood thatoften exploits the economic distress andrisks the health of certain other women.This situation causes great concern amongfeminists, as transnational surrogacy andthe trade in human eggs have become per-vasive international phenomena.

Mediating agencies use various inter-national trade routes to connect doctors,parents-to-be, and women willing to selltheir eggs or rent their wombs.

Ova trade: Would-be parents oftentravel from western countries such as theUSA, Germany, the U.K and Israel to East-ern Europe, India, Cyprus and othercountries where payment for ova ischeaper or not legally regulated as it is intheir home countries. In countries whereova sale is prohibited, hormones may beadministered in the home country to thewomen who are then flown to a secondcountry where their eggs are harvested,fertilized and inserted in the receivingwoman's uterus. Many significant short-term health risks to women are incurredin the process of extracting abnormallylarge numbers of eggs from their ovariesper a single cycle. Long-term effects are

less well understood but are known toinclude infertility and possibly reproduc-tive and other cancers. Inadequate longterm research has been conducted onthese health risks. (See the accompany-ing article in this issue by Diane Beesonfor more detail.)

Surrogacy trade: Fertilized eggs oftentravel across international borders, some-times arriving from one country while thesperm arrives from another country. Thefertilized eggs may be passed to a thirdcountry where the woman who willbecome the surrogate mother resides andwhere the procedure of the insertion intothe uterus is performed. Great concernregarding human rights violations result-ing from the exploitation of low incomeand poor women, along with the absenceof truly informed consent, is growingamong advocates and many fear that thesituation resembles trafficking in organssuch as kidneys.

These procedures frequently involvethe administration of synthetic hormonesinjected to produce abnormal numbers ofeggs. As a result, when a pregnancy is suc-cessfully produced, it often consists ofmultiple embryos. The surrogate is thensubjected to much higher levels of riskthan a normal single pregnancy involves.Post-natal health care costs for treatmentof complications are often not covered.Furthermore, the costs of health care pro-vided to infants born with congenitalproblems may not be claimed by theintended parents. A typical situation is thecase of the surrogate mother who waspressured to have an abortion after thefetus she was carrying failed to meet thequality specifications of those who hired

her when they were informed that thefetus had Down Syndrome.1 Surrogatetransactions are often facilitated by entre-preneurs operating without supervision ormonitoring of women's health, and withlittle apparent concern about protectingsurrogates from exploitation or criminalabuse.

In 2009, what is known as the "Roman-ian scandal" was exposed. Israeli doctorswere involved in the trafficking of eggs ofyoung poor women at SABYC clinic inRomania, some of whom were only 15years old, with little understanding of thehealth risks involved. In one example, a 16-year-old factory worker was left in criticalcondition after the procedure. The arrestof the doctors and agency operators byRomanian police revealed the ways theinternational reproductive industry isworking as a free zone with no ethics orresponsibility for respecting human rightsor human dignity.2

Information on the magnitude of inter-national trafficking in reproductive organsis scarce and partial, rendering many ques-tions unanswered. Of particular interest isinformation regarding the health andsocial repercussions of this industry onwomen, and the economic gains of the var-ious players in this field.

While there is legislation of varyingdegrees among different countries, rang-ing from full prohibition of egg donationand surrogacy to weak attempts at regu-lating aspects of this reproductive trade,the gaps are enormous and the industrymetastasizes largely without any account-ability. Such laws as exist are implementedsolely at the national level.

The phenomenon of trafficking is notlimited to countries that lack regulation.


Reproductive Trafficking

A global women’s human rights issueBY HEDVA EYAL .

Black markets are known to developalongside the publicly authorized services,offering leniencies that give them advan-tages from the buyers' point of view.Within this market, many grey areasremain. For example, in Israel, youngwomen may receive hormonal treatmentsto stimulate egg production legally, whilethe harvesting takes place illegally outsideof the country.

The transnational nature of reproduc-tive trafficking means that activism at thelocal level to reduce it is not enough. Inlight of these realities, women's healthadvocates have begun an international ini-tiative to address the increasing problemof reproductive exploitation and commod-ification. Over the past year, action hasbegun to draft a call for a UN declarationon human rights abuses in reproduction.

Documents that should inform such adeclaration include the Nuremburg Code(1947)3 on human experimentation; theWorld Health Organization's Draft Guid-ing Principles on Human OrganTransplantation (1991) and its Commen-taries;4 the European Convention onHuman Rights and Biomedicine (1997)5and its Additional Protocol on Transplan-tation of Organs and Tissues of HumanOrigin (2002);6 and the Helsinki Decla-ration (Sixth Revision 2008) on humanexperimentation.7 Although these docu-ments more specifically pertain to humanexperimentation and organ transplanta-tion, in some cases even deliberatelyexcluding reproductive tissues includingova, they can be applied to reproductiveorgans and tissues as in the case of theDraft Guiding Principles on HumanOrgan Transplantation of 1991.8

Universal legal agreements on the traf-ficking of ova and surrogacy shouldprotect the basic rights and interests ofwomen, which form part of the set oflegally binding obligations on countriesthat have agreed to these treaties. An inter-national regulation might offer a basis fordetermining when eggs are being traf-ficked. It could also determine whatprecautions every country should takewithin its boundaries in order to protectall women concerned.9 For example, theEuropean Committee's 2004 resolutioncondemns any trade in human tissues andplaces crucial importance on encourag-ing EU members to incorporate in theirlaws the principal of voluntary donation(see clauses 14 (2) 12(1)). Furthermore, theresolution mentions the need for creat-ing a monitoring mechanism on import

and export that will take into account boththe protection of donors and the quality oforgans and tissues (clause 9).10

The practices of reproductive organ,tissue and cell trafficking and trade, par-ticularly ova sale and surrogacy, infringeupon several basic human rights underinternational law and are violations ofinternational agreements on health andmedical standards. Trade in reproductivesurrogacy, organs and tissue must be rec-ognized as a unique kind of humanexploitation.

The absence of an international stanceon reproductive trade allows the free mar-ket to set the standard for using and sellinghuman organs, including reproductiveorgans, cells and tissue. Medical technolo-gies become a tool for people who, in thename of creating or saving life, are usingwomen as objects of human organ stock.

It is our belief that taking a feministstance on this issue will be beneficial forwomen throughout the world. There mustbe an international platform for discus-sion. The field of reproductivetechnologies raises complicated issuesregarding autonomy and commodificationof women's bodies, the medicalization ofwomen, trafficking, children's rights, anda plethora of other issues. Alongside thesequestions are another set of issues regard-ing the right course of action. Couldinternational regulation protect women orsimply achieve legitimization of reproduc-tive trade? Although there is awarenessof these questions, recognition of the legit-imacy of the fertility-industrial complexand its practices affects women's rightsand health negatively. Recognizing theproblem and bringing these issues to theforefront of the international agenda is thecrucial first step. The need to convenean international meeting of women'shealth and human rights advocates todevelop a universal feminist stance on theissue of reproductive trade is urgent.

The opportunities that these medicaltechnologies provide also require that weface the question of who truly is paying theprice. The obligation of each one of us isto acknowledge the irrelevance of nationalborders concerning this issue and to focuson the abuses occurring and to developprotective measures that will ensure thehealth and safety of women throughoutthe world.

Several elements provide a frameworkfor the creation of an international decla-ration on human rights abuses in humanreproduction that protects the rights and

health of women and the children towhom they give birth:

- The commercial use of women's repro-ductive capabilities both within andacross national borders should be pro-hibited.

- Surrogates and ova donors should berecognized as human participants ina complex birth-giving process, ratherthan as biological resources. Conse-quently, practices that bar humancontact between surrogates, eggproviders, and the children bornthrough these processes should bestrictly prohibited.

- Surrogacy and egg donation shouldbe permitted only under circum-stances allowing for the viablepossibility of a prolonged relationshipbetween and/or among surrogate,gamete donor, child, and growing fam-ily.

- All medical procedures must be con-ducted within the country of origin ofthe intended parent(s) by legallyauthorized fertility experts in licensedhospitals and/or clinics.

- Recipients of fertility treatment hor-mones of any kind must be informedthat past uses of synthetic hormoneshave led to significant increases in can-cer rates among women to whom theywere prescribed, and that the long-term medical risks of hormonescurrently used in fertility treatment(often unapproved for this purpose)are unknown due to a dearth of long-term studies of the effects of thesedrugs on recipients. The hope is that these elements will be

a basis for international dialogue betweenwomen and organizations that address theincreasing problem of reproductive organtrade and trafficking. We have seen theeffects of these phenomena on women'slives, and we are asking the internationalcommunity to take social responsibilityand actively defend human rights.

Hedva Eyal, is Women & Medical Tech-nologies Project Coordinator with IshaL'Isha (Woman to Woman) Haifa FeministCenter, Israel.

Editorial assistant: Kathleen Sloan, Pro-gram Coordinator, CRG.


A new term has entered the lexicon ofthe 21st century with the explosion of thefertility industry: eggsploitation. JenniferLahl, a San Francisco-based nurse, usedthe term as the title of her documentaryon the subject. She defines “eggsploitation”as follows: "to plunder, pillage, rob, despoil,fleece, and strip ruthlessly a young womanof her eggs, by means of fraud, coercion ordeception, to be used selfishly for another'sgain, with a total lack of regard for the well-being of the donor."

Since 1978, when the first test tubebaby was produced through in vitro fertil-ization, and just five years later when thefirst embryo was created outside theuterus using a donated egg, the fertilityindustry has mushroomed into a multi-billion dollar global business. Nearly everycollege campus in the United States isblanketed with advertisements for eggdonors from fertility clinics and brokers.A Wild West, anything goes climate pre-vails in the U.S. where there is virtuallyno regulation or oversight of this $6.5 bil-lion annual business. Young women arelured by ads offering them up to $50,000for their eggs; up to $100,000 for Harvardor Yale eggs. The numbers speak for them-selves: in 2007, the Centers for DiseaseControl & Prevention reported 17,405 fer-tility treatment cycles. What is generallyunknown is that approximately 70% ofAssisted Reproductive Technology cyclesfail.

Despite the industry's great PR andeffusive media stories of celebrity par-ents having babies through donated eggsand surrogates, there is an alarmingabsence of published, peer-reviewed med-ical research and data on egg extractionand the risks posed to women who serveas donors. As Drew Moffitt, MD, a fertil-ity and reproductive endocrinologiststated in testimony before Congress, "Inmedicine, there tends to be a desire to pub-lish positive findings and not publishnegative findings."

Who are these egg donors? Youngwomen in their 20's, struggling to financecollege and graduate school educations.As young women interviewed in the filmexplain, the industry uses bait-and-switchtactics whereby they are enticed by the

money offered and then pressured tocontinue with the often brutal proce-dures with appeals to altruism andwithout information provided regardingthe health risks involved. The brokers andclinics exploit the patriarchal culture's psy-chological conditioning of females to be ofservice to others and employ guilt-induc-ing tactics to ensure their compliance. Inessence, the donors are nameless, face-less women, too often used and leftforgotten.

Jennifer Lahl, who wrote, directed andexecutive produced the film, is among agrowing number of advocates for women'shealth and rights arrayed against a mas-sive industry of physicians and researcherswho have every incentive to avoid bothdisclosure of health risks and protectionof donors when the profits involved are sohigh. In addition, industry lobbyists willquickly rally to prevent regulation andoversight of this enormous cash cow.

So what are the risks associated withegg extraction? The powerful drugsdonors must take contain the short-termrisk of ovarian hyperstimulation syndromealong with surgical, anesthetic, emotionaland psychological risks. Additional risksinclude pulmonary infarctions, fluidimbalances, stroke, clotting, perforationof the bowel or bladder, bleeding, produc-tion of adhesions which cause futureinfertility, and death. Long-term risksinclude breast, ovarian and endometrialcancers and future infertility.

Women normally ovulate one or twoeggs a month but egg donors are admin-istered self-injected synthetic hormonesto produce dozens of eggs, so-called super-ovulation. The drug Lupron (leuprolideacetate) is frequently used to stop thedonor's menstrual cycle, inducing amenopausal state, in order to be synchro-nized with the surrogate's so a successfulpregnancy can result. Lupron, however, isnot intended for fertility use and is unap-proved by the U.S. Food & DrugAdministration for that purpose. Onedonor featured in the documentary expe-rienced a stroke after taking Lupron whichparalyzed her left side and caused braindamage.

Other horror stories include the death

of Jessica Wing at the age of 34 who wasdiagnosed with colon cancer after sellingher eggs three times during her twenties.Angela had a history of migraines whosehealth concerns were dismissed by the fer-tility clinic. After consulting with aneurologist, she was told that the hor-mones used could trigger a seizure whencombined with birth control pills andmigraines. When she reported this infor-mation to the clinic, she was told thatbacking out was unacceptable; in Angela'swords: "I was no longer in control." Cindy,a combined MD/PhD student, began hem-orrhaging after surgical extraction and herblood pressure dropped to dangerous lev-els. An artery had been punctured by theneedle and the situation was exacerbatedby the hyperstimulation which weakensblood vessels.

The young woman who had a strokerevealed that her General Practitioner toldher mother that "The industry knew thatthis would happen sooner or later; they'vejust been rolling the dice and it fell on yourdaughter." As with so many corporatepractices, when the profits generated farexceed the harms caused, it is considereda risk worth taking. In other words, greedcombined with impassioned desires forparenthood trump public health concernsof the most vulnerable.

As Suzanne Parisian, MD, formerChief Medical Officer of the FDA states inthe film, without the benefit of medicalresearch or tracking, it is simply impossi-ble to know what all the risks are. "It's onething to say they don't know the risks; it'sanother to know that nobody's going tolook either and so you're (the egg donor)really alone." The situation is summed upsuccinctly by Jennifer Lahl: "Until actionis taken to protect potential egg donors,we will continue to hear more storiesabout the reckless endangerment of vul-nerable young women." The message ofthe documentary is that if you are a youngwoman thinking about donating youreggs, think again.

Kathleen Sloan is Program Coordinatorat CRG.


EggsploitationDreams and profits at the cost of young women’s health

BY KATHLEEN SLOAN

FILM REVIEW

DNA Alarm Systems:"You Steal, You'reMarked"

Are you a storeowner who has beenburglarized? Frustrated that your alarmdidn't help you nab the culprit? If old fash-ioned security cameras just aren't doingthe trick, why not try a new system: onethat sprays synthetic DNA all over thethief.

In fact, this product does exist. Somestores in the Netherlands are already try-ing it out–with mixed results–and ADT ismarketing a similar product in Australia,calling it "DNA Guardian." The mecha-nism sounds simple: a can is mounted overthe door, and when triggered, it sprays afine mist onto whoever passes below it.The mist, which is only visible under UVlight, contains synthetic DNA with spe-cific markers that can connect theculprit–once collared–to the scene of thecrime.

The product's distributors emphasizethat the system's value is actually in pre-vention rather than capturing the thief-infact, the system has led to zero arrests sofar. The preventative value relies largely,they say, on the mystique of DNA, whichcauses potential crooks to take the sign onthe door seriously: "You Steal, You'reMarked."

NCAA ImposesMandatory Sickle CellTesting

As of August 1, the National CollegiateAthletic Association requires all DivisionI student-athletes–about 170,000 people–to be tested for sickle cell anemia.

The intention is to protect athleteswho carry the trait, a response to a lawsuitfiled against the NCAA by the family of a19-year-old who died after overexertion ata football practice, unaware that he hadsickle cell anemia. However, mandatorytesting carries significant privacy and dis-crimination concerns.

"This could have an extraordinarilyheavy impact on black athletes," says TroyDuster, professor of sociology at New YorkUniversity. "You are going to be pickingout these kids and saying, 'You are goingto be scrutinized more closely than any-one else.' That's worrisome."

The Sickle Cell Anemia Association ofAmerica and the U.S. Health and HumanServices Department's Advisory Commit-tee on Heritable Disorders in Newbornsand Children are among those voicingconcerns.

While many athletic directors, doctorsand parents support the program, R. Rod-ney Howell, chair of the HHS committee,is not convinced.

Genetically ModifiedMosquitoes ReleasedInto the Wild

In early November, U.K. biotech com-pany Oxitec announced that geneticallymodified mosquitoes of its design hadbeen released in the Cayman Islands-ayear earlier.

The mosquitoes are designed to reducedengue fever by mating with existing pop-ulations and producing larvae that dieunless exposed to the antibiotic tetracy-cline. Over three million mosquitoes werereleased in the Caymans-unbeknownst toopponents of the project.

Oxitec defends the release, saying theyworked with the Cayman government tocarry out a risk analysis and gather localinput, but say they made "no special efforteither to spread the word internationallyor not to."

Although safety studies have not beenreleased from the Cayman trials, newreleases are planned for Malaysia andOxitec is seeking approval from Panama,Brazil and the United States.


"If you are going to test for sickle celltrait, it should not be done in the lockerroom by a coach."

The NCAA stands by the requirmentand is considering extending the manda-tory testing to Division II athletes.

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U.S. Health and Human Services Sec-retary Kathleen Sebelius recentlydisbanded the Secretary's Advisory Com-mittee on Genetics, Health, and Society, adecision that was made by the Secretaryin close concert with Dr. Francis Collins atthe National Institute's of Health.

SACGHS was initially created eightyears ago by the Department of Health andHuman Services to advise it and other fed-eral agencies on the ethical, legal and socialimplications of emerging genetic tech-nologies. A diverse body of nationalexperts, SACGHS has played an impor-tant role in addressing these growingissues with thoughtful and well reasonedresearch and analysis.

A statement posted on the SACGHSwebsite subsequent to the decision to dis-band it declared: " As part of the renewalprocess for any committee establishedunder the Federal Advisory CommitteeAct, the government must periodicallyassess the continuing need for the com-mittee...In its nearly 10 years of operation,SACGHS has addressed all the major top-ics delineated in its charter."

Really?According to its charter, SACGHS was

charged with: - Assessing how genetic technologies

are being integrated into health careand public health,

- Studying the clinical, public health,ethical, economic, legal, and societalimplications of genetic and genomictechnologies and applications,

- Identifying opportunities and gaps inresearch and data collection analysisefforts,

- Examining the impact of currentpatent policy and licensing practiceson access to genetic technologies,

- Analyzing uses of genetic informa-tion in education, employment,insurance, and law,

- Serving as a public forum for discus-sion of issues raised by genetic andgenomic technologies.How can one argue with a straight face

that such goals have been fully realized?

From its groundbreaking work on theGenetic Information NondiscriminationAct to influential reports on issues rang-ing from genetic testing guidelines todirect-to-consumer genetic testing, it canhardly be claimed that SACGHS was irrel-evant.

Over the years, SACGHS had becomethe central forum for discussing the rapiddevelopments in genetic policy; a forumdesigned to facilitate inter-agency dis-cussions and one that was open to both thepublic and a diverse array of private stake-holders.

So what was the real reason for dis-banding SACGHS? Cost was cited as acontributing factor to the decision, thoughconsidering the fact that SACGHS was abody made up of largely uncompensatedmembers, this hardly seems a legitimatejustification. The annual budget forSACGHS was less than $200,000 accord-ing to its charter, a paltry sum in its ownright; but consider, that's out of a total NIH2010 budget of $31 billion!

Some have suggested that there ismore to it, that by making recommenda-tions at odds with industry and itsgovernment supporters, the SACGHS ini-tiated its own demise. Lately theCommittee has released a couple of con-troversial reports, in particular a reportentitled “Gene Patents and Licensing Prac-tices and Their Impact on Patient Accessto Genetic Tests,” which found that:

Trends in patent law appear to poseserious obstacles to the promise ofthese developments [in geneticresearch and clinical practice]. Patent-ing has moved upstream; instead ofcovering only commercial products,patents can now control foundationalresearch discoveries, claiming the puri-fied form of genes. Fragmentedownership of these patents on genes bymultiple competing entities substan-tially threatens clinical and researchuse.

The report was widely condemned byindustry and its supporters. The Biotech-nology Industry Organization President

Jim Greenwood declared at a press con-ference that the report would go so far asto:

discourage investment in biotech inno-vation, hobble the transfer offederally-funded research, undermineuniversity research programs, andharm patients who are waiting for life-saving therapies and diagnostics yet tobe developed.

An industry supporter, writing inGenomeWeb, wrote “I'm not as sympa-thetic to SACGH's demise…because it hasmade decisions that could threaten clini-cal labs and patient care.”

Perhaps it's just the natural hubris ofscientists that think they know all theanswers without necessarily understand-ing the questions. Either way, in theabsence of SACGHS or something simi-lar, there will no longer be a central andindependent forum to address the ethical,legal and social issues of emerging genetictechnologies. Yet the challenges posed bythe rapid advances in genomic research,many as yet unidentified, will continue topresent themselves. The disparate agen-cies left to address these issues have noclear expertise in doing so and no mech-anism to discuss how these many issuesinterconnect and affect each other (repre-sentatives of at least 19 Federaldepartments or agencies were representedas non-voting members on SACGHS).

The public deserves better from itsgovernment. Genetic research and tech-nology will continue to have profoundimplications for public health, mostentirely positive, but the eager enthusiasmtoward emerging genetic technologiesmust be paired with an open and accessi-ble discussion of ethical concerns.

Jeremy Gruber, JD, is President and Exec-utive Director of CRG.


Is Government Getting Out of the Ethics Business?The Secretary’s Advisory Committee on Genetics, Health, and Society was disbanded - shortlyafter releasing a gene patent report that didn’t sit well with the biotech industry

BY JEREMY GRUBER

Kane1. Diamond v. Diehr, 450 U. S. 175, 185 (1981).2. The Supreme Court has stated: "Phenomena

of nature, though just discovered, mentalprocesses, and abstract intellectual conceptsare not patentable, as they are the basic toolsof scientific and technological work."Gottschalk v. Benson, 409 U.S. 63, 67 (1972).

3. 35 U.S.C. § 101. The statute authorizes thepatenting of "any new and useful process,machine, manufacture, or composition ofmatter." Id.

4. Association for Molecular Pathology v. U.S.Patent & Trademark Office, 702 F. Supp.2d181 (S.D.N.Y. 2010).

5. Id. at 227.6. Id. at 232.7. Id. at 198.8. Eileen M. Kane, Splitting the Gene: DNA

Patents and the Genetic Code, 71 TEN-NESSEE LAW REVIEW 707, 752 (2004).

9. Lily E. Kay, WHO WROTE THE BOOK OFLIFE?: A HISTORY OF THE GENETICCODE (2000).

10. International Human Genome SequencingConsortium, Finishing the EuchromaticSequence of the Human Genome, 431NATURE 931 (2004).

11. Kane, supra note 8, at 753.12. Funk Bros. Seed Co. v. Kalo Inoculant Co.,

333 U.S. 127, 130 (1948).13. Kane, supra note 8, at 753.14. Bilski v. Kappos, 130 S.Ct. 3218 (2010). The

Supreme Court has now rejected the machineor transformation test as the exclusive test forpatent eligibility, which was used by the judgeto decide the method claims in AMP.

15. Lab. Corp. of Am. Holdings v. MetaboliteLabs., Inc., 548 U.S. 124 (2006).

16. Prometheus Labs. v. Mayo CollaborativeServs., 581 F.3d 1336 (Fed. Cir. 2009), vacatedand remanded, 2010 WL 2571881 (U.S. June29, 2010).

17. Classen Immunotherapies v. Biogen IDEC,304 Fed. Appx. 866 (Fed. Cir. 2008), vacatedand remanded, WL 2571877 (U.S. June 29,2010).

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Patent and Trademark Office, 702 F.Supp.2d181 (SDNY 2010).

2. Brief of Amici Curiae Christopher M. Hol-man and Robert Cook-Deegan in Support ofNeither Party, Association for MolecularPathology v. US Patent and Trademark Office,United States Court of Appeals for the Fed-eral Circuit Docket Number 2010-1406,available athttps://docs.google.com/fileview?id=0B9_llJGo9WK0OWVkYjg3NjItYzRjYi00ODIyL-

WIyMjAtYmJkZDQxMGZmYTZi&hl=en&pli=1 (last visited December 2, 2010).

3. Commercial Biotechnology: An InternationalAnalysis (Washington, D. C.: U.S. Congress,Office of Technology Assessment, OTA-BA-218, January 1984); U.S. Congress, Office ofTechnology Assessment, Biotechnology in aGlobal Economy, OTA-BA-494 (Washington,DC: U.S. Government Printing Office, Octo-ber 1991).

4. Emerging Healthcare Issues: Follow-On Bio-logic Drug Competition, Federal TradeCommission Report (June 2009).

5. Revised Draft Report on Gene Patents andLicensing Practices and Their Impact onPatient Access to Genetic Tests (the SACGHSReport), available athttp://oba.od.nih.gov/oba/SACGHS/SACGHS%20Patents%20Report%20Approved%202-5-20010.pdf (last visited December 2, 2010).

6. 35 USC 103.7. 35 USC 112.8. Joshua D. Sarnoff & Christopher M. Holman,

“Recent Developments Affecting the Enforce-ment, Procurement, and Licensing ofResearch Tool Patents,” 23 Berkeley Tech. L.J.1299 (2008).

Noonan1. Walsh et al., 2003, "Science and the Law:

Working Through the Patent Problem," Sci-ence 299: 1020).

2. Straus, 2002, Genetic Inventions, IntellectualProperty Rights and Licensing Practices).

3. Nicol et al., 2003, Patents and MedicalBiotechnology: An Empirical Analysis ofIssues Facing the Australian Industry, Centrefor Law & Genetics, Occasional Paper 6.

4. Nagaoka, 2006, "An Empirical Analysis ofPatenting and Licensing Practice of ResearchTools from Three Perspectives," presented inOECD Conference in Research Use ofPatented Inventions, Madrid).

5. Shapiro, 2001, "Navigating the PatentThicket: Cross Licenses, Patent Pools, andStandard Setting," In: Innovation Policy andthe Economy 1: 119-50.

6. Heller & Eisenberg, 1998, "Can Patents DeterInnovation? The Anticommons in BiomedicalResearch," Science 280: 698-701.

Greenfield1. Yochai Benkler, Free as the Air to Common

Use: First Amendment constraints on Enclo-sure of the Public Domain, 74 N. Y. U L. Rev.354 (1999); Yochai Benkler, "ConstitutionalBounds of Database Protection: The Role ofJudicial Review in the Creation and Definitionof Private Right in Information," 15 BerkeleyTech. L. J. 535 (2000)' Yochai Benkler, "SirenSongs and Amish Children: Autonomy, Infor-

mation and the Law," 76 N. Y. U. L. Rev. 23(22001)

2. U.S. Const. Art. I, §8, cl.83. 35 U. S. C. 4.. John Thomas, SYMPOSIUM 2002: THE

FUTURE OF PATENT LAW: LIBERTY ANDPROPERTY IN THE PATENT LAW, 39Hous. L. Rev. 569 at 570

5. Eugene Thacker, The Global Genome:Biotechnology, Politics and Culture (2005) at20; Dan Burk, “The Problem of Process inBiotechnology,” 43 Hous. L. Rev. 561, 582-587(2006).

6. See. e.g., Dorothy Nelkin & M. Susan Lindee,The DNA Mystique: The Gene as a CulturalIcon 1-18 (1995)

7. Jonathan Kahn, "What's the Use? Law andAuthroity in Patenting Human Genetic Mate-rial" 14 Stan. L & Pol'y Rev. 417 at 417-418

Beeson1. Hamilton, J. 2000. What are the costs? Stan-

ford Magazine.http://www.stanfordalumni.org/news/maga-zine/2000/novdec/articles/eggdonor.html

2. Schneider, Jennifer. 2008. Fatal colon cancerin a young egg donor: A physician mother'scall for follow-up and research on the long-term risks of ovarian stimulation. Fertility andSterility, 90:2016.

3. ECASRM (Ethics Committee of the Ameri-can Society for Reproductive Medicine).2007. Financial Compensation of oocytedonors. Fertility and Sterility. Vo. 88,No. 2,August. pp. 305-309.(quote on p. 6).

4. Andrews, L. 2000. The Clone Age: Adven-tures in the New World of ReproductiveTechnology. New York:Henry Hold and Co. p.35. ; Corea, G. 1988. The Mother Machine:Reproductive Technologies from ArtificialInsemination to Artivicial Wombs. London:The Women's Press, p.318.

5. Guidice L., Santa E. and R. Pool (Eds.) 2007.Assessing the Medical Risks of HumanOocyte Donation for Stem Cell Research:Workshop Report. Institute of Medicine andNational Research Council of National Acad-emies. Washington, DC: National AcademiesPress. Pp. 10-11.

6. Guidice L. p. 197. Guidice, p. 208. Guidice, p. 20.9. Guidice, p. 18.10. Kramer, W., J. Schneider, and N. Schultz.

2009. "US oocyte donors: retrospective studyof medical and psychosocial issues." HumanReproduction. September.

11. Guidice, p. 26.12. Guidice, p. 13.13. Brinton, L. 2007. Long-term effects of ovu-

lation-stimulating drugs on cancer risk.


Endnotes

Reproductive BioMedicine Online. Vol. 15.No.1, pp. 38-44.

14. Brinton, p.15. Cody, P. 2008. DES Voices: From Anger to

Action. Columbus Ohio: DES Action. P. 1716. National Institutes of Health.

http://www.nhlbi.nih.gov/whi/whi_faq.htm17. National Cancer institute. 2007.

http://www.cancer.gov/newscenter/pressre-leases/2007/breastincidencedrop

18. Calderon-Margalit, R. et al. 2008. "CancerRisk After Exposure to Treatments for Ovula-tion Induction." American Journal ofEpidemiology, (Advance Access publishedNovember 26, 2008).

19. Demirol A, Suleyman G, and Gurgan T.2007. Aphasia: an early uncommon complica-tion of ovarian stimulation without ovarianhyptestimulation syndrome. ReproductiveBiomedicine Online. January.

20. Coli, S, et al. "Myocardial infarction compli-cating the initial phase of an ovarianstimulation protocol." International Journal ofCardiology, Vol. 115, Issue 1, Jan. 31, 2007.

21. Edwards, R.G. 2007. "Are minimal stimula-tion IVF and IVM set to replace routine IVF?Reproductive Biomedicine Online. Vol. 14,No. 2., Pp. 267-270.

22. Dennis, C. 2006. Cloning: Mining thesecrets of the egg. Nature. Vol.439, 9. Febru-ary. Pp. 652-655.

23. Norsigian J. 2002. Emerging Biotechnolo-gies: Cloning. Testimony to Senate Health,Education, Labor and Pensions Committee.March 5.http://www.ourbodiesourselves.org/book/companion.asp?id=25&compID=67&page=9

24. Son, Bonghee. 2006. "The Hwang Woo-sukcase and the significance of a damage claimfor victims of egg extraction." Paper pre-sented at the International Forum Envisioningthe Human Rights of Women in the Age ofBiotechnology and Science. Seoul, Korea.

25. Memorandum of Points and Authorities inSupport of Petition for Writ of Mandate andAlternative Writ of Mandate/Order to ShowCause. 2004 (Undated, no case number) PaulBerg, PhD; Robert Klein; and Larry Goldstein,Petitioners vs. Kelvin Shelly, Secretary ofState of California, Respondent, GeoffBrandt, State Printer; Bill Lockyer. AttorneyGeneral of California ; Tom McClintock; H.Rex Green John M. W. Moorlach; Judy Norsi-gian; Francine Coeytaux; Tina Stevens; Does Ithrough X, inclusive, Real Parties In Interest.Also see: Paul Berg, Ph.D; Robert N. Klein;and Larry Goldstein, Petitioners v. KevinShelly, Secretary of State of California,Respondent, Case No. 04CS01015, SuperiorCourt of the State of California, "Declarationof Dr. Stuart A. Newman, PhD., in Oppositionto Petition for Writ of Mandate and Alterna-tive Writ of Mandate/Order to show Cause,"August 4, 2004, p. 2.

26. National Academies of Science. Final Reportof the National Academies' Human Embry-onic Stem Cell Advisory Committee and 2010Amendments To the National Academies'Guidelines for Human Embryonic Stem CellResearch. Section 3.4b.http://www.nap.edu/openbook.php?record_id=12923&page=27#p2001b5399970027001

27. Personal communication. December 1,2010.

28. Dolgin, E. CIRM to Pay foreggs?http://humanebiotech.com/cirmwantseggs.html

29.http://californiastemcellreport.blogspot.com/2010/06/stem-cell-agency-bars-public-from.html

30. CIRM-MRC Human Somatic Cell NuclearTransfer Workshop Report , June 13-14, 2010.www.cirm.ca.gov/files/PDFs/.../Human_SCNT_Workshop_Report.pdf

31. California Department of Public Health

Human Stem Cell Research Advisory Com-mittee Meeting. November 30, 2010.

Eyal1. Guichon, J. "Don't let market forces govern

human procreation," BioNews, 22.November2010.

2. Scott Carrny, Red Market Blog," Interna-tional Baby Market"http://redmarkets.com/2010/08/interna-tional-baby-maker.html

3. The Nuremberg Code (1947) In: MitscherlichA, Mielke F. Doctors of infamy: the story ofthe Nazi medical crimes. New York: Schu-man, 1949: xxiii-xxv.

4. The World Health Organization (WHO) is anorgan of the United Nations and is the leadingauthority on health within the United Nationssystem

5. http://conventions.coe.int/Treaty/Com-mun/QueVoulezVous.asp?NT=164&CL=ENG

6. http://conventions.coe.int/Treaty/Com-mun/QueVoulezVous.asp?NT=186&CL=ENG

7. The Helsinki Declaration was developed bythe World Medical Association. It is not abinding legal instrument, but its principleswere drawn from worldwide regional andnational legislation.

8. Such is the case in the Draft Guiding Princi-ples on Human Organ Transplantation of1991

9. Ingrid Schneider, (2007)10. DIRECTIVE 2004/23/EC OF THE EURO-

PEAN PARLIAMENT AND OF THECOUNCIL of 31 March 2004


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