genewatch vol. 23 no. 4

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

VOLUME 23 NUMBER 4 AUGUST-SEPTEMBER 2010

FEATURESHow Berkeley Came to Abruptly Change Its Genetic Testing Program / Jeremy Gruber

In Their Own Words: Genetic Testing Company 23andMe

Biolab Safety: A View From the Inside / Nancy ConnellISSN 0740-9737

GeneWatch is a unique publication. We cover controversial issues,but we toe a difficult line between strictly objective journalism and sin-gle-minded advocacy. Just to left of this editorial, you'll find the fineprint: “The views expressed herein do not necessarily represent theviews of the staff or the CRG Board of Directors.” Except, of course—as in this issue—when those people are contributing articles of theirown.

The purpose of each issue of GeneWatch is not to simply report what'shappening out there, nor is it to tell you what you ought to believe, evenif some of the pieces on the following pages fall into those descriptions.As I see it, if you read an issue of GeneWatch front to back, you oughtto have learned something; most importantly, you ought to havethought. If you read every page of GeneWatch and your preconceivedopinions have not been challenged, we came up short. If you can readthe entire issue and never find yourself in disagreement with an author,we haven't done our job.

That job might be more difficult if our Board of Directors held mono-lithic views. While CRG has published position papers on everythingfrom gene patents to biocolonialism, opinions within the organiza-tion are nuanced to say the least. This issue—Direct-to-ConsumerGenetic Testing—is a prime example.

You will find several articles by CRG Board members in the follow-ing pages, and you will hardly find a united front. Sheldon Krimsky tar-gets the risks of allowing companies to market genetic tests toconsumers without meaningful regulation; Paul Billings defends DTCtesting as a tool to empower consumers to take a more central role intheir own health care; Robert Green, with Jordan P. Lerner-Ellis and J.David Ellis, balances the potential risks and benefits and concludes thatwe simply don't have all the answers yet. CRG has historically taken aquite critical view of DTC testing, but as evidenced by the highlyinformed views of our own Board members and other contributors inthis issue, such a complex topic cannot be boiled down to a thumbsup or thumbs down. It's easy to just tell someone what they ought tobelieve—which is why you won't find us doing it.

And if you've read this far and are still wondering “What exactly isdirect-to-consumer genetic testing?” … well, I'm afraid you'll just haveto read on. Go into it as a blank slate. Think about where you stand.And let me know if we made it too easy for you.

2 GENEWATCH AUGUST-SEPTEMBER 2010

Editorial Sam AndersonGENEWATCH

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 Treasurer

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

ANDREW IMPARATO, JDPresident and CEO, American Association of

People with Disabilities

RAYNA RAPP, PhDNew York University

PATRICIA WILLIAMS, JDColumbia University

EDITORIAL COMMITTEE

Ruth Hubbard Sheldon Krimsky

EDITOR & DESIGNER

Sam Anderson

AUGUST-SEPTEMBER 2010 VOLUME 23 NUMBER 4

Unless otherwise noted, all material in this publication is protected by copyright bythe Council for Responsible Genetics. All rights reserved. GeneWatch 23,4

0740-973

COVER ART

Sarah Kim

STAFF

Jeremy Gruber, President and Executive DirectorSheila Sinclair, Manager of OperationsSam Anderson, Editor of GeneWatchKathleen Sloan, Program Coordinator

Andrew Thibedeau, Senior FellowMagdalina Gugucheva, Fellow Sarah Kim is a graduate of Massachusetts

College of Art and Design who enjoys working onany and all kinds of illusration. You can see moreof her work at www.skimilkart.com. This isSarah’s fourth GeneWatch cover.

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GeneWatch welcomes all comments, as well as letters to the editorfor inclusion in upcoming issues. Please email [email protected] if you would like to submit a letter (200 words or less,please) or with any other comments or queries.

What do you think?

VOLUME 23 NUMBER 4 GENEWATCH 3

Lessons Learned: How Berkeley Came to Abruptly Change Its

Genetic Testing ProgramJEREMY GRUBER

Direct-to-Consumer Genetic Testing:What’s the Prognosis?

JORDAN P. LERNER-ELLIS, J. DAVID ELLIS,ROBERT C. GREEN

The Broken Clock: Accuracy and Utility of DTC Tests

AN INTERVIEW WITH JAMES EVANS

Consumer Genomics and the Empowered Patient

PAUL BILLINGS

Not What the Doctor OrderedSHELDON KRIMSKY

DTC Genetic Testing: A UK PerspectiveHELEN WALLACE

False ReassuranceADELE SCHNEIDER

In Their Own Words: 23andMeWITH ANNE WOJCICKI AND ASHLEY GOULD

Genetic Counselors: Don’t Get TestedWithout One

AN INTERVIEW WITH ELIZABETH KEARNEY

DTC Genetic Testing: Consumers and Privacy

JEREMY GRUBER

The $1,000 Genome: Caveat EmptorANDREW THIBEDEAU

Biolab Safety: A View From the InsideNANCY CONNELL

Topic Update: Familial DNA Profiling

Commentary: Fishy Business at the FDAERIC HOFFMAN

Endnotes

4

Contents

CRG played a crucial rolein putting the brakes onUC Berkeley’s plan togather DNA from incoming students (p. 4)

6

8

10

11

12

14

16

18

20

22

24

25

26

“These companies want tohave it both ways. Pick oneor the other: it’s either medically important or itisn’t.” (p. 8)

Access to genetic testingcan empower patients -but do the risks outweighthe benefits? (p 10 and 11)

17Direct-to-consumer genetictesting company 23andMe tellstheir side of the story (p 16)

Nancy Connell knows a bit aboutsafety in biolabs - she runs one (p22)

A killer is found through a familialDNA search—but the techniqueremains highly problematic (p. 24)

Last month, the University of California,Berkeley changed course after months ofintransigence and made significant changesto their controversial “Bring your Genes toCal” freshman genetic testing program. Themost prominent modification was the elim-ination of any individually identifiable analy-sis of student DNA. While this change ofcourse appeared abrupt, it was the result ofseveral months of significant and mostlybehind-the-scenes work. The lessonslearned from successfully pressuring theUniversity to revise its program can pro-vide a blueprint for future successes in steer-ing the development of biotechnologytowards the advancement of public health,environmental protection, equal justice, andrespect for individual rights.

In May of this year, the University of Cal-ifornia, Berkeley announced that it would besending incoming freshman a cotton swabwith which to send in a DNA sample to betested for three gene variants that help reg-ulate the ability to metabolize alcohol, lac-tose and folates as part of a program for theclass of 2014 that would focus on geneticsand personalized medicine. The announce-ment, including rough details of the pro-gram, brought swift condemnation from anumber of quarters for the lack of due con-sideration for issues ranging from the pri-vacy protections for the DNA samples andthe data generated from them to issues ofimproper informed consent and conflictsof interest. Noted professors at Berkeley,from Kimberly Tallbear, Troy Duster, CharisThompson and David Winickoff to Nancy-Scheper Hughes, Paul Rabinow and LauraNader, as well as academics outside Berke-ley, such as Hank Greely at Stanford, GeorgeAnnas at Boston University and DebraGeenfield at UCLA all organized, and raisedtheir voices within and without the univer-sity (and continued to speak out during thecourse of the summer). Organizations suchas the Council for Responsible Genetics(CRG) and the Center for Genetics and Soci-ety issued serious point by point critiques of

the program as well as brought public atten-tion to the issue through significant mediacoverage during the first few weeks follow-ing the program's announcement. Manyother members of the public and mediaspoke out as well.

Unfortunately, as is often the case, theinitial outcry was not enough. While theUniversity met with many of their academiccritics, it failed to seriously consider and ulti-mately rejected their concerns. The mediaattention ran its course. Having weatheredthe criticism, indeed seemingly enthralledby it, Berkeley became even more dismissiveand convinced of the virtue of its program.

And that is where the story would likelyhave ended, had many critics of the Berke-ley program not urged the Council forResponsible Genetics to dig deeper. Raisingyour voice and taking a public position on anissue is the easy part of advocacy work. Sel-dom do organizations like ours have theresources to roll up their sleeves and con-duct the incredibly time consuming andunglamorous work that is generally requiredto truly move an issue forward. Fortunatelyfor us, we had an incredibly bright and ener-getic intern assisting us for the summer andthere was no greater motivating factor thanBerkeley's arrogance!

With our charge of halting this highlyproblematic experiment, CRG began amulti-prong advocacy plan. We began build-ing a loose coalition of organizations to workon the Berkeley program. We had learnedour initial lesson, that a group of organiza-tions and individuals focused exclusively onbiotechnology issues was insufficient toaffecting change on its own. This time werecruited a much larger and varied groupof organizations, ranging from civil rightsand privacy groups such as the AmericanCivil Liberties Union (ACLU), ElectronicFrontier Foundation (EFF), Privacy RightsClearinghouse and World Privacy Forum toconsumer protection groups such as Con-sumer Watchdog as well as more focusedorganizations such as the Alliance for

Humane Biotechnology.We filed a number of public records

requests with Berkeley under California'sSunshine Act, similar to the federal Freedomof Information Act, in an attempt to learnmore details about the program, includinginformation regarding the program's undis-closed funding source. Berkeley oftendelayed, and in some cases failed to complywith our requests, necessitating us to file aformal complaint with the Fair Political Prac-tices Commission (which had enforcementauthority over some of our requests) thatresulted in a rare rebuke to the University.We also sent out a staggered series of pressreleases to the media with new informationas we discovered it, keeping the issue on theirradar.

We conducted a significant amount oflegal research in our attempt to stop the pro-gram from moving forward, evaluating everyfacet of Berkeley's plan to look for opportu-nities for a legal or regulatory challenge. Thisresearch resulted in an extensive memoran-dum outlining Berkeley's potential regula-tory and legal breaches and the opportunities


Lessons Learned: How Berkeley Came toAbruptly Change Its Genetic TestingProgram

BY JEREMY GRUBER

for legal action, ranking them in terms oflikelihood of success. The strongest oppor-tunity for challenge that we identified was inthe California Business and ProfessionsCode which regulates clinical laboratorylicensure. Genetic tests, the results of whichare reported back to the individual, are con-sidered clinical laboratory tests by the Cali-fornia Department of Public Health (DPH)pursuant to the Code. Therefore, any labconducting such tests must first obtain alicense from the DPH. Through our publicrecords requests, we determined that Berke-ley had plans to conduct genetic testing ofincoming students at the Genetic Epidemi-ology and Genomics Lab at the School ofPublic Health. We discovered that neitherthe lab (nor its Director or technicians), hadany clinical laboratory licenses from theDPH. We further determined that in fact theonly lab certified for this work was the cam-pus health clinic which was insufficientlyequipped to perform this type of testing. Wefurther determined that no licensed medicalprofessionals were involved in the program,as is also required by the Code.

In the course of researching our memo-randum, we had obtained copies of letterssent by the DPH to several in state direct-to-consumer genetic testing companies a cou-ple of years earlier that warned them of therequirement of proper clinical lab licensure.As the letters were signed, it was relativelyeasy to identify the appropriate individual tocontact at the Department of Public Healthwith our findings. While the DPH con-firmed that our analysis was a correct inter-pretation of the regulatory requirements, theDepartment seemed wary of making publiccomments before having an opportunity tofully investigate. Given that the Universitywould only violate California law upon theactual testing—not yet performed at thattime—it was too early for us to argue Berke-ley was operating illegally.

Then we caught a lucky break. Assem-blyman Chris Norby, a moderate Republican

in the California legislature, introduced a bill(AB 70) that, if enacted, would essentiallyshield the state from any lawsuits as a resultof Berkeley's (or any other public universi-tys') genetic testing program. The costs ofany lawsuit would be borne by the individ-ual university's general funds. While highlyunlikely to pass, the bill proved an invaluabletool to renew media and public attentionon Berkeley's program. We formed a closerelationship with the sponsor's incrediblydedicated staff and began working closelywith them on both substance and strategy.

With this new platform, we drafted mul-tiple organizational sign-on letters with thehelp of our coalition partners both in sup-port of AB 70 as well as urging the legisla-ture to force a more general accounting ofthe Berkeley program. With these letters inhand, the ACLU became an essential ally inusing its deep connections in the legislatureto open doors for multiple meetings betweenthemselves, CRG and EFF with staff in boththe Senate and Assembly. Both the ACLUand EFF also assisted in broadening ouranalysis. The meetings created the neces-sary pressure to hold a hearing on the Berke-ley program. The Alliance for HumaneBiotechnology used its connection with thechairman of the committee holding the hear-ing to weigh in as well. CRG worked closelywith staff to identify those individuals whocould provide testimony beyond that nar-rowly offered by the representatives fromBerkeley including Professors Greely andScheper-Hughes. Lee Tien from EFF andmyself representing CRG also testified at thehearing. Perhaps most importantly, the Cal-ifornia Department of Public Health wascalled to testify. The added pressure on theagency was the final piece we needed.

Just prior to the hearing, the Governor'soffice contacted the DPH and ordered themto issue a statement at the hearing, ratherthan testify. Nevertheless, their statementreflected our initial analysis and the hear-ing elicited a promise from Berkeley, still

unconvinced that the DPH was serious, toabide by the agency's interpretation. A meet-ing between DPH and Berkeley later that dayconvinced them that the agency was indeedserious. Berkeley hastily called a press con-ference the next day to announce significantchanges in the “Bring Your Genes to Cal”program, bringing a media firestorm evenlarger than the one initially covering theannouncement of the program. While someelements of the program have proceeded, it'ssafe to say that most institutions consider-ing a genetic testing program in the futurewill remember Berkeley and invest far moreeffort into crafting an ethical and legallycompliant protocol.

We learned many things from this smallsuccess. We learned that a successful advo-cacy effort requires many hands and diversetalents and that to actually be effective onour issues we need to continue to build rela-tionships and alliances with organizationsthat do not exclusively work on biotechnol-ogy issues, ranging from the civil rights andprivacy communities to the organized labor,disability, patient, consumer protection andenvironmental communities, to academiaand beyond. We need to build strong rela-tionships with legislators and other policymakers as well as the media. We learned thatlegislation, even when unsuccessful, can pro-vide a valuable tool to bring attention to andimpact our issues. And most importantly welearned that there is no substitute for rollingup your sleeves and doing the type of hardwork that often goes unnoticed and is usu-ally unsuccessful. With hard work (and a lotof luck!) we can successfully steer biotech-nology development toward advancing thepublic interest.

Jeremy Gruber, JD, is the President of theCouncil for Responsible Genetics.


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.

companies have taken care to be accurate ontheir websites as to the modest effects ofgenetic risk information, and the importanceof other risks.

By 2009, the DTC controversy revolvedaround conflicting visions of the future ofpersonalized health care. To its supporters,DTC genetic testing offered private, scien-tifically supported and personalized infor-mation about the state of one's health-awayfrom the intrusive gaze of insurance compa-nies, freed from the paternalistic intermedi-ation of harried and often uninformedclinicians seeking to preserve their economicadvantage in an already dysfunctional healthcare system.

To its detractors, DTC genetic testingwas exploiting widespread misunderstand-ing of genetic determinism to market com-mon DNA risk variants that were poorlyunderstood by the scientific community, andprovided little useful information to con-sumers. DTC genetic testing was simply thelatest in an unending series of health-relatedpseudo-interventions, ranging from colonicsto nutraceuticals, for the privileged whocould afford the extra cost. And the majorchallenge was to keep conventional med-ical practitioners from taking it seriously, lestthe cost of medical testing be driven up inresponse to dubious genetic “risks.”

Fast forward to 2010 and the controver-sies have evolved, but by no means disap-peared. For one thing, DTC companies haveexpanded their offerings to include the iden-

tification of variants associated with rarer,more highly penetrant diseases, as well ascarrier states. Examples include BRCA1, cys-tic fibrosis, PKU and Tay-Sachs. These dis-orders are more “fully penetrant” because ifan individual carries mutations, he or shewill either have the disease or be at high riskto develop the disease. Thus, the nature ofthe information being offered in the DTCgenetic testing space is changing. Suchchanges have the potential to make the testresults medically relevant for a small num-ber of people. But this may also increase thepotential for public misunderstanding, sincecompanies will now be offering clinicallymeaningful rare DNA variant informationalongside clinically less relevant, commonDNA variant information.

Another disruptive development thisyear concerns the Food and Drug Adminis-tration's (FDA) regulatory actions. In May,2010, DTC genetic testing almost went retailwhen the Walgreens drugstore chainannounced it would stock $30 DNA collec-tion kits for the DTC company, PathwayGenomics. The attempt to go to market wasblocked at the last moment, and the con-troversy triggered new scrutiny and new rev-elations.

This summer the FDA decided to inves-tigate the use of what it calls laboratorydeveloped tests (LDTs), which had previ-ously been unregulated.1 The agency's mainconcern was focused upon genetic testsintended for use without medical supervi-


Direct-to-Consumer Genetic Testing:What’s the Prognosis?

BY JORDAN P.LERNER-ELLIS

J.DAVID ELLIS

ROBERT C.GREEN

Genetics has been making news lately, inlarge part because of the growing pains of anew and controversial industry: direct-to-consumer (DTC) genetic testing. DTCgenetic testing raises questions involving pri-vacy, how medical tests should be orderedand understood, who should regulate accessto genomic information, and how individualconsumers will understand and act uponsuch information.

DTC genetic testing has been around ona small scale for some years, but began in anew form in November, 2007 when threecompanies (23andMe, Navigenics andDeCodeMe) launched their genome-widescan services within days of each other. Sud-denly, individuals could send in a sample oftheir DNA and receive ancestry informationor a wide variety of medical risk informationbased on the latest discoveries in genetics.In October 2008, TIME magazine recog-nized the 23andMe personal genome serv-ice as “Invention of the Year.” Celebritiesturned over samples of their DNA at trendyand well publicized “spit parties.”

Non-medical services, like ancestry test-ing, provoked few criticisms. The same wasnot true of medical risk reporting, which wasimmediately criticized on two counts. Firstly,the companies were reporting in most caseson DNA variants of common diseases, dis-covered through statistical comparisons ingenome-wide association studies. Whilethese associations were well-established forlarge populations, they typically accountedfor only a tiny fraction of total disease risk.Genetic testing of this kind was hard to jus-tify for an individual, since it provided noclearly useful information to either thepatient or the health care provider.

Secondly, it seemed possible that otherrisks, like family history and lifestyle-cur-rently much better predictors of commondisease-might be de-emphasized to thedetriment of the DTC genetic testing con-sumers. Thus, a customer who was obeseand had a strong family history of type 2 dia-betes might well receive a low genetic riskscore for the disease. To be fair, the leading

sion. FDA scrutiny has grown for several rea-sons, among them greater complexity ofgenetic testing, the role of labs located farfrom the primary care setting, the involve-ment of profit-making firms and the focuson poorly understood genetic risks for com-mon diseases. The FDA notes that patientrisks include “missed diagnosis, wrong diag-nosis, and failure to receive appropriatetreatment.”

The agency later announced it was hold-ing public meetings to gather stakeholderviews on LDTs. As shown through thediverse testimony presented at its July pub-lic meetings2, clinicians, researchers, advo-cates and business executives are far fromunited on the issue of whether or how to reg-ulate genetic tests. During the July hearings,the General Accounting Office (GAO) madea surprise announcement that it had surrep-titiously taped telephone conversationsbetween investigators and representatives ofthe DTC testing companies. The GAOplayed the tapes on the record, and exposeda number of inaccurate statements made bycompany representatives.

It is worth noting that the proposed over-sight of marketplace behavior will not nec-essarily ensure that the services in questionwill improve in accuracy or prognostic value.These goals are not often achieved throughregulation, and physicians are not necessar-ily the best gatekeepers to determine the prosand cons of ordering genetic tests. Moreover,although commercialization has broughtthese regulatory concerns to the forefront,the development of innovations in geneticsis clearly benefiting from the energy andimagination of the biotechnology and DTCtesting industries. It may be that the inter-

play of commercialization and scientificinnovation that is represented in the DTCgenetic testing industry will prove to havelong term value to society. The FDA is thuskeeping a close eye on how innovation willbe affected by its actions.

The Human Genome Project, completedin 2003, is rightly regarded as one of the greatscientific achievements of our generation,well worth its $2.8 billion cost. But what sci-entists have achieved in the intervening years

is every bit as significant: new technologiesthat have reduced the cost of DNA sequenc-ing to one one-hundred-thousandth of whatit was originally. It is considered inevitablethat within the next 5 years, whole genomesequencing will be available to any individ-ual for under $1,000! As it turns out, the bigchallenge for the future will not be thesequencing technologies, but the cost anddifficulty of interpreting the huge amountsof data they generate.

Therein lies the dilemma for scientistsand regulators. On one hand, the DTC test-ing companies may continue to be innova-tors in the interpretation of personal geneticdata. On the other hand, the companies con-cerned will have to make a concerted effortto develop and refine precautionary meas-ures covering a wide range of medical andethical issues. Many unsettling results canturn up as part of an otherwise routinescreening. A child might, for example, befound to have a variant associated with onedisorder, say autism spectrum disorder-andthe very same variant might later be deter-mined to cause a separate neurodegenera-tive disorder. How will this development bereported and explained to the consumer?What procedures if any should be in placefor tracking individual customers long afterthey've ceased doing business with the test-ing company? Examples abound of the chal-lenges created by incidental and unexpectedfindings, and there may be no ready answers.While informed consent is the universal goal,making it work universally is not a simplematter.

Some experts suggest the crucial prob-lem with DTC testing is lack of supervisionby qualified medical personnel. Medical

supervision may often be desir-able, even essential. But there isanother perspective here. Eventhe experts, including medicalgeneticists, continue to strugglewith incomplete and incompati-ble genetic databases, poor riskmodels and disagreements overinterpretation. Moreover, many

primary care physicians are not well versedin genetics and may not know what kindsof tests their patients need. In other words,it is unrealistic to expect that medical super-vision in and of itself will turn DTC tests—or any genetic tests—into accurate andreliable tools.

In summary, difficult questions facemedical professionals and members of thepublic in their attempts to evaluate genetictests. What does a set of genetic results actu-

ally reveal? How will they help promotemedical care? And what difference will test-ing make to the individual's quality of life?These are not theoretical questions. Rightnow many in the testing business are rais-ing the public's expectations by making sug-gestive statements like this one from acompany Web site3: “Let your DNA help youplan for the important things in life.”

Given its mandate, the FDA will have todevote its attention to high-profile issues,especially patient safety, while encouraginginnovation as best it can. Even then, the reg-ulator can only do so much to manage pub-lic expectations, and rising consumerdemand for inexpensive tests is certain to bea strong market mover as this debate unfolds.Over-regulation of a service that consumerswant could simply drive such services off-shore where they could operate over theinternet with impunity. In any case, noamount of market regulation can take theplace of well designed and well-fundedresearch that will help geneticists and otherscientists understand the complexities of thehuman genome in the service of better med-ical care.

Do customers of DTC genetic testingservices really understand what they are pur-chasing? Do they understand the results? Dothey consult their physicians about the infor-mation? Are unnecessary medical testsordered or are valuable health lessonslearned from the overall experience? At thepresent time, we simply do not have all theanswers. The National Human GenomeResearch Institute (NHGRI) has recentlyfunded a proposal to implement the first“before and after” survey of DTC genetictesting in order to better understand thesequestions.

Jordan P. Lerner-Ellis, PhD, is a ClinicalMolecular Genetics Fellow at Harvard Med-ical School & Brigham and Women's Hospi-tal, and leads a genetic test development groupat Partners Center for Personalized GeneticMedicine and Harvard's Laboratory for Mol-ecular Medicine. J. David Ellis, PhD, a consultant in public pol-icy and regulatory affairs, teaches Communi-cation Studies at York University in Toronto. Robert C. Green, MD, MPH professor of Neu-rology, Genetics and Epidemiology at BostonUniversity Schools of Medicine and PublicHealth, and Fellow in Genetics, Harvard Med-ical School, will be co-directing the NHGRIstudy beginning in October 2010, in conjunc-tion with Dr. Scott Roberts of the University ofMichigan. He is a member of the CRG Boardof Directors.


Even the experts, including medicalgeneticists, continue to struggle withincomplete and incompatible geneticdatabases, poor risk models and disagreements over interpretation.

James Evans, MD, PhD, directs the ClinicalCancer Genetics Services at the University ofNorth Carolina. He delivered testimony atthe July congressional hearings focusing ona Government Accountability Office (GAO)investigation which criticized DTC genetictests as “misleading and of little or no prac-tical use to consumers.”

How did you get involved in the GAOreport hearings?

They called me a year or two ago. Theytold me that they were concerned aboutsome of these direct-to-consumer testingcompanies' offerings, and I have some con-cerns as well. I don't think that the sky isfalling because of the existence of thesethings, but I have some concerns. My biggestconcerns have to do with the false claims thatare made by these companies and the factthat we don't really know how to interpretthis kind of information.

So the GAO was looking to design a wayto investigate some of these concerns, andI think that the strategy they ultimately tookwas a good way of investigating and illustrat-ing that we are not ready to interpret thisinformation with any degree of reliability.Then there is a second question: Even if wewere able to interpret these results reliably,

would it tell us anything of any real signifi-cance?

They investigated that first question andeloquently and elegantly demonstrated thatwe are not ready to interpret much of thisdata. There's just no way of reconcilingclaims that it's usable information with thefact that reputable companies conduct analy-ses on the same DNA and come up with rad-ically different interpretations. There's noway to reconcile that information withclaims that it's ready for prime time.

What the GAO did not investigate—andreally could not investigate, I think—was theother issue. The question that remains is:Even if there was consistency, and we learnedto interpret it, would it provide any utility topatients? And the answer to that, I think, islargely a resounding no.

Industry critics have claimed that theGAO's methods were not scientific. Doyou share any of those concerns?

It's an interesting criticism, because theyactually did an elegant experiment; it wasentirely scientific. They had, really, the ulti-mate control. They took the same sampleto different companies and simply presentedthe results: for the same exact sample, onecompany says the individual has an increased

risk of prostate cancer, one says he has anaverage risk, and one says he has a low risk.One of them is right, but it's a little like thebroken clock which is right twice a day.

We have no idea, as that experimentreadily demonstrated, how to interpret someof this genetic information. So the idea thatthe report was not scientific is, I think, arather silly accusation. They did an experi-ment, and the results speak for themselves.

In your testimony you took issue with themarketing claims made by DTC testingcompanies. Are there any specific claimsthat you see commonly made which youfind especially egregious?

Yes. The three big players in this field, thetop strata of these companies, are doing afine job of telling you reliably whichnucleotide you have at a given position, butall of these companies make implicit andexplicit claims that the information willimprove your health. All you have to do islook at their home page on their websites,look at their advertising, and they all makesome claim along the lines of “Understand-ing your genes will be a roadmap to betterhealth” or “Take control of your future withgenetic analysis.” They are all making explicitor implicit claims that knowing your genetic


The Broken Clock: Accuracy and Utility of DTC TestsAn interview with Professor James Evans

information will improve your health; and,frankly, there is no evidence that this is thecase.

They spout platitudes that, for example,people will be motivated to lose weight orlive a healthier lifestyle. Firstly, there is little

evidence that this is the case; secondly, evenif this is the case, if somehow genetic infor-mation has some magical properties thatmake it particularly motivating, then we havea bigger problem: it is arithmetically guar-anteed that for everyone who has increasedrisk of a condition, there are an equal num-ber with decreased risk. If this informationis actually so motivating, we run the signif-icant risk of altering people's behavior for theworse. And frankly, the magnitudes of therisk shift that they are giving people are prac-tically meaningless. Finding out that you areat a twofold or a fifty percent risk of heartdisease over the general population is essen-tially meaningless since these are commondiseases that we remain at significantabsolute risk for whether or not we are atsome relatively decreased genetic risk.

So you are concerned not only about thepossibility of false reassurance, but evenreassurance that isn't necessarily false.

Exactly, it may not even be false! In otherwords, I might tell you that you're at a 50%risk of heart disease over the general popu-lation, but that relative risk is rather mean-ingless. You are still at a high risk for heartdisease simply because it is a very commonmalady. Millions of people out there who areat relatively “low risk” for heart disease endup dying of it!

Because of environmental factors?Yes, and because it's simply a common

disease. But what you're getting at is exactlyright: genetics is only one small part of ourrisk for most of these diseases. Therefore,even if we understood completely the geneticrisk for diabetes and heart disease and can-cer, we still would be left with a huge amountof uncertainty because the causation of thesemaladies is multifactorial.

My other gripe is that in the results theysend to the consumer, some of these compa-nies mix pure entertainment—like “Do you

have thick earwax?”—with a tiny subset ofinformation that is very medically meaning-ful. A small percentage of the informationthey give, like BRCA1 and 2 (relating to riskof breast cancer), and LRK 2 status (relat-ing to risk of Parkinson's disease), are very

predictive, and in the right circum-stances have important medical impli-cations. And yet they're being dumpedinto this big pot with all kinds of teststhat are purely of entertainment valueand some tests that are misrepresentedas being medically useful when they arenot.

I don't have a problem with the pub-lic gaining access to information about theirown genes. I'm not so paternalistic as to sayyou can't have the information in yourgenome. What I do feel strongly about is thatpeople shouldn't be lied to about the signif-icance of that information, and that peopleshould be able to be assured that the claimsthat are made are accurate and that their pri-vacy will be protected.

Do you think that the whole concept of theway these tests are marketed clings tothe old concept that your genome cantell you everything about yourself?

I think what's happened is that there'san understandable impatience to applyall of this wonderful, cool genetic tech-nology to medical care. There's a seduc-tive appeal to thinking that because weunderstand some things about the genome,we now understand a lot about its role inhealth and disease. The difficult and thesober reality, however, is that we don't havea very good grasp of precisely how to relateyour genetic information to your health.That's going to be the work of many years.What we need to do before we just startwilly-nilly selling this idea to people is to findevidence of what's real and what's not, whatworks and what doesn't. All I ask is that wehave data that back up the things that weintroduce into the realm of patient care.

And these companies want to have itboth ways. They implicitly and explicitlymake claims about the health value of thisinformation, and yet on every page of theirresults, they say “this isn't medical advice.”Pick one or the other: it's either medicallyimportant or it isn't. And I would say it is not,demonstrably, as the GAO report reallypointed out.

Since there are plenty of traits testedwhere there is not a lot of utility, do youthink there are traits which are useful forconsumers to know about?

You bet. And I think that there may wellbe reasons that a patient might want to pur-sue various tests in what we consider a non-traditional environment. For example, DNADirect for many years has offered BRCA test-ing. I've never had any problem with whatthey do. They don't misrepresent what theyoffer, and importantly, they have geneticcounselors available to talk to customersabout the meaning of their results. I haven'tlooked at their website in a while, but formany years they offered tests that arguablywere medically valid tests, with real med-ically important results—and they didn't con-flate entertainment with medical information.

I think there are ways of doing this thatare reasonable and responsible, but I don'tthink companies like 23andMe are doing so.

Going back to different companies' radi-cally different interpretations of the sameDNA sample in the GAO report: do youknow of a reason that the interpretationswould be so different?

I think there are several reasons. Now,the reason that the companies will give you

is only part of the truth. They will tell youthe problem is that one company did ninevariants and another company did fourteenvariants. The reason that explanation isn'tthe whole story, and the reason that settlingon everyone testing the same twelve variantsisn't a valid response, is the following: Westill don't understand how to aggregate theseindependent risk factors into a net risk score.Genes interact with each other in ways thatwe are only dimly beginning to glimpse, andgenes interact with the environment. It isentirely possible that you might have variantA, B and C and have an increased risk for acondition, but a person who has variant A,B, C and D is actually at decreased riskbecause of the interaction of variant D withvariant B.

Secondly, genes interact with the envi-ronment. It could well be that an individualwho has variant A, B and C, who should beat increased risk, is actually at average riskin the right environment—because thosegenes and our physiology interact with ourenvironment.

So the reason that they come up with dif-


I don’t have a problem with thepublic gaining access to information about their owngenes. ...

... What I do feel strongly about is that people shouldn’t be lied

to about the significance of that information.

Continued on page 14

My medical school classmates, Harvardphysicians Jerome Groopman and PamelaHartzband (who are married to each other),have railed recently against too much “cook-book” medicine.1 They have cogently arguedthat care of patients is an art; it may not beadequately represented in computer algo-rithms, treatment guidelines or glib qualityassessment reports. They have supportedthe import that the professionalism, expe-rience and expertise of physicians can bringto interactions with patients. This art in thepractice of medicine yields many—and,Groopman and Hartzband would argue,necessary—variations.

But sadly this necessary art can accountfor a multitude of sins. From frank medicalpaternalism, like withholding key facts fromdying patients, to unacceptable variance ininterpretations of pathology or radiologydata, to even the provision of unnecessaryor harmful treatments, variability or artful-ness in medical practice can be wasteful anddeadly. How do we improve care and get themost out of the trust sick people place intheir doctors?

One way, it seems to me, is to makepatients and healthy citizens more knowingand independent actors in the health caresystem. Professional norms demanding real-time honesty with patients, medical mal-practice suits, and the internet have allimproved the power of patients in the doc-tor/patient relationship—and, I would posit,the quality of medical care provided. Mea-suring this change using outcomes likechange in clinical outcome status could bevery difficult at present, even if I am right!

If one's health and the management ofillnesses are in fact one of the more basic per-sonal responsibilities, then allowing peopleto pursue issues of prevention or diseasetreatment in whatever way they see fit could

be reasonable. In such a model, govern-ment's role is to ensure honesty in the rep-resentation and claims of safety oreffectiveness, while physicians act assolicited providers of expert opinion. Theempowered and knowledge-armed citizen isa key agent for the improvement of allaspects of health care and illness prevention.

That is why I founded in 1999 one of thefirst direct-to-consumer (DTC) geneticinformation companies (GeneSage Inc) andwhy I generally support efforts to expand thisknowledge and service channel now. I fun-damentally believe that we all have the rightto know and test things about our bodies,unhindered by physicians gate-keeping thoseactivities. Naturally if someone else is pay-ing for those services (a government,employer or private insurer, for instance),they may have some input into or influenceon what they pay for; but the underlying“right to health” (as Franklin D, Rooseveltput it) lies with each of our fellow citizensand should allow for a wide range of afford-able activities.

Because there is so little known aboutexactly how most of the human genomeimpacts traits and participates in disease,many of the early entrants into DTCgenomics have made overly optimistic, exag-gerated or false claims. This is, of course, trueas well for all the physicians who have prof-fered misinformed advice for decades in thefield. Some of the practices that are offered(DTC or otherwise) or that were noted in therecent Government Accounting Officeinvestigation are bogus and should be cur-tailed. For instance, except in certain rare cir-cumstances (for example, people with PKUshould avoid phenylalanine), there is nogenomic test for the right diet or exerciseprogram that will yield better personalhealth. We may never see the day when

attaching our DNA profiles to the grocerylist as we head to the supermarket is a goodidea!

But if someone wants to obtain a test thatMAY identify a risk for disease or a suscep-tibility to a drug reaction, they should be ableto do so without a physician's intercession.Those ordering such a test in person or froma website ought to have access to reliable andaccurate data about what information thetest may convey. They need to have a reason-able expectation of the quality of the lab thatwill conduct the test with access to easilyunderstood lab performance data. Govern-ments, professional societies, and good mar-ket practices should ensure those conditionsare present. In fact, several states now allowconsumers to order medical tests without adoctor's prescription.

23andMe and Navigenics are both com-panies I know and have advised. The teststhey offer are pretty much “state of the art”in terms of assessing the genes of the humangenome. Soon these companies or others willoffer affordable sequencing assays of all theDNA in the human genome. It will be pos-sible for many people to know exactly whatnucleic acid sequences reside in the nucleiof most of their cells. Of course, the mean-ing of the huge preponderance of this datafor an individual's health or disease develop-ment will take much longer to establish, andwill ultimately be individualized, primarilyby each of us. But as that knowledge


Consumer Genomics and the EmpoweredPatientGenetic testing can help consumers become more knowledgeable and independent actors in their own health care

BY PAUL BILLINGS

The marketing of genetic tests to con-sumers is following a path similar to direct-to-consumer marketing of prescriptiondrugs. And while there are good reasons forthe Food and Drug Administration torescind the rule on prescription drug adver-tising, there are greater risks to consumersin DTC marketing of genetic tests.

Here are some reasons. First, drug com-panies cannot advertise drugs that have notbeen approved by the FDA. Recently, it wasreported that Allergan, the maker of Botox,agreed to pay $600 million to settle chargesthat it illegally advertised the drug for unap-proved uses. Genetic tests, however, do nothave to be federally approved or validated.The tests may or may not do what the com-panies claim they can do. Consumers haveno recourse.

Second, most physicians are not familiarwith the validation criteria, sensitivity, orreliability of genetic tests. They depend uponthe interpretation by the company. If peopletake prescription drugs—whether or notthey are marketed DTC—which turn outeither ineffective or produce an adverseeffect, they can discuss it with their doctor.There are often substitutes that can be used,and adverse effects can be reported to theFDA and to the company.

Genetic tests, on the other hand, areoften patented. There are rarely second opin-ions or the possibility of retests by anothercompany. The test for the breast cancermutations BRCA1 and BRCA2 was for yearscontrolled by one company, Myriad Genet-ics. The successful initial lawsuit by theAmerican Civil Liberties Union challengedthe patent on BRCA, and the appeal willdetermine whether other companies can usethe DNA sequences of BRCA mutations fortheir own tests.

Third, it is easy for DTC advertisers of

genetic tests to overstate the significance ofthe test result, particularly those tests forwhich reliability has not been certified andstandardization has not been set by a profes-sional genetics association. Consumers ofDTC genetic tests are on their own in whatthey purchase (caveat emptor) and what theyread about the product claims (caveat lec-tor).

Fourth, in many cases DTC genetic testscreate “needs” based on fears and falsehopes. While a mutation may have somemeaning in the context of a person's lifestyle,past history, or family health, the range ofreliable interpretation and uncertainty asso-ciated with the consequences of having thosemutations can be quite large. These tests cir-cumvent genetic counselors who can advisepeople about whether they need such a test.Without the help of a trained genetic coun-selor, DTC genetic tests may induce severepsychological stress.

Finally, consumers cannot be certainabout what happens to the information col-lected by genetic testing companies orwhether that information can come back tohaunt them. For example, if consumers whoengage in DTC genetic testing are everinvolved in litigation—say in a disabilityclaim—they can be cross-examined aboutthe test, however poor its reliability or thelikelihood of it yielding a false positive result.

Sheldon Krimsky is Chair of the Board ofDirectors and a founder of the Council forResponsible Genetics. He is a Professor ofUrban and Environmental Policy and Plan-ning at Tufts University.


Not What the Doctor OrderedDirect-to-consumer marketing of genetic tests poses too

many risks to go underregulated

BY SHELDON KRIMSKY

becomes available—unevenly, influenced inmany ways, and with continued debate—some people will want that information, andso-called expert debate should inform butnot stop them.

In general, the prominent commercialentities in the DTC genomics marketplaceprovide understandable information, arededicated to support and participate inimportant research to make the field better,and engage in good clinical practices. Oth-ers do not and should be identified andshunned by consumers as well as scrutinizedby legally designated regulators from HHSand FTC (but not Congressional witch-hunts). In my view, more knowledge andmore highly empowered, well-informedindependently acting consumers are neededto push improvements in genomic medicineand in all aspects of health care. DTCgenomics is part of that. How medical careis ultimately personalized should be a topicthat individuals acting as citizens, con-sumers, patients and in other roles activelycontrol.

Paul Billings is a long-serving member of theCRG Board of Directors, a member of theHHS Secretary's Advisory Committee ofGenetics, Health and Society, and in Octoberwill become the Chief Medical Officer of LIFETechnologies, a provider of tools and reagentsfor research and healthcare.

The recent investigation of direct-to-consumer genetic testing companies by theUS Government Accountability Office hashighlighted a debate about gene test regu-lation that has been ongoing on both sidesof the Atlantic for well over a decade. Whilethe issues raised in the debate have been sim-ilar in all countries—focusing on the qual-ity of tests and their interpretation and issuesof privacy and discrimination—there are alsosignificant differences.

Historical context and the current market

Concerns about DTC genetic testing arenot new, although they have drawn the atten-tion of a much wider audience since thehighly-publicized launch of 23andMe andDeCode's online gene test services in 2007.As Stuart Hogarth describes in a recent arti-cle, the US Task Force on Genetic Testingfirst warned in 1997 that the rapid pace ofcommercialization of new genetic testswould one day outstrip any capacity for over-sight.1

In the UK, a commercially unsuccessfulDTC service for cystic fibrosis carrier test-ing was launched in 1995, leading to thelaunch of a UK Code of Practice in 1997. Thiswas followed in 2002 by the first attempt tomarket a panel of genetic tests associatedwith dietary advice in British high streetstores. Sciona, the UK company responsiblefor the tests, moved to Boulder, Coloradoin 2003, citing adverse publicity about itsproducts. Sciona later became the main sub-ject of the first GAO gene test investigation,published in 2006, and ceased to trade in2009. In the meantime, a succession of othersmall companies entered the market. In theUK, this included both US and UK compa-nies, marketing via the internet, private med-ical practices and alternative healthcareproviders, all making unsubstantiated ormisleading claims.

Beginning in 2003, the UK advisorybody, the Human Genetics Commission(HGC), issued two reports raising concernsand proposing voluntary guidelines andadditional oversight for DTC genetic tests,but in practice it abandoned the 1997 Codeof Practice established by its predecessor

committee, arguing that it had only an advi-sory role, not a regulatory one. The Medi-cines and Healthcare Regulatory Agency(MHRA), which could have regulated thetests, instead became a member of the Min-isterial Medical Technologies StrategyGroup, a body co-chaired by governmentand industry with the aim of promoting ashift to 'early health' in the UK NationalHealth Service (NHS) (including geneticscreening and pre-symptomatic treatment)and resisting regulation on the grounds thatit would stifle innovation.2 The net result isthat no action has been taken to prevent mis-leading marketing, either by the authoritiesor the companies themselves, although theHGC has recently published a further vol-untary Code of Practice.

In 2008, a Sunday Times investigationrevealed significant discrepancies in geneticrisk predictions provided to the journalist by23andMe, DeCode Genetics and the UKcompany Genetic Health.3 This report high-lighted that 'genetic information' is actuallyan interpretation of a DNA sequence thatmay differ substantially depending on whatis tested and the assumptions made. Theinvestigation covered not only tests beingmarketed DTC via the internet but also mis-leading claims being made about gene testssold via doctors in private healthcare clin-ics.4 An investigation of DTC genetic testsby the European Technology AssessmentGroup (ETAG) also raised serious concerns,including poor quality of information, lackof counselling and the testing of children.5

The leaders in the gene test market allremain loss-making companies, with a smallcustomer base, and DeCode Genetics hasdeclared bankruptcy.6 There is anecdotalevidence that, rather than being 'earlyadopters' in an expanding market, many oftheir customers may represent a clique oftrue believers—many working in the indus-try—plus the professionally curious (ethi-cists, social scientists, geneticists andjournalists), in a sea of more skeptical con-sumers who remain to be convinced.

Although these companies undoubtedlyhave customers in the UK and elsewhere inEurope, the market is likely to be a small frac-tion of the total number of tests sold. More

limited marketing efforts than in the U.S.,plus less consumer interest and trust in com-mercially provided health information, mayboth play a role.

However, there is also evidence thataccess to customers within the UK NationalHealth Service (NHS), via a public-privatepartnership would be attractive to manygene testing companies. In particular, com-panies are interested in accessing biologicalsamples for research purposes and some-including 23andMe-then advocate feedingback unvalidated research results to researchparticipants. There has been an ongoing dis-pute within the UK regarding the extent towhich DNA samples and electronic medicalrecords stored within the NHS might beaccessed for such research without consent.2Whilst the British public is supportive ofmedical research, there is little support forabandoning consent or for widespread data-sharing with commercial companies, whoare commonly presumed to be more inter-ested in profiteering than in improvinghealth. There are also significant privacyconcerns.

Role of publicly-funded health services

On the one hand, some policy-makersand advisors have argued that the publicly-funded NHS has a key role to play in driv-ing the supposed genetic revolution inhealthcare. From this perspective, the NHSis a unique resource to mine genetic andother healthcare data from the entire UKpopulation and make predictions regardinggenetic susceptibility to common diseases.In this vision of the future, DTC genetic testswould form part of a shift to a new systeminvolving greater use of public-private part-nerships in the NHS, including a major shiftto 'pre-symptomatic' treatment and the pos-sibility of individuals making top-up pay-ments for extra tests and treatments. Amajor expansion in the drug and healthcaremarket is expected as a result.2

On the other hand, many medical pro-fessionals remain skeptical of the value ofgenetic susceptibility testing and concernedabout unregulated DTC testing impactingon taxpayer-funded services by requiring


DTC Genetic Testing: A UK Perspective

BY HELENWALLACE

costly, time-consuming and medicallyunnecessary follow-up. The adoption ofmeaningless or misleading tests within theNHS itself is also likely to be resisted by pro-fessionals anxious to maintain standards ofcare as well as by the need to procure cost-effective public services. There is strong sup-port for only introducing tests which makea difference to health outcomes, i.e. whichwould alter advice or clinical management,or which significantly reduce uncertainty forpeople at high risk of a familial disorder.Until recently, this view was in conflict withpolitical pressures, particularly in the UK, tomove as quickly as possible to whole genomescreening of the general population on thegrounds that this would stimulate a newbiotech economy. However, economic real-ities and a change in UK government, com-bined with greater sensitivity to privacyconcerns, means that there is now less polit-ical enthusiasm for introducing innovationswithout assessing health outcomes and cost-effectiveness.

Thus, the debate about genetic testingwithin the EU is focused on protecting andimproving existing genetic testing servicesand preventing DTC tests from undermin-ing either these services or health servicesmore broadly.

The Eurogentest Network of Excellencewas funded by the European Commissionfrom 2005 to 2010 with the aim of estab-lishing harmonized, quality genetic testingservices in Europe.7 It has done much toimprove laboratory accreditation, surveyexisting services, involve patients and issueguidelines. A recent Eurogentest bookincludes extensive discussion of the need toevaluate the clinical validity, utility and costeffectiveness of tests.8 Whilst opinions onthe role of regulation vary, there is consen-sus on the need for such assessments beforenew tests are introduced into publicly-funded European health services. At thesame time, there is considerable skepticismthat tests for genetic susceptibility to com-mon, complex diseases—as opposed to testsfor rare disorders or predisposition to rarefamilial forms of common disorders—willprove of much clinical value.

A recent UK report, based on five expertworkshops, whilst recognising enormousprogress in genomic science, concluded that:“the importance of genomics for the pre-diction and prevention of common complexdiseases has been overestimated (thoughthere is little doubt about its potential to pro-vide a better understanding of disease mech-anisms).”9 The report found that genomicmedicine should focus on diagnostic and

cascade testing (screening family members)for single gene disorders and inherited sub-sets of complex disease, plus the use of spe-cific pharmacogenetic tests to predict andmonitor individual drug response. Thereport also advocated a media strategy“which focuses on 'myth-busting' (ratherthan creating further hype around genomics)without undermining research.”

Eleven professional genetics societies inFrance have gone further by issuing a state-ment criticizing the underlying theoreticalbasis for calculating risk of common diseasesbased on multiple genetic variants and con-cluding: “While genome wide studies pro-vide an essential contribution to scientificknowledge of multifactorial diseases, the iso-lated use of information provided by themlacks any capacity to predict future onset ofthose diseases. It leads to an erroneous per-ception of the risk for the individual.”10 Thisstatement reflects increasingly widespreaddoubts about the scientific basis of thisapproach to health.11 It is currently beingdiscussed within the European Soci-ety for Human Genetics (ESHG).

Although the value of pharmaco-genetic testing in specific circum-stances is widely recognized,European medicines regulators andclinicians have also preferred theapproach adopted by US medicalinsurers of waiting for more convincing datafrom clinical trials before such tests areintroduced: for example, in the context ofprescribing warfarin.12

Regulation and the single European market

Healthcare is the responsibility of theindividual member states of the EuropeanUnion, but the EU also creates a free mar-ket for the delivery of people, goods andservices, which requires the harmonizationof quality standards. In theory, standards forgenetic tests are covered by the In-vitroMedical Devices Directive (IVDD). How-ever, the IVDD is widely regarded as inade-quate, having failed to keep up withdevelopments in science, technology andmarketing, and is also interpreted in widelydifferent ways in different member states.One overarching problem is that genetictests are classified as 'low risk', meaning thatthe manufacturer has sole responsibility forensuring its own compliance and awardingitself the 'CE mark' that allows it to trade.In addition, some member states (especiallythe UK) interpret compliance as requiringonly demonstration of analytical validity, not

clinical validity. There is also a lack of clar-ity about whether genetic susceptibility testsare categorised as medical tests under theDirective, and about whether some labora-tory-developed tests should be covered bythe provisions. These difficulties of interpre-tation mean that even the self-assessment ofhealth-related genetic tests is lacking inmany cases. Thus, regulation is weaker thanin the U.S., where only laboratory-basedtests, not tests sold as manufactured kits,have escaped FDA oversight. The IVDD iscurrently undergoing a long process of revi-sion and a current consultation is seekingviews on these issues.13

In the meantime, legislation coveringgenetic tests has been introduced at thenational level in some countries (althoughnot the UK). For example, Germany hasestablished a commission to evaluate genetictests and requires counseling to be providedby a suitably qualified medical professionalunless the subject has waived the offer ofsuch counseling in writing.

The situation in Europe is further com-plicated by the role played by the EuropeanConvention on Human Rights and Biomed-icine, which was adopted by the Commit-tee of Ministers of the Council of Europe in1996 and opened for signature in Oviedo,Spain in 1997. The Council of Europe has awider membership than the EU: thirteenmember states of the EU have ratified theConvention, obliging them to ensure thattheir national legislation conforms to its pro-visions. An additional Protocol on GeneticTesting, adopted in 2008, has to date beenratified only by Slovenia, but includes impor-tant provisions requiring states to ensurethat genetic tests meet criteria of scientificand clinical validity, laboratory quality assur-ance and clinical utility, and that appropri-ate counselling is provided.14 Bringing theIVDD into line with the Protocol, as well aswith the OECD's Recommendations onQuality Assurance in Molecular Genetictesting, would allow a consistent approachto gene testing across Europe and protectconsumers from misleading claims.15 Thisapproach has been supported by the ESHGin its recent policy on DTC genetic tests.16


There is considerable skepticismthat tests for genetic susceptibilityto common, complex diseases will

prove of much clinical value.

Continued on page 24

Adele Schneider, MD, is Director of ClinicalGenetics at the Victor Center for JewishGenetic Diseases at Albert Einstein Health-care Network in Philadelphia. She wasinvited to speak at the July FDA hearings onconsumer genetic testing (statement printedat right).

Are very many direct-to-consumergenetic testing companies trying to tellpeople whether they are a carrier for Tay-Sachs?

Many of them are, because the test hasbeen around for a long time, it's a severe dis-ease, and people know about it. It fills allthe criteria for an important disease that youwould want to screen out of the community.The detection rate, if you do it with enzymes,is good. If you do both the enzyme and DNAtest, the detection rate is 98%; but if you onlydo the DNA, it's 88.6%. The DNA test islooking for specific mutations in the Jewishcommunity, but the Jewish community is notmonolithic—the demographics havechanged, so you can't just test the DNA.

And I assume none of these genetic test-ing companies have an option to includethe enzyme test?

The ones that are direct-to-consumer donot, because they're using saliva and theywould need a blood sample.

I haven't seen the results that they provide,but how do the companies only usingsaliva samples frame the results?

They say in the report that if you are neg-ative, your risk is reduced—they're carefulabout that. If you're a carrier, they tell youthat. What I'm concerned about is them say-ing your risk is reduced for Tay-Sachs whenit may not be, because they didn't do theproper test.

With enzyme and DNA testing, you'regoing to pick up 98% of the carriers. There'sthat 2% residual risk, at which point your riskis so significantly reduced that you prettymuch ignore it. If your residual risk is 25%,it means that one out of four people who wastold that their risk is reduced in fact doesn't

have a reduced risk. So it's important forpeople to understand, and to get counseling.

It's like if you had an X-ray and a beau-tician read it. You're not dealing with thepeople qualified to tell you about it—you'redealing with business people. If you look atthe staffing of many of these direct-to-con-sumer labs, their lab directors are not resi-dent lab directors and are often in other partsof the country. There is usually a PhD geneti-cist somewhere around, and the rest arebusiness people.

And there's the concern about conflict ofinterest …

Oh, there are a lot of conflicts of inter-est. All of these companies have people outthere who have good reputations, speakingon their behalf, who are on their payroll. Tothe person on the street, it looks great whena Harvard guy or a Yale guy says, “This is thebee's knees, we really love this test, it foundout that we were carriers.” That's great, butdoes this person really understand what theyare saying? And how many bucks are theybeing paid to say it?

You mentioned in your FDA statementthat you too often have been on the otherside of calls from people who orderedgenetic testing without seeking counsel-ing. Can you think of any examples thatstick out to you?

There was a woman who called us oneafternoon and said, “My doctor did my cho-lesterol and breast cancer gene testing andI'm positive. What do I do?” They had justsaid, “Let's get your cholesterol, and let's justget your breast cancer gene while we're aboutit.” No counseling. This is a woman whoselife is turned upside down, and there's no oneto explain it to her.

This happens all the time. Every geneti-cist has had to deal with something like that.And then we get the flipside: “My doctor did-n't look at my results and told me they werefine.” And they weren't fine.

You've had cases where the doctors did noteven look at the results?


False ReassuranceThere is cause for concern in the way DTCcompanies test for Tay-Sachs disorder

STATEMENT AND COMMENTS BY ADELE SCHNEIDER

ferent results is that we don't know how tocome up with a single net risk estimator fromthese variants. We just simply don't knowenough at this point.

One of the things that was left hangingafter the testimony was an idea that theindustry would love to have you believe: “Ifwe could all just get together and agree onstandards, it would be fine.” No, what wouldhappen is you would all agree on standardsand we would see the same risk predictionfrom all the companies …but that doesn'tmean it's correct!

How much of this do you think could besolved just by having a genetic counselorinvolved throughout the process?

That's part of the solution, that the indi-vidual who avails themselves of these testswould have a first responder who could givethem information. That probably isn't all ofit, though. As we learned from the GAOreport, people can get told all kinds of dif-ferent things, especially when there are con-flicts of interest that are swaying people togive certain kinds of advice.

If 23andMe would just have a line thatpeople could call, that would go a long waytoward alleviating some of my concerns. Butit doesn't relieve all of them, because I stillthink the claims that are being made in theiradvertising are simply wrong. And thatseems to me something that doesn't neces-sarily require further regulation; it requiresthe FTC to enforce truth in advertising.

Can I say one other thing that I didn't geta chance to say during my congressional tes-timony? One of the things you will hear fromthese companies at first sounds quite con-vincing. Cholesterol and blood pressure con-fer only subtle relative risks for heart disease;so they'll say, “High cholesterol only con-fers a 1.4 relative risk on somebody for aheart attack and this is similar to the degreeof risk conferred by genetic variants.” Andthat is true. But what they fail to discuss isthat your doctor doesn't check your choles-terol because they are primarily seeking pre-dictive information. Your doctor checks yourcholesterol because they can change yourcholesterol. They aren't doing it just so theycan say, “Oh, you're at increased risk for aheart attack. Have a good day.” They'rechecking it because they can do somethingabout it. And that puts it in an entirely dif-ferent category than these direct-to-con-sumer genetic tests.

The Broken ClockContinued from page 9

Adele Schneider, from a statement made at public meeting on oversight of laboratory developed tests,Sponsored by FDA, July 19-20, 2010:

Too often I have been on the other end of phone calls from a patient whose primarycare provider ordered genetic testing without providing genetic counseling and have hadto “pick up the pieces” under emergent conditions explaining to a distressed person whattheir test results might mean. I am concerned that companies offering direct-to-con-sumer testing are not necessarily obligated to obtain informed consent from customersor to include an appropriately trained medical professional in the testing process. As aresult individuals who are tested may not understand the test results, may take no actionwhen one would be beneficial and fail to take steps to prevent a problem. This might bea missed opportunity to provide good preventive care if the interaction bypasses the per-son's medical providers.

Some DTC companies test for the BRCA 1 and 2 mutations that occur at greater fre-quency in the Ashkenazi Jewish population, without counseling or adequate/meaning-ful informed consent. It is also possible for a minor to order testing from these onlinecompanies. Since the first principle of medical care is to “do no harm,” these practiceswould seem to be counter to the medical model of helping patients and not doing any-thing that might cause unnecessary distress or harm.

Laboratories offering DTC testing may expose the public to harm in several ways.First, the failure to provide adequate guidance in test selection and proper counselingabout the benefits and limitations of test results may lead to lack of recommendedmedical care or unnecessary medical care that would have been avoided if genetic coun-seling was part of the process. Test results provided by DTC companies are often notoffered in a format that the average individual can understand as was noted in an arti-cle in the May 2010 issue of Genetics in Medicine. Many do not provide a health pro-fessional to explain the results. Regulation is needed to ensure that the tests are reliableand clearly explained and results provided with the help of a medical professional.

Second, there are few laws that require DTC companies to protect the privacy orconfidentiality of consumer information, and some companies require consumers toconsent to the research use of their samples as a condition of testing. When IRBs approvea study using DNA it has to be clear what is done with the remainder of the sample. Sim-ilar consumer protection should be provided by labs offering DNA testing.

Third, the clinical utility of many of the tests on the DTC panels has not been estab-lished. Some panels have large numbers of tests with detection rates below 10%. Thatis not really a useful test but makes for good advertising (as in—”we screen for over 100disorders”) but this is not “truth in advertising” and is misleading the public. I would askthat regulatory agencies and perhaps the national medical organizations clarify whatdetection rate constitutes a valid test, so tests in these panels actually provide usefulinformation for the person tested. Finally, DTC test companies fail to disclose clear con-flicts of interest—such as the use of paid advisors as spokespeople without disclosingtheir financial relationships to the company on the website.

As the medical director of a Jewish genetic disease screening program I have a spe-cific concern relating to Tay-Sachs disease. Since the Hex A enzyme assay becameavailable in the 1970's over 1 million people have been screened for TS disease and theincidence of the disease in the Ashkenazi Jewish community has fallen by 90%. The opti-mal screen for TSD is an enzyme assay with the DNA test and this has a 98% sensitiv-ity. The enzyme assay has to be done on blood. The DTC companies are testing forTSD with DNA only (using saliva), looking at a small number of mutations that are knownto be present in a homogenous Ashkenazi Jewish population. With intermarriage andadoption, the AJ gene pool is no longer homogeneous and in a recent study we publishedin the American Journal of Medical Genetics, we showed that if you omit the enzymeassay you will miss 11.4% of AJ carriers who do not have one of the common AJ TSDgene mutations.

My fear is that members of the public, believing that they are obtaining good med-ical care, will be tested by one of these DTC panels and will be falsely reassured that theyare not TSD carriers when in fact their carrier status has been missed because HexAenzyme was not included in the assay. I fear that in the next year we will see an increasein births of babies with TSD to people who tried to get proper screening but instead weredeceived by a DTC company that failed to disclose that the TSD screening it providedwas inadequate to rule out TSD carrier status.


Yes. Babies get born with recessive dis-eases now and then where the mother wasscreened, the doctor told her she was fine,and when we go back and look, the resultswere positive. And the doctor says, “Youknow, I'm so busy—they're usually normal,so I assumed they would be normal.”

Is it a matter of it being difficult for doc-tors to interpret?

It's a matter of the doctor not being thor-ough. That's why genetic counseling is somuch better, because genetic counselors arethorough beyond words.

And they know exactly what they're look-ing for.

Exactly. And anybody who gets theirscreening done with a genetic counselor isgoing to know that the counselor double andtriple checks things.

Are you finding that more people aregoing to genetic counselors?

A little bit. In obstetric practices it'sbecoming somewhat more common, but stillmost doctors don't really know about geneticcounseling, and in places where you don'thave large medical centers, often there arecities that do not have a genetic counselor.Tulsa, Oklahoma doesn't have one, thoughthey're hiring one soon. There's a geneticistwho could do it, but it's not the same as liv-ing in Philadelphia or Boston where there arehundreds of genetic counselors.

23andMe is a personal genomics companybased in Mountain View, Cal. Anne Wojci-cki is co-founder of the company and Ash-ley Gould is 23andMe General Counsel.

Direct-to-consumer genetic testing hasreceived a lot of government and mediaattention recently. Are you satisfied withhow they have portrayed the industry andthe technology?

We believe that ultimately the attentionis useful in that we expect the industry toevolve and improve on the basis of construc-tive feedback. We think there is a good dealof misunderstanding of the technology weuse and our scientific processes. We havebeen working and will continue to work toset the record straight in this regard.

The recent GAO report on DTC testingwas highly critical of the industry andrecorded some eyebrow-raising conver-sations between fictional customers andrepresentatives from genetic testing com-panies, including 23andMe, and found anumber of accuracy problems. How doyou respond to the report's accusations?

The “eyebrow-raising” conversationswere not in fact related to 23andMe, butother companies in the DTC space. We sug-gest that anyone looking for the facts readour blog following the GAO report and con-gressional hearing. As our blog explains, wedo not agree with the accuracy accusations.Our processes have always been transpar-ent, and the bases for our risk estimates areno exception to this transparency.

In the wake of the GAO report, what newFDA regulations are you preparing for?How would you like to see FDA handleregulation of the DTC testing industry?

We are currently working closely withthe FDA and will provide updates as newdevelopments arise.

Do you believe consumers can generallyinterpret their DNA test results withouttalking to a genetic counselor or doctor?

Our data indicates that consumers are

quite capable of this, yet we are adata-driven company and there areongoing independent studiesassessing this question. Whenthese studies are published theresulting data, and data that is con-tinually collected, should provideadditional insight into this ques-tion. Our goal is for customers tounderstand what there is to knowabout their DNA; in this regard, asyou may know, in June of this yearwe launched the ability for our cus-tomers to contact independentgenetic counselors informed aboutour service. We look forward tolearning from published studiesand incorporating any changes thatwill improve customers' under-standing.

Why doesn't 23andMe includeconsultation with a genetic coun-selor as part of the 'Health Edi-tion' DNA testing service?

We believe an individual has the rightto decide if they would like to interact witha genetic counselor. As previously noted,in June we announced a partnership withInformed Medical Decisions, Inc., a nationalnetwork of genetic counselors.

How much clinical utility can really begleaned from results regarding healthconcerns with highly significant environ-mental components, such as heart dis-ease?

The answer depends on the report—aswe note that some reports have higher envi-ronmental components than others. Knowl-edge about genetics and its impact on healthis constantly evolving. We work to make thispoint very well understood in different ways,from our agreement with our customers not-ing risks and considerations in obtaining ourservice (See Section 5 of our TOS which ispresented to each customer and is on everypage of our website), to our online geneticsvideos. Contributing to the knowledge andunderstanding of the meaning of genetics

through our research was a large part of thereason 23andMe was founded. Despite theongoing understanding of many aspects ofour DNA, there are many well founded andwell accepted associations with publishedcorrelations to health conditions. Our objec-tive is to present our customers with whatscience can tell them about their DNA andprovide digestible context for that informa-tion.

What safeguards does 23andMe have inplace to prevent surreptitious testing?

The saliva collection device used by23andMe requires a sizeable sample that cantake anywhere from 5 to 20 minutes to col-lect. 23andMe also requires that each cus-tomer agree to specific representations,including that the saliva provided is theirown. To date, we have never received a com-plaint or logged a concern about surrepti-tious testing.


In Their Words: 23andMewith Anne Wojcicki and Ashley Gould

Is there a brief definition that you givepeople when they ask “what is a geneticcounselor?”

If I'm meeting somebody and they askme what genetic counselors do, I tell themthat genetic counselors work with familiesor individuals who are either at risk for orhave a genetic condition, we take their fam-ily and medical histories, and we help assesswhat their chances are for that condition; wego over whether there are tests available andwhat is good and bad about that testing; andif there is a diagnosis, we explain what itmeans and connect them with the supportthat they need, whether it be medical pro-fessionals or a support group.

Are there certain scenarios when youwould tell someone not to get a test?

If someone doesn't have a history thatwould predispose them to a condition, wereally want to understand their reasoning forgetting a test for it. Part of it is a matter ofspending our health care dollars wisely.Obviously if someone wants to pay for it outof pocket, understanding that this informa-tion may not be as impactful as they werehoping, that's one thing. The more typicalscenario genetic counselors deal with iswhen we are billing insurance, so we haveto be careful to consider whether someonereally has a risk that justifies using healthcare dollars to assess it.

The second part of it is the psychoso-cial element. If somebody really wants tohave testing done, we want to ask them somequestions about why, and why now? I had apatient who wanted to be tested for Hunt-ington's disease six months before she wasgetting married. It was totally medicallyappropriate—her father had been affected—but she was six months from getting mar-ried, so I asked her: Why now? Would thischange anything for you? And after that dis-cussion, she thought about it and decidedthat now wasn't the time.

A good deal of attention has been drawnto direct-to-consumer genetic testingrecently on Capitol Hill, from the GAOreport to FDA and congressional hear-ings. Do you think the attention is steer-

ing the conversation in the right direc-tion?

I think the positive thing that's comingout of all of this is that it's engaging people.I believe that more consumers and morephysicians are aware of the availability ofgenetic testing, and I hope that they arelearning about some of the possible benefitsand drawbacks of obtaining genetic infor-mation. So I see that as a positive outcome.Genetic counselors work primarily withpatients and obviously we care a lot aboutpeople having access to genetic information,so a real benefit that has come out of thisfor patients is that they probably are moreaware and might be more likely to inquireabout genetic testing to help them.

From the NSGC's perspective, I think itis most important for people to know thatthey have the opportunity to meet with agenetic counselor before they have testing,to determine if testing is right for them, tofind an appropriate test, and to have supportinterpreting the results if they decide to havetesting. So the benefit of all this is that itstarted a conversation, and I see that as fun-damentally a good thing.

Do you find that many customers ofdirect-to-consumer genetic tests are com-ing to genetic counselors first?

There has definitely been an increase inrecent inquiries, but I don't know whether ithas been more frequently before or after thetest. I certainly know of situations wherepeople have contacted genetic counselorsafter the fact.

One example is a woman who'd had car-rier testing for a number of genetic disordersand was found to be a carrier of Alpha-1antitrypsin deficiency, a condition whichresults in early lung problems and basicallycauses emphysema even if the person is nota smoker. You have to have two copies ofthe gene in order to be affected, and this indi-vidual had only one copy. She had not hadany genetic counseling beforehand, and shecalled the genetic counselor in a panic andthought that she was at risk for the condi-tion.

So the report wasn't clear about the dif-

ference between being a carrier and actu-ally being at risk for the condition?

Exactly, so she thought that being a car-rier would mean she could be affected bythose symptoms. It's an example of the valueof meeting with a genetic counselor before-hand. A genetic counselor will ask why youwant to have the test, go over which tests areright for you, and explain what you can learnand what you won't learn from it. If you stillwant to go ahead, that's fine, and you alreadyhave a relationship with that counselor andcan call them up right away and go throughthe results and not have to go through thatperiod of panic.

Would you be concerned about a conflictof interest if customers go to a counseloron the DTC testing company's payrollinstead of an independent genetic coun-selor?

I think it's obvious there's some inherentconflict of interest. That doesn't mean thatsomeone who is a board certified geneticcounselor who works for a company can-not provide good care to a patient, but it'simportant to look at the incentives and howthose counselors are evaluated … but I thinkit's fair to say there is some potential inher-ent conflict of interest, and patients couldavoid all of that if they contact a geneticcounselor who is not affiliated with the com-pany.

Is there a best practice scenario you canpoint to where genetic counselors areworking together with test providers toreach the best outcomes for patients? Isthere a model already in place?

If you look at more classic genetic test-ing—testing for single gene disorders likecystic fibrosis, sickle cell, and Tay-Sachs dis-ease—a lot of laboratories work with therequirement of having a provider involvedand they have close relationships withgenetic centers. For example, academicallybased labs will often have a genetic counselorbased in the lab, primarily to get in touchwith a provider if something doesn't lookright. For instance, there may be a questionas to whether the patient is really orderingthe right test, and those genetic counselors


Genetic Counselors: Don’t Get Tested Without OneAn interview with Elizabeth Kearney, President of the National Society of GeneticCounselors

DNA provides a rich digital source ofmedical information; as a result it has greatscientific value. But it is also ripe for datasharing and has significant commercial valueas well.

Purchasing genetic testing services in anonline commercial marketplace raises sig-nificant privacy concerns, as consumers mayturn over their DNA and other personallyidentifiable information to companies with-out a clear understanding of the privacy risksand without clear guidance as to their legaland regulatory rights in this area.

There are currently no clear guidelineson the ownership of genetic material and theinformation derived from it, nor are thereclear guidelines with respect to the protec-tion of customer privacy by the direct-to-consumer genetic testing industry. Indeed,consent forms and privacy policies varywidely within the industry and without stan-dards can be unclear and often subject tochange.

There are three specific areas where sig-nificant privacy concerns arise:

1) Controls on DNA Submitted by Customers

Current practices related to ensuring thatcustomers are submitting only their ownDNA are insufficient. At present, commer-cial personal genomics companies do requirecustomers to confirm they have the legalauthority to submit DNA samples, yet suchstatements are not clearly and conspicuouslyposted but rather often hidden within largerprivacy and consent documents which areoften visible to the consumer only after theregistration process has begun. Moreover,they do not explicitly warn customers of thepossible issues raised by submitting anotherindividual's DNA for analysis.

Considering how simple surreptitiouscollection of individual DNA can be, it is nothard to imagine how political, social and per-sonal motivations could compel theimproper submission of DNA samples. This

is a particular concern since most of thesecompanies allow for an individual to pur-chase multiple testing kits per order. Yet, fewcontrols are offered beyond such statementsto ensure that customers are actually com-plying with this requirement. No offer ofproof is requested beyond the statement.This could easily be included as part of thesample submission process.

2) Security of Genetic Information

Customers are often not limited to pro-viding a DNA sample as part of their par-ticipation in the personal genomicsmarketplace. They are also offered a varietyof surveys, blogs and other tools where theycan provide personally identifiable informa-tion. Whenever identifiable DNA samplesare collected and stored, there is a high riskthat violations of genetic privacy will fol-low. The methodology by which this infor-mation is secured is essential, yet withoutstandards and oversight we still know verylittle beyond the assurances of the industryas to what specific controls are used.

Moreover, the privacy policies of DTCcompanies are not subject to the health pri-vacy regulations issued pursuant to theHeath Insurance Portability and Account-ability Act (HIPAA) and there few state andfederal privacy laws that apply. It is essen-tial that personal information should be pro-tected by security safeguards appropriateto the sensitivity of the information.

Safeguards should include physical, tech-nical and administrative measures to protectinformation and biological samples fromunauthorized access, use, disclosure, alter-ation or destruction.

Almost all DTC company privacy poli-cies make statements about security safe-guards, though the degree of detail variessubstantially. Mistakes and other breachesof security are not uncommon. Just this sum-mer, the DTC company 23andMe acciden-tally sent data of up to 96 individuals to thewrong customers.1


DTC Genetic Testing: Consumer Privacy Concerns

BY JEREMY GRUBER

who work in the lab might get back in touchwith whoever ordered the test and advisethem about whether this is the test that theyreally want. In this model the genetic coun-selor is in a sense the gatekeeper for theappropriateness of testing.

Is there any particular trait or set of traitsbeing routinely oversold in terms of util-ity for patients? Put differently, is there atest or area of testing where you think agenetic counselor is most needed?

One of the areas of concern is whensomeone is ordering the wrong test. Oneproblem is simply that ordering the wrongtest is a waste of money; but the more signif-icant concern might be around not integrat-ing information from genetic testing withmedical and family history.

I would use diabetes as an example. Sup-pose somebody has a family history of dia-betes and they are wondering about theirown risk of developing diabetes, and theyhave a test result that shows they havedecreased risk over the general population—but they have a family history of diabetes,and maybe it's even a woman who has hadgestational diabetes during a pregnancy. Agenetic counselor would look at all of thatand integrate it, and tell that patient thatwhile the test result was reassuring, mostlikely the genetic factors responsible for thediabetes in your family are not those thatwere tested in this particular test. That's anexample of when a test is misinterpreted asbeing sufficient information on its own,when you really want to integrate it withfamily and medical history.

Has the profession of genetic counselingchanged as more direct-to-consumergenetic tests have been introduced?

Actually, I don't think that the practiceof genetic counseling has changed that dra-matically. The model for how we care for apatient is the same whether we're testing forsingle gene disorders or whether a patientis coming to a genetic counselor with areport from a direct-to-consumer lab. I alsothink that it's a pretty small percentage of thepopulation that's pursuing direct-to-con-sumer testing without the provider involved.So I really don't think that, as of yet, it hasinfluenced the practice of genetic counsel-ing very much.

certainly not expressed to customers.Most DTC companies do not ask for spe-

cific consent for these purposes. Some com-panies are moving in the right direction.23andMe has recently begun asking for spe-cific consent for participation in publishedresearch. However, they note that even byrefusing to participate,

we may still use your Genetic and/orSelf-Reported Information for R&D purposes…which may include disclo-sure…to third-party non-profit and/orcommercial research partners who willnot publish that information in a peerreviewed scientific journal.3

The degree to which these types of part-nerships and others have proliferated withinthe industry is still largely unclear. What isclear is that it is essential that affirmativewritten consent must be required beforeDTC companies can use any customer gen-erated genetic information in this way.

There is currently very little guidance onhow consumers can protect their privacy.For example, the US Federal Trade Commis-sion gives the following advice to consumerswho are considering DTC genetic tests:

Protect your privacy. At-home testcompanies may post patient test resultsonline. If the website is not secure, yourinformation may be seen by others.Before you do business with any com-pany online, check the privacy policyto see how they may use your personalinformation, and whether they sharecustomer information with mar-keters.4

Such advisories are hardly satisfactory toensure consumer privacy is protected.

It is essential that Congress, the Food andDrug Administration, the Federal TradeCommission, and the Centers for DiseaseControl all work together to help set privacystandards for the direct-to-consumer genetictesting industry and ensure that all issuesregarding industry practice are adequatelysupervised to ensure compliance.

This essay is a modified excerpt from testi-mony offered at the FDA public meeting on“Oversight of Laboratory Developed Tests'Direct to Consumer Genetic Testing'” in Sil-ver Springs, Maryland on July 20, 2010.

Jeremy Gruber, JD, is the President of theCouncil for Responsible Genetics.


There is also no transparency as to thedegree to which personally identifiablehealth information is de-identified. As theability to share, store, and aggregate genomicdata progresses, the capability of keeping thisdata anonymous becomes increasinglyimportant. Because an individual's geneticinformation is so personal and specific, it isvital to protect it from any unwarrantedaccess or use. There have been severalinstances where de-identified data has beenre-identified and personal informationlinked back to its owner. One such study2achieved re-identification of DNA data andestablished identifiable linkages in 33-100%of surveyed cases, which focused on eightgene-based diseases. The researchers usedanonymized DNA database entries, andrelated the information to publicly availablehealth information despite the fact that thedatabase did not include any explicit iden-tifiers, such as name, address, social securitynumber, or any other personal information.Because not all de-identification techniquesadequately anonymize data, it is importantthat the process employed by the industryis robust, scalable, transparent and shown toprovably prevent the identification of cus-tomer information.

3) Third Party Disclosure of CustomerData

One significant unresolved issue relatingto the DTC industry is exactly who owns thecustomer's data. Most DTC companies donot explicitly address this issue in their pri-vacy policies. If the DNA sample and otherinformation submitted by the customer arethe property of the company, the companyis free to sell or otherwise transfer that infor-mation to a third party.

Many DTC companies have adopted thisapproach as part of their business modelwithout sufficiently explaining to customersthe extent to which this may occur, what typeof data is being transferred and the potentialnegative consequences. For example23andMe has partnerships with the Swissfirm Mondobiotech and the Parkinson'sInstitute and Navigenics is conducting stud-ies with the Mayo Clinic and Scripps Insti-tute.

Moreover how such information is to betreated upon sale of a company or if a com-pany enters bankruptcy proceedings, partic-ularly when the entities potentially acquiringsuch information have significantly less strictprivacy standards, is less than clear and is

We will dispense with the starry heavens andso convert to right use from uselessness thatnatural indwelling intelligence of the soul.1-Plato, The Republic

In his forthcoming book, The $1,000Genome, Kevin Davies casts an uncriticalgaze at corporate biotechnology, offering lit-tle more than a protracted puff piece onspeculative technology. He populates hisnarrative with the leading lights of thatindustry, celebrating their innovation andavarice in equal measure. Davies's dramatispersonæ—reading like a Who's Who of thebiotech industry—is almost exclusively com-prised of “life sciences” entrepreneurs andtheir pet firms. Throughout, his haphazardstyle elides these market participants withthe market discourses each produces, pro-moting the view that they are all one in thesame feature in the production of a “person-alized” biomedical future. The future of bio-medicine has its enemies, however, and firstamong them are pseudojournalistic parti-sans who think their love of biotech cap-ital translates into some kind ofknowledge. The $1,000 Genome is muchlike the “personal” biotechnology indus-try it chronicles, ultimately looking tocapture market share in the name ofhealth and market genetic misinforma-tion in the name of truth.

Davies offers the telling story ofJonathan Rothberg, founder of CuraGenCorp., 454 Life Sciences Corp., Ion TorrentSystems, Inc., Clarifi Corporation, and Rain-Dance Technologies Inc. Rothberg—DNAsequencing pioneer and architect of hun-dred-million dollar profits—is also the fatherof a child born with tuberous sclerosis, ahereditary condition in which the brain, skin,and major organs become covered withsmall tumors.2 Faced with his daughter's ill-ness, Rothberg's “typically audacious”response was to found the Rothberg Insti-tute for Childhood Diseases, “a non-profitorganization dedicated to finding a cure forchildren suffering from Tuberous Sclerosis.”3

In addition to his foundation, at hiseleven-acre ocean-side home Rothberg alsocommissioned the mammoth Stonehenge-

like sculpture entitled the “Circle of Life.” Hebuilt it “for [his] kids,” Davies writes, “as if itwas [sic] entirely routine to import 700 tonsof Norwegian granite and sculpt, polish, andarranged it according to celestial factors onone's own oceanfront property.”4 The giantstones are arrayed according to the birthdaysof Rothberg's children as well as other astro-logical “events.” “Think of the Circle of Lifeas a complex watch,” its creator Darrell Petitis quoted in Stone World magazine, which“demonstrates that these structures canfunction as powerful astrological instru-ments with substantial predictive abilities.”5

Rothberg's sculpture is like Rothberg'sfoundation, which is like any of Rothberg'sbiotechnology companies—all of which arelike Rothberg himself: a perfectionist“biotech impresario” who neverthelessreminds Davies of “a boy trapped in a man'sbody.”6 Whether intentional or not, thisinsight captures the doubly-capricious ide-ology that unites Rothberg and his biotech-nology businesses and that is metaphorically

expressed in his sculpture the “Circle of Life,”namely: that DNA can be thought of as “acomplex watch” that, upon the expenditureof adequate capital, can “function as a pow-erful ... instrument with substantial predic-tive abilities.” In other words, human traitsand diseases can be analytically reduced togenetic causes. Davies shares this mislead-ing misperception. “[M]ost human disease... such as heart disease, diabetes, obesity, andcancer,” he writes, are “caused primarily bycommon DNA variants.”7 Naïve at best, thisessentialist view of genetics—a kind ofgenetic astrology—is the tacit assumptionlying behind the characters and companiesDavies chronicles.

“Genetics isn't just a science,” Barbra Katz

Rothman argues in her book Genetic Mapsand Human Imaginations, “[i]t's a way ofthinking, an ideology.” “We're coming to seelife through a 'prism of heritability,'” shewrites, “a 'discourse of gene action,' a genet-ics frame.”8 It is in this “genetic frame”—with promises of horoscopes spun fromstrands of DNA—that direct-to-consumer(DTC) genetic firms like 23andMe, Navigen-ics, and deCODEme deploy genetic astrol-ogy as a marketing strategy. “When you goto a bar,” Davies quotes Linda Avery, co-founder of 23andMe, “the pickup line couldchange from, 'What's your sign?' to 'What'syour haplogroup?'”9 Kari Stefansson,deCODEme co-founder and ExecutiveChairman, describes his company as provid-ing “a service where people . . . are comingto us to learn more about themselves.”10 Ofthe two men behind Navigenics, DietrichStephan dedicated fifteen years of research“predicated on the belief that all human dis-ease had a genetic component”11 and DavidAgus “believes it will come down to ... gene

X is up, gene Y is down.”12 “Know yourCODE,” Stefansson is quoted at the apexof his sales pitch: “[l]earn more about yourancestry, traits, and health risks.”13 Inshort: know yourself by knowing yourgenes.

As stone monuments and tabloidback-pages the world over attest, predict-ing the future is a seductive business.Moreover, the discourse situating those

predictions in DNA is not new. In 1995Dorothy Nelkin and M. Susan Lindeeobserved that “images and narratives of thegene in popular culture reflect and convey .. . genetic essentialism.”14 Then, as now,“genetic essentialism” represents a mode ofbiological reductionism resting on the fal-lacy that “reduces the self to a molecularentity, equating human beings, in all theirsocial, historical, and moral complexity, withtheir genes.”15 In other words, “[g]eneticessentialism is the idea that the essence, thenature of a human being is defined by itsgenes.”16 The mass appeal of genetics,Nelkin and Lindee conclude, “lies partly inits image as a predictive science: a means touncover predispositions.”17 It is precisely


The $1,000 Genome: Caveat EmptorBY ANDREW D.THIBEDEAU

The future of biomedicine has itsenemies, and first among them arepseudojournalistic partisans whothink their love of biotech capital

translates into some kind of knowledge.

this image of genetics as horoscope that DTCcorporations purposefully invoke. But in thesearch for meaningful predispositions, itbecomes increasingly easy to collapse thedistinction between statistical correlationand factual cause. The subtle but significantdifference between the two is lost on Davies,who spends most of The $1,000 Genomeplaying interlocutor to corporate biotech—rarely if ever interposing critical distancebetween biotechnology marketing and hisreader. One can only conclude that Davies'senterprise is not, as he claims, to documenta genomic revolution, but instead to sell aparticular narrative in which venture-capi-tal biotech is savior to client and shareholderalike. The ease with which Davies allowsessentialist discourses to dominate his sub-ject matter belies his unambiguous predis-position toward industrial biotechnology,calling into question the merit of his entirework.

Davies asserts that the DTC genetics isabout patient “empowerment” and “person-alized” healthcare. Navigenics, deCODEme,and 23andMe all offer services that their fin-anciers believe “will become part and par-cel of twenty-first-century medicine.”18Accordingly, a 2010 report of the Govern-ment Accountability Office found that thewebsites of these three corporations “con-tain a variation of the statement that their

tests help consumers and their physiciansdetect disease risks.”19 In a series of pro-tracted vignettes profiling various players onthe biotech stage, Davies invokes geneticastrology in all but name as he recounts theservices they offer. 23andMe “provide[s] thedeepest dive into the genome,” he writes,“presenting information on ancestry, traits... carrier status for Mendelian disorders, andrisks for common diseases.”20 “The basicgoal,” he quotes Stefansson, “was always touse genetics for preventative health care.”21Navigenics also “focuses squarely on riskassessment for actionable, common medicalconditions such as heart disease, cancer, anddiabetes.”22 Davies's text documents yetdenies how these firms traffic in medicalprognostication.

Hence Davies reproduces the proclama-tions of DTC biotech, decrying any sugges-tion that their services are medical orpredictive. “From the inception of the con-sumer-genomics industry,” Davies assureshis reader, “every piece of marketing collat-eral, Web site real estate, and legal documentbearing a company logo stressed and reaf-firmed the strictly educational, nondiagnos-tic nature of their genome-scanningservices.”23 It is impossible to interpret thisclaim—by the DTC industry or by Davies—as anything but disingenuous. After con-ducting a clandestine investigation of fifteenDTC genetics firms, the GAO found that tenof them “engaged in some form of fraudu-lent, deceptive, or otherwise questionablemarketing practices.”24 What sort of fraud-ulent practices? “Advertising for genetic test-ing on TV, in print, on the radio or via theinternet,” a recent British study concluded,“provide[s] simplistic explanations of genet-ics and exploit[s] existing anxieties and wide-spread misinformation about geneticdeterminism.”25 A paper published in 2008in the Journal of Business Ethics identifiesthe same trend: “there has been a tendencyon the part of many diagnostic companies todownplay the probabilistic nature of geneticinformation and to use deterministic lan-guage in their physician- and patient-ori-ented advertising and promotionalcampaigns.”26 Davies writes in the samedeterminist language, conflating cause andcorrelation without regard for the myths hethereby endorses.

And what of the medical utility of DTCgenetics? “The test results we received,” theGAO investigation concludes, “are mislead-ing and of little or no practical use to con-sumers.”27 23andMe Director Ester Dyson,quoted by Davies, agrees: “[i]t's fascinating.

But medically useful? No.”28 One wonderswhat role useless genetic tests have to playin “the new era of personalized medicine.”Remaining silent on this question, Daviesmaintains a legitimating façade of “personal”genetic knowledge; this is a paradox on theface of his text that irretrievably indicts itsultimate claim to legitimacy. In the same way,heeding well their legal counsel, every DTCmarketing campaign is flush with fine printceaselessly working to negate any claimsmade elsewhere. The DTC market thatDavies describes is a contradiction: “[t]heexplicit health claims and the small print dis-claimers cannot both be true.”29 Again,Davies fails to register what other observerssee plainly. Occupying a nether regionbetween naïveté and complicity, Daviesaccepts DTC's talking points sans reflection,parroting them back at his reader. As such,his book is more akin to biotech puffery thanexplanatory prose.

The (pre)dominance of deterministicrhetoric in the public discourse surroundinggenetic testing is worrying not simplybecause it is bad science. According to a 2010study, “[p]ublic understanding of details per-tinent to genetic testing generally appears tobe weak.”30 In this context, appeals togenetic essentialism in DTC marketing mustbe understood as intentionally misleading.“Like its competitors, “ Davies neverthelessclaims, “Navigenics ... makes a good effort tocommunicate the dual role of genetics andenvironment ... in shaping individual risk ofcomplex diseases.”31 If this were so, it is cer-tainly not reflected in their advertising,where disease “is portrayed as a unitary phe-nomenon, something that can be resolvedby genetic testing and appropriate medicaltreatment.” Thus a return to Jonathan Roth-berg's seaside Stonehenge: the center of grav-ity for both DTC genetics and The $1,000Genome is the myth of the genetic horo-scope. Fine print aside, Navigenics and itscompetitors are “exploiting a climate ofgenetic determinism and public anxiety tosell speculative technologies.”32 The $1,000Genome's myopic stance toward theseaspects of its subject signals its ultimate fail-ing. In the end, Davies is less concerned withthe revolution of “personalized” medicinethan he is with the astrological edifice con-structed by those financial interests investedin the predictions of that revolution.

Andrew Thibedeau, JD, is Senior Fellow atthe Council for Responsible Genetics.


The $1,000 Genome: The Revolution inDNA Sequencing and the New Era ofPersonalized Medicineby Kevin Davies. Free Press (2010)

In the March/April 2010 issue ofGeneWatch, Beth Willis of Frederick Mary-land stated:

We also know that high containmentbiodefense lab proliferation is a nationalpolicy problem that has to be addressedin Washington.

As the director of a Biosafety Level Three(BSL3) laboratory at a large academic med-ical center, I thought it might be useful toGeneWatch readers to hear some commentsfrom the inside of one of those laboratories.I will describe our efforts to build a safe andcollaborative environment in our contain-ment laboratory, and the impact of increasedregulations following the anthrax attacks andPATRIOT Act on our procedures.

Our respiratory infectious agent programwas begun in 1999 with the construction ofnew Biosafety Level three containment spacewithin existing laboratory space in ourresearch building as part of the Center forEmerging and Re-emerging Pathogens(CERP) at UMDNJ-NJMS. The laboratorywas designed for the study of the causativeagents of tuberculosis and HIV-AIDS. Theinitial application was submitted before theyear 2001, which was followed by unprece-dented regulatory oversight. However, wehad formed close ties and collaborations withthe Emergency Response and Biosafety per-sonnel at the university during the process ofdesigning the lab.

Soon after opening in 1999, we receivedadditional funding for work with bacterialand viral agents, some of which were consid-ered potential biological weapons agents;such microbes are now termed “SelectAgents.” Consulting with our colleagues insafety and security, we instituted new proce-dures in the form of training programs andsafety procedures. For example, we felt it wasessential for safety reasons that two peoplebe present at all times during work with dan-gerous pathogens such as Bacillus anthracis(anthrax) and Yersinia pestis (plague): we rec-ognized that people can be tired, be dis-tracted, make mistakes, and that having twopeople carrying out the experiments wouldserve as a internal check for errors and to pre-

vent accidents. This “two-person rule” waslater required to ensure security of thereagents, discussed below.

During the months immediately follow-ing the 2001 anthrax attacks, the scientificcommunity saw a gradual increase in regu-lations and oversight for Select Agent work,mostly in the form of increased security andaccess control. The impact of these new ruleswas discussed in Dias et al, 2010[1], and alsoreviewed by Andrew Thibedeau in theMarch/April 2010 issue of GeneWatch. Fur-ther debate of the impact and efficacy of theseregulations is outside the scope of this arti-cle. Note however that there are few differ-ences in procedures between working withTB and anthrax in our laboratory.

Traditional lab safety and bloodbornepathogen training, mandated by the Occu-pational Safety and Health Association(OSHA), is provided to all laboratory work-ers. OSHA has identified within its array ofstandards for general industry those withspecific application to laboratories, such aschemical safety/”right-to-know”, hazardouswaste and regulated medical waste handling,fire safety, personal protective equipment,and emergency procedures. The formats fortrainings in many institutions are slides andlectures with a short quiz, but we wanted amore hands-on approach for our BSL3 safetytraining.

However, following the model of emer-gency responder training methods and withthe involvement of our first responder col-leagues, in 2002 we began to develop a seriesof exercises to test the efficacy of our train-ing modules. These exercises range fromtabletop format to full-scale scenario exer-cises involving representatives of depart-ments and agencies at the level of theinstitution, the city, the county, and the State.We have as many as 100 people attending ourexercises, both players and observers.

Experienced first responders are well sea-soned in carrying out training exercises. Wefound that scientists and laboratory work-ers were unfamiliar with the format and pur-pose of an emergency response trainingexercise. The scientists felt anxious about thepossibility of error. Many scientists are per-fectionists and they struggled with the stress

of thinking that everything had to go exactlyright. They were often defensive and some-times critical of their colleagues. They werealso unfamiliar with the incident commandsystem procedures that drive emergencyresponse to incidents such as those thatmight be experienced at our laboratories. Sowe learned to prepare them beforehand forhow these exercises work, pointing out thatthey are designed to instruct us in what wedo not yet know, and to discover what mightnot work. Our BSL3 staff are now requiredto complete awareness level incident com-mand training (FEMA course ICS 100). Theexercises are followed by long discussionsthat analyze in detail where the problems lieand what the solutions might be. After thefirst full-scale exercise, a real emergencyoccurred. A pressurized water pipe burst dueto extremely cold temperatures on a Satur-day evening, resulting in at least 6 inches ofwater in the BSL3 and throughout the CEP.The previous exercises helped staff torespond calmly to this crisis, without panicor confusion, allowing them effectively tocarry out emergency procedures in this off-hours emergency. Similarly, we experienceda regional blackout, and the response to thiscrisis also went fairly smoothly.

We hold frequent “refresher” trainings toreview protocols and introduce modifica-tions that might be required by changes inCDC regulations. For our twice-yearlyreviews, we have changed the format of thequizzes, created games and asked partici-pants to lead discussions. All members of thelaboratories, from staff workers to the Prin-


A View From the InsideEstablishing and maintaining a Biosafety Level Three laboratory

BY NANCY CONNELL

cipal Investigators, are involved. We held ahands-on demonstration for aerosol creationusing fluorescent marker dyes so users couldanalyze their own technique. We haverecently instituted an entirely new format:initially and once per year thereafter, theBSL3 manager and institutional biosafetyofficer will follow and observe each user ass/he carries out a protocol, including entryand exit procedures.

Finally, and perhaps most importantly,we strive to create a supportive atmospherethat leads to a secure and collaborative envi-ronment. In a punitive environment, there isthe chance that an accident will go unre-ported; this is a most dangerous situation. Itis essential to create an environment whereif a mistake is an honest one, people trust thatthey will not be punished, be restricted fromaccess to their experiments, lose their jobs orworse.

Security training

It was in the wake of the World TradeCenter attacks and the anthrax letter mail-ings that security became an enormous issuein academic laboratories such as ours. Allworkers must comply with the terms of theUSA PATRIOT ACT (Uniting and Strength-ening America by Providing AppropriateTools Required to Intercept and ObstructTerrorism Act of 2002) and other legislation(Public Health Security and Bio-terrorismPreparedness and Response Act of 2002).“Personnel reliability”, as regulated by thisand other legislation, has had an ever-widen-ing effect on the process of science. The earlyand close relationship between law enforce-ment and our facility meant that in an oper-ational sense, many security procedures wereincorporated into the procedures in our lab-oratory from the very opening of the pro-gram. First and foremost, researchers mustnow be fingerprinted and submit to a back-ground check by the Department of Justicebefore handling or accessing select agents.All refrigerators and incubators have locksand pin numbers, with two-person access.Most importantly, there are inventoryrequirements for Select Agents, so that sam-ples are tracked from seed stocks and work-ing stocks, accounting for every microliter ofculture. Lab notebooks are always vital forresearchers, but tracking agents and tubesis important to be sure there has not been atheft of an agent. If an inventory status can-not be resolved, and does not match the lab-oratory notebook, then that incident istreated as a theft, which requires reportingto the FBI and CDC. This type of reporting

was new to scientists, and in the beginningthere was no guidance as to the best way torecord all this data. Inventories can add in alayer of anxiety in order to be sure that thingsare logged properly, since the repercussionscan be severe. Now, several years after theintroduction of inventory requirements,guidance has been given as to the preferredmethod of data recording, and many labo-ratories, including ours, have developed asystem to reduce the time burden of this reg-ulation. Note that this kind of oversight andtracking is modeling on the tracking of radi-ological material and its utility for replicat-ing organisms has been questioned by manyscientists (Casadevall and Imperiale, 2010).

Ethics, dual use and responsible conduct

Massive increases in funding over thepast decade— over $50 billion between 2001and 2009—have been directed towards civil-ian biodefense (Franco, 2009). An enormousamount of federal effort and capacity is nowdirected towards select agent research in par-ticular and infectious disease research in gen-eral. The global proliferation of BSL3containment laboratories has sparked safetyand security concerns and is reflected inincreased oversight of laboratory operations,as discussed above. Additionally, the conceptof dual use research is receiving increasingattention around the world (Selgelid, 2009).Dual use research of concern is research thatis conceived for the purpose of healing orhelping human kind but which can be usedin the development of dangerous technolo-gies for malevolent purposes. Our researchprogram focuses on bacterial Select Agents,and the experiments we perform with theseorganisms are intrinsically dual use, in viewof their potential—and in some cases, histor-ical—development as bioweapons.

Over the past fifteen years at our insti-tution, we have developed a number ofavenues for introducing the concept of dualuse research to the university community(Connell and McCluskey, 2010). The first isthrough the federally mandated “Responsi-ble Conduct of Research” education ofNational Institute of Health (NIH)-spon-sored trainees . The second route is throughthe Institutional Biosafety Committee, orig-inally mandated by the NIH in the 1970's toreview experiments involving recombinantDNA and since expanded to include infec-tious agents. The third avenue is the labora-tory safety training mandated by theOccupational Safety and Health Associationfor all laboratory workers. The fourth routeis through a robust biodefense “certificate”

academic curriculum, open to all students atthe university regardless of program (PhD,MS, MD, nursing, etc). We are in the processof designing and implementing a fifthapproach using an institutionally based“train-the-trainer” system of intercalatingdual use awareness into individual academicdepartments through periodic seminars anddiscussion groups. Of course, there is someapprehension in the scientific and securitycommunities that identifying inherently orpotentially dangerous research will have thenegative effect of directing attention to pos-sible “recipes.” In other words, increasingawareness of potential dangers might lead,paradoxically, to the actual creation of suchperils. These and other debates in the field ofdual use ethics (Rappert, 2007; Segelid, 2009)are beyond the scope of this discussion, butmost would agree that scientific inquiry andits dissemination must be allowed to con-tinue.

Conclusion

The transition from basic microbiologylaboratory to biocontainment laboratory is acomplex process of learning new regulations,increased training and responsibility, andincorporation of new practices and proce-dures. Maintaining a containment laboratoryis an ongoing process: regulations change andsecurity requirements differ among fundingagencies, but most importantly, we recognizecontinuous monitoring in emergencyresponse and safety training in an emotion-ally safe environment. As the biomedicalresearch enterprise becomes increasinglycomplex with regard to policy and regulation,the Biosafety Officer plays a pivotal role,coordinating the needs of the workers, therequirements of the regulatory agencies andthe needs of the institution. In turn, the coop-eration of the PI with the biosafety officer isalso vital; the PI can set the atmosphere forthe laboratory and can also foster in post doc-toral fellows, technicians, and students anappreciation of the delicate balance of con-ducting good scientific experiments in assafely as possible. This balance between thescientists and the regulatory personnel isinstrumental in developing a successful andsafe Select Agent research program.

Nancy Connell is Professor in the Depart-ment of Medicine at New Jersey MedicalSchool, Director of the Biosafety Level ThreeFacility of the university’s Center for the Studyof Emerging and Re-emerging Pathogens, andchair of the university’s Institutional BiosafetyCommittee.


For almost thirty years, the Los AngelesPolice Department was stumped by thekillings of mostly poor black women by aserial killer known as the “Grim Sleeper.”Then police used DNA taken from one ofthe crime scenes and cross-referenced itwith the DNA of convicted criminals utiliz-ing a controversial new technique calledfamilial DNA searching. Familial DNAsearching operates off the principle thatwhen there is a partial (not exact) DNAdatabase match to a crime scene samplethere is a likelihood that the sample comesfrom someone related to the perpetrator.

They hit with a close match, a man whohad been convicted of a felony weaponscharge. The convicted man's father thencame under suspicion. DNA was liftedfrom a slice of pizza from the father. Whenthat was found to match evidence from thekillings, Lonnie David Franklin Jr., 57, wasarrested and charged with 10 counts ofmurder and one count of attempted mur-der.

Familial DNA searches target potential-ly millions of individuals that police knoware innocent and therefore have raised seri-ous civil rights and privacy concerns. Inparticular, the technique has raised con-cerns that DNA testing will fall dispropor-tionately on the shoulders of black andLatino populations and lead to even greater

racial disparities in the criminal justice sys-tem, which arrests and imprisons vastlymore African-American and Latino menthan other groups (who are therefore morelikely to appear in DNA databases).Considering that familial DNA searcheshave very low success rates—it had beentried unsuccessfully several times before inCalifornia—the practice appears dispro-portionately out of touch with democraticvalues.

The irony, here, is that Lonnie DavidFranklin Jr. is a convicted felon and shouldhave been in the database himself to beginwith and arrested as a result. The fact thathe wasn't is indicative of the already over-taxed and underfunded forensic systems.Without restraints—there are currently nostatutory limitations on familial DNAsearches—there are no guarantees that anysafeguards used in this particular case willbe replicated among the many policedepartments that will use this techniqueonce it is legitimized.

Singular cases make bad precedent. Asthe collection of DNA by law enforcementofficials has greatly expanded over the lastdecade, we need a much larger nationaldiscussion before sanctioning familialDNA searches for widespread use.


DNA Profiling Is Tested in CaliforniaIt worked to track one Los Angeles killer, but familial DNAsearching is still a highly flawed tool

BY CRG STAFF

Topic update

Conclusions

In most European countries, includingthe UK, there is a total lack of regulation ofDTC genetic tests, although a small numberof countries have imposed national restric-tions. Although the market for DTC tests iscurrently small, there is significant concernthat misleading tests will impact adverselyon patients and also divert healthcareresources from those in need to providingunnecessary follow-up tests and treatmentsto the 'worried well.'

In contrast to the USA, political enthu-siasm for transforming health services toenable the genetic 'prediction and preven-tion' of common diseases appears to be wan-ing within Europe (although it has not beenabandoned). This is due to a more realisticview of costs, privacy implications, and seri-ous doubts about whether the claimed healthbenefits would actually be delivered. Thus,economic realities and professional concernsare likely to restrict the adoption of geneticsusceptibility tests by publicly-fundedhealthcare services for the foreseeable future.

Whether DTC genetic tests will be ade-quately regulated by revising Europe's IVDDirective is currently uncertain. However,an extensive market in unregulated tests inEurope looks increasingly unlikely as healthservices seek evidence of the validity andusefulness of tests before their introduction.Responsible companies may find their besthope of survival lies in focusing on devel-oping and refining tests which actuallyimprove health outcomes for members of thepublic. This requires a very different busi-ness model from that being followed by thecurrent market-leaders. Instead of treatingwhole genome sequencing as inevitable, itimplies a focus on specific tests for use inhigh-risk families or prior to prescribing cer-tain drugs. To succeed in the European mar-ket, it seems likely that in the futurecompanies will need to demonstrate thattheir products provide benefits to health.In turn, this implies revisiting the underly-ing basis of long-standing but unsubstanti-ated claims about the genetic 'prediction andprevention' of common diseases in the gen-eral population.17

Helen Wallace is Director of GeneWatch UK,a research and public interest group thatinvestigates the environmental and socialimpacts of genetic science and technologies.

A UK PerspectiveContinued from page 13

The U.S. Food and Drug Administrationannounced on August 25 that it is consider-ing approval of a genetically engineered (GE)salmon for human consumption, which wouldmake it the first GE animal to enter the foodsupply. FDA only gave the public a few weeksto respond to this announcement and to ana-lyze their data even though they have had thisapplication on their desks for over ten years.This data revealed that these modified fishpose a variety of threats.

The GE salmon, created by a corporationcalled AquaBounty, is engineered to growtwice as quickly as its non-engineered coun-terparts—and that's cause for concern. If theGE salmon escapes from aquaculture farmswhere it is raised and enters the open ocean,it could contaminate natural populations withits genes and weaken salmon populations. Ofparticular concern is the survival of naturalAtlantic salmon, which are already listed asendangered. Indeed, research published in areport by the prestigious National Academyof Sciences indicates that a release of just 60genetically engineered salmon into the wildcould lead to the extinction of a natural pop-ulation of 60,000 salmon in less than 40 fishgenerations.

AquaBounty claims their fast-growing fishwould be contained and will not escape intolocal waterways. One not need look furtherthan the Asian carp in the Great Lakes toknow that even the best containment systemsfail. Natural disasters, wear-and-tear andhuman error can all lead to breaks inAquaBounty's containment systems andescaped genetically engineered salmon in ourwaterways.

The company also claims that their fishwill be sterilized, but even their own dataadmits that up to 5% of the eggs may remainfertile.1 AquaBounty claims to have ordersfor 15 million eggs.2 That means that rightoff the bat we may have up to 750 thousandfertile fish that can escape and wreak havocon the environment. Even more troubling isthe fact that AquaBounty will still need fertilemales and females to fertilize their geneticallyengineered eggs.

Human health is a pressing concern aswell. One consequence of government

approval of the genetically engi-neered salmon would likely be theuse of even more antibiotics in aqua-culture, increasing opportunities fordrug-resistant bacteria to develop.Farmed salmon are given moreantibiotics than any other livestockby weight3, and the GE salmon couldrequire even more antibiotics, sinceAquaBounty's fish would be less fit, makingthem even more susceptible to disease.

In addition, scientists have raised con-cerns about how physical properties of genet-ically engineered animals could make themunsafe to eat, but neither AquaBounty nor thefederal Food and Drug Administration havemade the GE salmon available to independ-ent experts for safety testing. It is irresponsi-ble for the FDA to say these fish are safe toeat without such testing.

AquaBounty's plan for raising these fishwas designed with the intent of avoiding U.S.environmental law. They plan on fertilizingthe eggs in Prince Edward Island in Canada,shipping them to Panama to be raised andprocessed, and then shipped back to the U.S.to be eaten. Despite open claims that they willexpand their operations to the U.S. and othercountries, the FDA is refusing to look at thecumulative harms their commercial operationwill have on the environment.

Fortunately, a final decision by the FDAhas not been made, and citizens are rising upto pressure the FDA to reject the geneticallyengineered salmon. 171,645 comments fromthe public were submitted to the FDAdemanding that this fish not be approved forhuman consumption. In addition, letterssigned by over 300 environmental and publichealth organizations, chefs, restaurants, andtribal communities were submitted telling theFDA to deny approval of the GE salmon.

On September 16, Friends of the Earth,Food and Water Watch, the Center for FoodSafety, and Ben and Jerry's organized ademonstration about the salmon in front ofthe White House. At the demonstration, CEOof Ben & Jerry's, Jostein Solheim, explainedwhy his company is against the GE salmon.Once the door is opened, he explained, theFDA is prepared to approve a number of

genetically engineered animals and Ben &Jerry's does not want a genetically engineereddairy cow to be next. In protest, theyannounced the symbolic renaming of theirfamous “Phish Food” ice cream to “Some-thing's Fishy” and passed out coupons for freeice cream to rally participants.

And on September 20, the public wasallowed to testify before an FDA committeeconsidering the GE salmon application.Friends of the Earth wrote comments to theFDA, which were signed by twenty otherorganizations in the U.S. and Canada, high-lighting the environmental threats posed byapproval of this genetically engineeredsalmon. We called on the FDA to conduct acomprehensive and independent environmen-tal impact review before any decisions onapproval are made.

The FDA committee recognized problemsin AquaBounty's plans and requested thatmore studies be conducted before this fish isapproved. The company's studies on healthsafety were poorly designed and their samplesizes, sometimes as low as twelve fish, wereway too small to guarantee safety.

Members of the committee also expressedconcern that not enough evidence exists toshow these fish will be safe if they escape intothe environment. The committee's only experton fisheries, Dr. Gary Thorgaard, called on theFDA to conduct an Environmental ImpactStatement—a comprehensive review of all theenvironmental risks—a sentiment echoed byother members of the Committee. If the FDAtakes this call to heart, it will allow time to fullyanalyze the environmental and health risksinstead of trying to rush the process throughas the FDA is currently attempting.

Eric Hoffman is Biotechnology Policy Campaigner at Friends of the Earth, an inter-national grassroots environmental network.


Fishy Business at the FDAGenetically engineered salmon carries a boatload ofproblems

BY ERIC HOFFMAN

Commentary

Robert Green et. al, p. 6

1.http://www.nytimes.com/2010/06/12/health/12genome.html?scp=1&sq=fda%20genetic%20test&st=cse

2.http://www.fda.gov/MedicalDevices/NewsEv-ents/WorkshopsConferences/ucm212830.htm

3. https://www.23andme.com/health/

Paul Billings, p. 10

1. Groopman, Jerome and Pamela Hartzband,“What's Your Underlying Condition?” NewYork Times, Nov. 26,2009.http://online.wsj.com/article/SB123914878625199185.html; “Why 'Quality' Care IsDangerous,” Wall Street Journal, April 8,2009.http://online.wsj.com/article/SB123914878625199185.html.

Helen Wallace, p. 12

1. Hogarth, S. (2010) Myths, misconceptionsand myopia: searching for clarity in thedebate about the regulation of consumergenetics. Public Health Genomics 13:322-326.

2. GeneWatch UK (2009) Is 'early health' goodhealth? GeneWatch UK Briefing. April 2009.http://www.genewatch.org/uploads/f03c6d66a9b354535738483c1c3d49e4/Data_mining_brief_fin_3.doc

3. Fleming, I (2008) Rival genetic tests leavebuyers confused. The Sunday Times. 7th Sep-tember 2008.http://www.timesonline.co.uk/tol/news/sci-ence/article4692891.ece

4. Further information is available on:http://www.genewatch.org/sub-558225

5. European Technology Assessment Group(2008) Direct to Consumer genetic testing.November 2008.http://www.itas.fzk.de/eng/etag/docu-ment/2008/heua08a.pdf

6. Henderson, H. (2010) Cashing in on yourgenes. The Times, 7th January 2010.

7. www.eurogentest.org 8. Kristofferssson, U. Schmidtke, J., Cassiman,

J.-J. (Eds) Quality issues in clinical geneticservices. Springer. 2010.

9. PHG Foundation (2010) Genomic Medicine.An independent response to the House ofLords Science and Technology CommitteeReport. May 2010. www.phgfoundation.org

10. How seriously should we take risk predic-tions for multifactorial illnesses? Available on:https://www.eshg.org/fileadmin/www.eshg.org/documents/received/2010MultifactorialD-

iseases.pdf 11. Wallace HM (2006) A model of gene-gene

and gene-environment interactions and itsimplications for targeting environmentalinterventions by genotype. Theoretical Biol-ogy and Medical Modelling, 3 (35),doi:10.1186/1742-4682-3-35.

12. Prasad, K. (2009) Role of regulatory agenciesin translating pharmacogenetics to the clinics.Clin Cases Miner Bone Metab. 6(1): 29-34.

13. Available on: http://ec.europa.eu/enter-prise/newsroom/cf/itemlongdetail.cfm?item_id=4404&tpa_id=164&lang=en

14. Additional Protocol to the Convention onHuman Rights and Biomedicine concerningGenetic Testing for Health Purposes CETSNo.: 203http://conventions.coe.int/Treaty/Com-mun/QueVoulezVous.asp?NT=203&CM=8&DF=17/09/2009&CL=ENG

15. Wallace HM (2008) Most gene test sales aremisleading. Nature Biotechnology, 26(11),1221.

16. European Society of Human Genetics (2010)Statement of the ESHG on direct-to-con-sumer genetic testing for health-related pur-poses. European Journal of Human Genetics1-3.https://www.eshg.org/fileadmin/www.eshg.org/documents/PPPC/2010-ejhg2010129a.pdf

17. GeneWatch UK (2010) History of thehuman genome. GeneWatch UK briefing.June 2010.http://www.genewatch.org/uploads/f03c6d66a9b354535738483c1c3d49e4/HGPhistory_2.pdf

Jeremy Gruber, p. 18

1.http://www.newscientist.com/blogs/short-sharpscience/2010/06/personal-genome-cus-tomers-sent-1.html

2. Bradley Malin and Latanya Sweeney, Deter-mining the Identifiability of DNA DatabaseEntries, 2001 Journal of the American Med-ical Informatics Association 423.

3. 23andme Privacy Statement (accessed on7/12/10 athttps://www.23andme.com/about/privacy/)

4. See, for example, United States, FederalTrade Commission, At-home Genetic Tests:A Healthy Dose of Skepticism may be theBest Prescription (2006), online: FederalTrade Commission(http://www.ftc.gov/bcp/edu/pubs/con-sumer/health/hea02.shtm)

Andrew D. Thibedeau, p. 20

1. Plato, The Republic, ed. Jeffrey Henderson,

trans. Paul Shorey (Cambridge: Harvard Uni-versity Press, 1935), 186-188 (1935); JamesAdam, The Republic of Plato Edited withCritical Notes, Commentary and Appendices(Cambridge: The University Press, 1921),130-131 n. 12.

2. Elizabeth A. Martin et al. eds., Concise Med-ical Dictionary, 8th ed. (New York: OxfordUniversity Press, 2010), 753.

3. Kevin Davies, The $1,000 Genome: The Rev-olution in DNA Sequencing and the New Eraof Personalized Medicine (New York: FreePress 2010), 87. The Rothberg Institute forChildhood Diseases, at www.childhooddis-eases.org (accessed August 27, 2010).

4. Davies, 87.5. Michael Reis, “A Grand Vision Becomes Real-

ity,” Stone World 22, no. 1 (January 2005):146-47.

6. Davies, 84.7. Davies, 77.8. Barbara Katz Rothman, Genetic Maps and

Human Imaginations: The Limits of Sciencein Understanding Who We Are (New York:W.W. Norton & Company, Inc. 1998), 13.

9. Quoted in Davies, 47.10. Quoted in Davies, 58.11. Davies, 69.12. Davies, 68.13. Quoted in Davies, 58.14. Government Accountability Office, Direct-

to-Consumer Genetic Tests: Misleading TestsResults are Further Complicated by DeceptiveMarketing and Other Questionable Practices,GAO-10-847T (July 2010), 2 (“2010 GAOReport”)

15. Dorothy Nelkin and M. Susan Lindee, TheDNA Mystique: The Gene as a Cultural Icon(Ann Arbor: University of Michigan Press,2004): 2.

16. Søren Holm, “There is Nothing Specialabout Genetic Information,” in Genetic Infor-mation: Acquisition, Access, and Control, ed.Alison K. Thompson and Ruth F. Chadwick(New York: Plenum Publishers, 1999), 98.

17. Nelkin Lindee, The DNA Mystique,165.18. Davies, 8.19. 2010 GAO Report, 2.20. Davies, 148.21. Quoted in Davies, 56-57.22. Davies, 72.23. Davies, 180.24. 2010 GAO Report, 15.25. United Kingdom Directorate General for

Internal Policies, Policy Department A: Eco-nomic and Scientific Policy, Direct to Con-sumer Genetic Testing,IP/A/STOA/FWC/2005-28/SC32 & 39 (Nov.2008), 31 (“UK Study”).

26. Bryn Williams-Jones and Vural Ozdemir,“Challenges for Corporate Ethics in Market-


Endnotes

ing Genetic Tests,” Journal of Business Ethics77, no. 1 (2008): 36 (emphasis in original).

27. 2010 GAO Report, 4.28. Quoted in Davies, 163 (emphasis in origi-

nal).29. Direct_to_Consumer Genetic Testing and

the Consequences to the Public Health: Hear-ing Before the Subcom. on Oversight andInvestigations of the H. Comm. on Energyand Commerce, 111th Cong. 77 (Jul. 22,2010) (testimony of Dr. James Evans, Editor-in-Chief, Genetics in Medicine, Bryson Pro-fessor of Genetics and Medicine, Universityof North Carolina at Chapel Hill).

30. C. M. Condit, “Public Understandings ofGenetics and Health,” Clinical Genetics 77,no. 1 (2010): 2.

31. Davies, 72.32. UK Study, 101.

Nancy Connell, p. 22

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Casadevall A, Imperiale MJ. 2010. Destructionof microbial collections in response to selectagent and toxin list regulations. BiosecurBioterror. 8(2):151-4.

Connell, N. and B. McCluskey. 2010. BringingBiosecurity-related Concepts into the Cur-riculum: A US View. In Education and Ethicsin the Life Sciences: Strengthening the Prohi-bition of Biological Weapons. (B. Rappert,ed.). The Australian National UniversityPress. Canberra ACT 0200, Australia.

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GeneWatch Anniversary Archive: 1983-2008

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

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