While it will likely be a year or more before a final regulation takes effect, and there will almost certainly be amendments along the way, American companies – including those involved in the field of personalized medicine, where personal data is paramount by definition – should start paying attention now, since they may have to change the way that they do business in Europe.

We will provide a more detailed analysis of the Draft Regulation at a later date. In the meantime, here are some of the key issues we are examining:

• It is significant that the Commission is acting by Regulation rather than Directive (as was the case with the current privacy law, enacted by Directive in 1995). A regulation is top-down, imposed uniformly throughout the EU, whereas a directive is adopted country-by-country, which gives individual nations the chance to make adjustments.
• The EU is taking a very aggressive approach to jurisdiction, or its authority to regulate—and impose penalties on—U.S. and other foreign companies that do business in Europe. The Draft Regulation would cover all data processing activities (very broadly defined) by non-EU companies that involve offering goods or services to EU data subjects or monitoring their behavior.
• Data subjects (also broadly defined) will have significantly more rights than under current EU law. For example, the company will have the burden of proving that every subject has given consent for the processing of their data for specified purposes. Consent is defined as “any freely given specific, informed and explicit [emphasis added] indication of will,” and can be withdrawn at any time. The subject will also have a controversial “right to be forgotten and to erasure.” This means that when the subject withdraws consent or “the data are no longer necessary” for the purposes for which they were collected, the company must render the data inaccessible, including on the Internet.
• Along with data pertaining to race or ethnic origin, political opinions, religion or beliefs and trade-union membership, the Draft Regulation identifies “genetic data” as category of personal data designated for special protection. (The Draft Regulation defines “genetic data” broadly to include “all data, of whatever type, concerning the characteristics of an individual that are inherited or acquired during early prenatal development,” thus presumptively sweeping in all genetic information as well as family medical histories and other related health information.) Special protections include impact assessment and prior authorization of data processing operations, and activities lacking sufficient identification or mitigation of risks to individuals may be prohibited.

These are just a few of the more important features of the 96-page, 91-Article Regulation.

Elsewhere, the Draft Regulation would create other new rights and responsibilities and reaffirm and/or strengthen many provisions of existing law, including the current restrictions on transferring data outside of the EU. Ironically, the Draft Regulation notes that the “practical challenges to enforcing data protection legislation” across boundaries and the “risk of different levels of protection…creat[ing] restrictions on cross-border flows of personal data” between jurisdictions. While the Draft Regulation may ease some of these concerns within the EU, global companies seeking to move personal data in and out of the EU face a different calculus.

The draft must now be reviewed by several Directorates of the EU Commission before being submitted for review and approval by the Parliament and Council. But while full implementation will take some time—more than a year in most estimates—the proposed changes are so dramatic and far-reaching that U.S. companies doing business in Europe will require at least that much lead time to plan their compliance.

Patent Reform Legislation Passes House. Several months after the U.S. Senate passed patent reform legislation that would make sweeping changes to America’ patent system, including a switch from a first-to-invent to a first-to-file system for awarding patents, the U.S. House of Representatives finally followed suit yesterday, passing a similar piece of legislation by a vote of 304-117. The version passed by the House, while similar to that passed by the Senate, contained a number of last-minute amendments (pdf).

One change of particular relevance to the personalized medicine community was the removal of a proposed safe harbor for second opinion genetic diagnostic testing, which was replaced by a requirement that the U.S. Patent and Trademark Office (USPTO) investigate the relationship between genetic diagnostic tests, gene patents and exclusive licenses. The USPTO would be given nine months to complete its investigation and to return to Congress recommendations for ensuring the availability of second opinion genetic diagnostic testing. (The USPTO study on genetic diagnostic testing was not included in the bill passed by the Senate in March.)

With both the House and the Senate having now passed patent reform legislation, the next step appears to be a House-Senate conference to resolve inconsistent provisions in the two bills, although according to The Hill it is unclear how soon such a conference will take place.

UK Government Pulls Plug on Human Provenance Project. Nearly two years after the Human Provenance Project was first unveiled (to substantial scientific criticism), the government agency responsible for the project, the UK Border Agency, has finally pulled the plug. The project would have used DNA and isotope analysis of tissues from asylum seekers in an attempt to evaluate their nationality and render immigration decisions. After a wave of criticism following the program′s announcement, and after spending more than $300,000 on screening, the UK Border Agency has scrapped the program in its entirety.

As we wrote back in 2009, the poorly conceived project threatened to disrupt what has been—in both the UK and in the United States—a slow and delicate process to craft legislation, regulation and policies that promote genomic science and the use of personalized genomic data while addressing concerns over the potential misuse of those data. As we wrote then, “with so much genomic science and policy yet to be written, even minor developments produce outsized effects, which makes the potential consequences of the Border Agency’s project so worrisome.”

Thankfully, the UK Border Agency quickly paused the project following initial concerns and, nearly two years later, it appears that no lasting damage has been done. Still, the Human Provenance Project should serve as a reminder to governments worldwide of the need to carefully and publicly vet state-directed personal genomics programs prior to their implementation.

Roundup of tweets from the intersection of genomics, personalized medicine and the law:

• Combined w/ this week’s GenomeQuest announcement (http://bit.ly/kCp0j2) & it’s clear clinical, commercial WGS is here. Now.
• Omicia releases genome annotation software (incl. for clinical/commercial applications) http://bit.ly/l1XpJ6 HT @neandrothal @EricTopol
• FDA report on challenge of monitoring imported food, drugs (http://1.usa.gov/mmWpgd) hints at > difficulty monitoring info-based Dx/devices.
• Study: FDA device clearance times rose 37% since 2006: http://bit.ly/jRxrrV Other news: FDA device studies criticized: http://bit.ly/jGVBH0
• FDA accused of focusing too much on safety (http://bo.st/mCCad9) & of doing too little: http://bit.ly/il4maZ Damned if you do…
• Finally responding to this @genomesunzipped thread. Agree w/ @dkgppc re: need for more data: http://bit.ly/mERhg8 Any ideas how to collect?
• The beat(down) goes on: FDA accused of being a “wet blanket” & “crushing innovation” by MA senator: http://bo.st/kTWrmk
• GLR Post: Prometheus Returns to the Supreme Court, Medical Method Patent Speculation Intensifies: http://bit.ly/kqnDWP
• MT @danielg280: Doing a Webinar 6/21 on legal issues re healthcare & social media w/ @healthblawg http://bit.ly/l2SFvY
• High-level explanation from @wilbanks why for patents, unlike copyrights, transparency is priority #1: http://bit.ly/mRqJAv
• Great idea. MT @RyanMFierce: NC wants to help cash-strapped biotechs w/ $100M in loans http://bit.ly/mau3Gj cc @GlenCaplan
• Still, for efforts like the Human Provenance Project, it can be difficult to unring the bell: http://bit.ly/kRciNK
• $300K too late, but right decision. RT @NatureNews: UK immigration cancels DNA screening programme http://goo.gl/fb/YwQ49
• “The 3 letter word for-the gene FOR something-is the most dangerous word in genetics.” http://bbc.in/mKTY1P HT @eurogene
• MT @matthewherper @ivanoransky @charlesornstein: Despite FDA Criticism, Cancer Drugs Reach Pts Sooner In US Than Europe http://bit.ly/msJTuL
• RT @SampleGW: New Consortium Aims to Streamline Accreditation, Proficiency Testing: http://bit.ly/lBJBLD
• Let’s just hope we do better than MSWord. RT @FierceHealth: Patient rights, safety at heart of #EHR track changes debate http://htl.li/5jkIR
• RT @SampleGW: Medicare to Cover Pathwork Diagnostics’ Tissue of Origin IVD Nationwide: http://bit.ly/kIIOmW
• Well said, @23andMe: “research is a two-way process, where participants are valued as partners in sci. discovery.” http://bit.ly/lgWLrW
• GLR Post: Update: Proposed Second Opinion Safe Harbor for Genetic Diagnostic Testing Withdrawn: http://bit.ly/kOX7qx
• ACLU-led coalition opposes proposed safe harbor for 2nd opinion Dx testing, citing “unintended harms”: http://bit.ly/lJKrqL
• Not only co. to shift focus, at least for moment. MT @RyanMFierce 95% of @Knome revenue from R&D, 5% from customers. http://bit.ly/lFwPow
• House debate on patent reform bill delayed until (at least) next week: http://bit.ly/jtbjY1
• RT @dgmacarthur: New community forum for @CompleteGenomic users: http://bit.ly/kHoys3 Just signed up – interested to see how active it gets.
• GLR Post: DTC Genetic Testing and the FDA: is there an end in sight to the regulatory uncertainty? http://bit.ly/koxrjn
• GLR Post: House Introduces Patent Reform Proposal to Permit 2nd Opinions in Genetic Diagnostic Testing http://bit.ly/j5DeWl
• AdvaMed’s “competitiveness policy” urges creation of “office of medical innovation policy” w/in White House: http://bit.ly/iqXXv9 Good idea.
• “Med-tech CEOs storm Capitol Hill”: http://bit.ly/iBBJNz by @MassDevice Seem unlikely to hear Shuren’s plea for mercy
• Meanwhile, @dgmacarthur @lukejostins & I wonder when DTC regulatory uncertainty might end: http://bit.ly/lxLKda
• CDRH Director Shuren says criticism is affecting hiring, slowing agency: http://bit.ly/maZddr HT @dgmacarthur
• Ion Torrent ($LIFE) expects 400bp reads by year end, $1K genome beginning of ’13: http://bit.ly/kf3tVZ @InSequence
• Update on Noblegen’s “optipore” sequencing tech; targeting clinical seq tests, ’14 debut: http://bit.ly/m55KhH @InSequence
• RT @BVBigelow: BioNanomatrix Moves HQ and nano-scale molecular analysis tech to San Diego’s diagnostics cluster. http://bit.ly/iA2JHx
• RT @RyanMFierce: Broad Institute’s planned expansion roughly the size of two Wal-Mart stores. Wow. http://bit.ly/lCBlsf by @BBJNewsroom
• RT @DailyNewsGW: NIH Awards $200M for New CTSA Sites: http://bit.ly/lO3pdA
• Twin’s rare disease diagnosed, cured. Another “win” for whole-genome seq: http://bit.ly/kuxupr by @Erika_Check HT @drgitlin
• RT @PGxReporter: MDx/PGx Highlights from ASCO 2011: http://bit.ly/mJSwL1
• GLR Post: House Introduces Patent Reform Proposal to Permit 2nd Opinions in Genetic Diagnostic Testing http://bit.ly/j5DeWl
• RT @JohnCFierce: Cancer collaborations are all the rage – but you already knew that. http://bloom.bg/jyuqHA by @robertlangreth
• The “strangest biotech of all” ($UTHR) by @matthewherper, incl a look at its comic book annual report (really): http://onforb.es/lNfZ9w
• RT @dgmacarthur: MT @westr Illumina launching 5M-variant whole-genome genotyping array – the Omni5 – focus on rare variants: bit.ly/ilnaL2
• RT @ldtimmerman: Getting ready for debate on open source bio w/ @sagebio founder Stephen Friend, MIT’s Phil Sharp http://bit.ly/jshQ77
• +1. RT @neandrothal: Chrome extension soon? MT @dgmacarthur: update to handy @SNPTips FireFox plugin for @23andMe data: http://bit.ly/iCDxuP
• The perfect Father’s Day gift? It’s probably not a paternity test: http://bit.ly/iG1QJ9 by @SampleGW
• Here’s more from @23andMe on the breakdown of their database: http://bit.ly/lfldx2 Note that not entire 100K have opted in for research.
• DTC company @23andMe continues to reposition itself, emphasizing reasearch database (now 100K): http://bit.ly/mNnJPF
• Following @phylogenomics for tweets from #synbio5, including current coverage of @geochurch’s talk.
• RT @dgmacarthur: Serious congrats to @markgfh, who won both the European Best Cancer Reporter award & Royal Statistical Society prize today!
• Beginning w/ improved understanding of heterogeneity. RT @FierceBiotech @MaverickNY: changing cancer research paradigm. http://bit.ly/mtJc4y
• RT @JohnCFierce: My take on E&Y’s annual biotech report: It’s tough out there, says Giovannetti http://bit.ly/mm2pN3
• MT @Knome: Today we announce the launch of kGAP 2.0, the 2nd ver. of our #genome interpretation engine http://ow.ly/5hfR7
• RT @genomesunzipped: New Interpretome website provides many handy tools for analysing your @23andMe data: http://bit.ly/lHd2Yw
• RT @LifeSciVC: Welcome my Atlas partner @JFFormela to the Twittersphere. He will undoubtedly have blazing content & sharp wit to add
• RT @westr: 23andMe’s customer breakdown by ethnicity, via @CeCeLMoore http://tinyurl.com/3h5zcv8
• RT @GenCounsNews: Update on advanced degree task force for genetic counselors, including a webinar later this summer http://bit.ly/ilBTHD
• & SEC. Still, can be done. RT @elainewestwick: suspect IP/secrecy concerns a challenge re: Twitter/biotech http://bit.ly/kTWx63 @ldtimmerman
• Brief recap from last week’s MDMA meeting, including familiar FDA criticism from Senator Hatch: http://bit.ly/jwEzdv by @FierceMedDev
• Commons Principles from @Sagebio posted: http://bit.ly/jHEAp2 Ambitious, essential & endorsement-worthy. Add your voice.
• Congrats to @KeonaHealth, Sarda Tech (my dad’s new venture) & others on NC IDEA innovation grants: http://bit.ly/mKsgJd
• Exciting news. RT @neandrothal @NextBio: blog is back w/ a screenshot of upcoming new public site! http://wp.me/pmGXL-e6
• DTC genetic testing company @Lumigenix: “our response to a recent letter from the FDA”: http://bit.ly/lzfL6o
• “I joined GenomeQuest b/c they offer technology to make whole genome dx avail. to patients today-not 10 yrs from now.” http://bit.ly/jR2gVx
• Why Twitter matters for biotech, by @ldtimmerman: http://bit.ly/kTWx63 No surprise, lawyers even slower to adopt Twitter.
• Post by @eurogene on breast feeding, IQ, genetic testing & DTC: http://bit.ly/lGjrDp Comments from @23andMe or @ExistenceG?
• $0.02 from @matthewherper on @patientslikeme tool to match patients to trials using Clinicaltrials.gov: http://onforb.es/m3VmVw
• RT @dgmacarthur: Congrats to @genomesunzipped colleague Don Conrad on his new Nat Genet paper on human mutation rates: http://bit.ly/mhyXgu
• RT @drjonboyg: Raised in this wk’s In Our Time: was germ theory or cracking genetic code biggest leap in human health? http://bit.ly/mkY7p8
• Will need more than 31 senators. RT @NatureNews: NIH finds a few new friends in budget chill http://goo.gl/fb/mfM8O
• RT @westr: “Consumer Genetics Conference Wrap-up – Most Interesting Moments?: http://bit.ly/m5BStq #CGC2011″ -via @wimufi
• MT @mary_carmichael: @dgmacarthur Screenshots don’t do it justice. Key is in use: easy to navigate, cross-ref diff types of content.
• Privacy vs. efficacy driving debate over opt-in or opt-out approach to state EHR systems: http://bit.ly/fD5mF8
• GLR Post: News Roundup: Perception Gaps and Progress in Personalized Medicine: http://bit.ly/kWv9nn
• Company for Shuren? “Health Canada upbraided for inspections of medical devices.” http://bit.ly/l4Kw9e
• RT @BiotechPatent: FDA takes ‘first step’ toward greater regulatory certainty around nanotechnology http://1.usa.gov/jipVTX
• Drugmakers’ Commitment to Personalized Rx Growing Despite Barriers, PhRMA CEO Says: http://bit.ly/jBcQ73 by @PGxReporter
• RT @dgmacarthur: Screenshots of the $ILMN iPad personal genome browser (HT @BioITEditor): http://bit.ly/k06xA9 Surprisingly amateurish.
• RT @genome_gov: Cool 7/18 meeting: Using crowdsourcing for scientific innovation @ NIH’s Natcher auditorium (also webcast) http://qoo.ly/4z7
• FDA ruling on $OREX’s Contravene obesity drug risks driving scarce R&D resources from important field, says @LifeSciVC: http://bit.ly/la5nsi
• RT @cwhogg: Wireless dominates patents for heart, glucose monitors http://tinyurl.com/3ur7jmz
• RT @scotthensley: Curious to see how it’ll work. RT @phrma: Forthcoming @US_FDA Facebook page that will answer ppl’s questions about drugs
• #ASCO11 wrap-up from @ldtimmerman for those (read: all of us) who had difficulty following all of the news: http://bit.ly/kDFaA2

UK Insurers Continue Moratorium on Predictive Genetic Tests. In 2008 the United States passed the Genetic Information Nondiscrimination Act (GINA). Title I of GINA prohibits health insurers from using genetic information to deny coverage or to set premiums or payment rates. Title II of GINA addresses the use and misuse of genetic information by employers. In the United Kingdom, which provides universal health coverage through the government-funded National Health Service (NHS), discussion of genetic nondiscrimination has largely focused on the employment context (see, e.g., the 2009 report on Genomic Medicine from the House of Lords). To date, however, the United Kingdom has not enacted a formal prohibition on the use of genetic information by either employers or insurers.

Although the U.K. lacks a formal counterpart to GINA, in 2001 the Association of British Insurers (ABI) and the government’s Department of Health did establish a voluntary moratorium on the use of predictive genetic testing by insurers. According to the ABI:

The moratorium means the results of a predictive genetic test will not affect a consumer’s ability to take out any type of insurance other than life insurance over £500,000. Above this amount, insurers will not use adverse predictive genetic test results unless the test has been specifically approved by the Government. Only around 3% of all policies sold are above these limits. The only test that is approved is for Huntington’s Disease.

The moratorium was initially scheduled to expire in 2011. It was extended until 2014 in 2008 and, this past week, it was extended again, to 2017. The moratorium is scheduled to be revisited again in 2014.

Myriad Oral Argument. As regular GLR readers already know, the latest development in the Myriad gene patent litigation occurred on Monday. The Federal Circuit heard oral argument in the case, which will likely be the last public step before the three judge panel issues its opinion in several months. We’ve already discussed here at the GLR what we learned from the Myriad oral argument, but there has been excellent coverage of the case elsewhere as well. At the Pharmacogenomics Reporter, Turna Ray explored the somewhat confusing position Myriad took at oral argument with respect to the relationship between the company’s BRCA patents and whole-genome sequencing. In addition, the lead up to the oral argument also produced some interesting analyses, including at The Atlantic, where Andrew Cohen provided a play-by-play account of the events to date, and at Nature.com, where Shobita Parthasarathy focuses on how Myriad, regardless of its outcome, has produced “a more democratically engaged patent system.”

One other patent-related note: for those who are wondering what a government shutdown later today might mean for the US Patent Office, Patently-O has the answer. [Update: Nature also has an excellent high-level overview of how a shutdown will affect various government agencies, including the NIH and the FDA.]

Breast Cancer’s Complexity. Finally, a recent study from researchers at Washington University in St. Louis serves as a reminder that our knowledge of breast cancer, despite the ongoing litigation over the BRCA1 and BRCA2 genes, is still woefully incomplete. Scientists led by Matthew Ellis have sequenced the whole genomes of fifty patients’ breast cancer tumors along with matching DNA from the same patients’ healthy cells. They presented these results at the Annual Meeting of American Association for Cancer Research on April 2nd and revealed that most of the 1700 genetic mutations discovered were unique to individual patients’ tumors and only three occurred in 10% or more of the patients.

The sample was from patients in clinical trials of estrogen-lowering drugs known as aromatase inhibitors. Patients who are not responsive to such drugs have lower survival rates, but scientists do not know what causes these differences. One such association was for the breast cancer suppressor gene MAP3K1, which produces a protein that accelerates programmed cell death. MAP3K1 mutations were associated with the aromatase inhibitor-sensitive–more favorable–type of disease and were present in about 10% of the tumors. This result may be beneficial for pharmacogenomics research aimed at targeting particular types of breast cancers – similar to the research that led to the Genentech drug, Herceptin.

The next step will be to repeat the experiment with a much larger sample size (at 1,000 tumors), an indication of just how far we have to go when it comes to truly understanding how diverse cancers operate in equally diverse individuals.  Additional coverage is available from GenomeWeb and The Wall Street Journal.

Roundup of tweets from the intersection of genomics, personalized medicine and the law:

• RT @GenomeWeb_News: Macquarie Begins Coverage of five clinical labs, incl Genomic Health, Myriad Genetics: http://bit.ly/g1JS7n
• Using BRACAnalysis as companion Dx RT @GenomeWeb_News: Myriad Partners with BioMarin on PARP Inhibitor: http://bit.ly/fMVasv
• More on Myriad & WGS by @pgx_reporter (http://bit.ly/eleiCG) but, really, no clear guidance in oral argument & doubtful in opinion either.
• RT @daphnezohar: Taking a closer look at the significance of statistical significance http://on.wsj.com/gDOkTF
• MT @CompleteGenomic: We’ve added 29 human genome sequences to public repository. 69 avail now <http://bitly.com/gyvaVo>
• RT @GENbio: Translational Research Is the NCATS’ Meow for Growing NIH’s R&D Role http://bit.ly/goYKfo
• Genetic data & no use for it *right this second*? Throw it away, obviously. @MishaAngrist w/ a too-rare blogging foray: http://bit.ly/fA6rNY
• For the full HGC report & recommendations – which are perfectly sensible – on carrier screening see here: http://bit.ly/hLkLeI
• Carrier screening a “modern version of eugenics” & “immensely dangerous”: http://bbc.in/f77iR1 Big, scary words for short, cursory BBC story
• MT @dgmacarthur: My carrier test op-ed (http://thetim.es/guUD0n) & excellent piece by @markgfh (http://thetim.es/guUD0n) – both £, sadly!
• RT @FierceBiotech: Gene-patent courtroom drama plays out in Washington. http://bit.ly/dSxcja
• GLR Post: What We Learned From the Myriad Oral Argument: http://bit.ly/gRUaiB (Short version: wait until June)
• RT @NatureNews: Patent dispute threatens US Alzheimer’s research http://goo.gl/fb/MH9vN
• RT @dgmacarthur: Computation guru Stephen Wolfram had his genome sequenced by $ILMN, found little of interest: http://bit.ly/ewNNhs
• RT @JohnCFierce: WSJ adds its own bleak assessment of biotech IPO market. Weak demand gives pharma an edge. http://on.wsj.com/fECZOe
• RT @bioitworld: UK insurers renew moratorium on using predictive genetic tests (except Huntington’s) http://bit.ly/eX4akZ
• Not first time in ’11 contingency plan developed. RT @ScienceInsider: NIH’s ‘Secret Plans’ for a Government Shutdown: http://bit.ly/i9TG71
• RT @ldtimmerman: Welcome to New York post from @xconomy NY editor Arlene Weintraub @awjourn http://bit.ly/g1ti4A
• HHMI announces $60M grant competition challenging universities to “think creatively” about science education: http://bit.ly/f02DHm
• RT @GenomeWeb_News: Oppenheimer Revises Revenue Estimates for Life Technologies: http://bit.ly/f1YPRj
• RT @GenomeWeb_News: Goldman Sachs Adjusts Illumina EPS, Revenue Estimates: http://bit.ly/gxvT20
• Welcome to NYC! RT @Xconomy: Xconomy opens in New York City, the sixth hub in our expanding network: http://bit.ly/hhP1Oz
• Audio from Myriad gene patent oral argument is now available online: http://bit.ly/dMLSYK
• RT @InSequence: Cancer Genome Atlas Aims to Sequence 3,000 Tumor/Normal Pairs by Year-End: http://bit.ly/h3sIgH
• RT: @ipwatchdog WH to hold Startup America Roundtable in St. Paul on April 6th http://bit.ly/h5xlcs includes reducing barriers roundtable
• RT @GenomeWeb_News: Ion Torrent Certifies Ambry Genetics: http://bit.ly/geT9vf
• Hard question to which there is no current answer RT @23science: will FDA send VU a letter too? http://bit.ly/hWijEt
• Vanderbilt’s ambitious attempt to integrate EHRs & genomic data/research for cancers: http://bit.ly/hWijEt Much more like this needed.
• RT @23andMe: DTC Genetic Tests and the Future of Regulation: Make Your Voices Heard: http://bit.ly/g8ECDz #FDADTC
• GLR (Re)Post: A Spectator’s Guide to Today’s Oral Argument in Myriad Gene Patent Litigation: http://bit.ly/eqbjz9
• Next step: repeat with 1,000 more. RT @NatureNews: Fifty genome sequences reveal breast cancer’s complexity http://goo.gl/fb/f5Hxk
• RT @GenCounsNews: Collaboration among multiple Alzheimer’s research groups leads to id of new genes http://nyti.ms/exEFSC
• Update to the @PGorg website includes publicly available copies of revised consent forms: http://bit.ly/hC2YH1
• RT @mikesgene: Post-Doctoral Position at Center for Genetic Research Ethics and Law http://bit.ly/dRlNXq #genome #GE3LS
• (And congrats to @shwu on the author credit for the 24th chromosome. Can a nobel be far behind for such a momentous discovery?)
• Heh. RT @23andMe: Blog Post- 23andMe Discovers 24th Chromosome, Changes Name to 24andMe: http://bit.ly/eSmZSG
• Isn’t seeming “pointless but cool” a great result for a new ad? re: Ion Torrent’s tilt-shift video ad: http://bit.ly/hVOSpP HT @dgmacarthur
• Friday Links @genomesunzipped: @23andMe confirms identical twinnery; tell FDA what you think about DTC genetics: http://bit.ly/eReQPD
• RT @shwu: All #FDADTC presentations and comments (submitted by Mar 1 deadline) now available at http://1.usa.gov/i24b7F
• RT @InSequence: Grants Drive 47 Percent Growth in Helicos 2010 Revenues, but Add’l Funds Needed to Stay Afloat: http://bit.ly/eFhMTj
• GLR Post: Weekly Roundup: Science Funding, DTC and Medical Device Caucusing http://bit.ly/ih9Fod
• GLR Post: A Spectator’s Guide to Monday’s Oral Argument in Myriad Gene Patent Litigation: http://bit.ly/eqbjz9
• Mayo petitions Supreme Court for cert (again): http://bit.ly/gizf6T After most recent ruling (http://bit.ly/gvBOVx) a grant seems unlikely.
• House version of Patent Reform Act closely tracks Senate’s, with a few key exceptions: http://bit.ly/eQNHN0 by @patentlyo

Robert Cook-Deegan contributed to this commentary. Dr. Cook-Deegan is

The past few months have brought a number of significant research and commercial developments in the BRCA diagnostic testing market, particularly in Europe. These developments have been met by enigmatic comments from the management of Myriad Genetics, the sole provider of commercial BRCA diagnostic testing in the United States and a defendant in ongoing and closely-scrutinized gene patent litigation. What can these recent developments tell us about Myriad’s future plans in both Europe and the U.S.?

The Next Generation of BRCA Testing. Myriad’s current BRCA diagnostic test, BRACAnalysis (pdf), uses a combination of two traditional technologies—Sanger sequencing and PCR—to identify mutations associated with a significant risk of breast cancer and/or ovarian cancer in the BRCA1 and BRAC2 genes. Although Myriad has dabbled with next-generation sequencing technologies, Myriad has yet to announce any concrete plans to apply any of the increasingly numerous and powerful next-generation sequencing technologies to its BRACAnalysis testing.

Others, however, are moving rapidly in exactly this direction.

In April 2010, Mary-Claire King and her colleagues at the University of Washington published a paper in PNAS (pdf) that described the massively parallel sequencing of 21 genes, including BRCA1 and BRCA2, but also 19 other genes that, when mutated, confer an increased risk of breast and/or ovarian cancer. They offered their research as “proof of principle for the application of solution capture and next-generation sequencing to mutation detection for patients at high risk of breast cancer.” A next-generation sequencing approach to breast cancer testing, they determined, could successfully detect far more deleterious mutations in far more relevant genes than the Myriad test detects, and could do so at a fraction of the cost of the commercial BRCA testing performed by Myriad in the United States.

Next, in October 2010, Stephen Salzberg and Mihaela Pertea published what they described as a “Do-it-yourself” approach to BRCA diagnostic testing. The Salzberg Screen, as it is known, analyzes previously obtained genomic sequence data (e.g., from whole-exome or full-genome sequence data, which is commercially available) for BRCA mutations by querying publicly available resources. Salzberg and Pertea freely acknowledged that a primary motivation in supplying the Salzberg Screen was “to empower any individual…to test for [BRCA] mutations and circumvent [Myriad’s] gene patents.” In assessing the Salzberg Screen and its impact on Myriad we noted that Salzberg and Pertea were taking a “calculated gamble” in this regard. The test separates the crucial steps of sequencing and interpretation, arguably avoiding direct infringement claims for many of Myriad’s broadest patents, although arguments based on inducement of infringement might remain viable. We wrote then that Salzberg and Pertea were likely gambling that Myriad simply lacked the stomach to initiate any additional BRCA-based litigation and, at least so far, their gamble appears to have paid off.

Importantly, the integration of next-generation sequencing data in BRCA testing is not just a subject for medical journals. It is also beginning to find its way into clinical and commercial applications.

This past October, two European research hospitals—Ghent University Hospital in Belgium and the University of Leeds Institute of Molecular medicine in the United Kingdom—announced plans to use next-generation sequencing technology to perform diagnostic sequencing for BCRA1, BRCA2 and other genes. And just this past week, a British company called NewGene announced plans to sequence the entire coding region of BRCA1 and BRCA2 genes for UK patients with a family history of breast cancer.

Both NewGene and the research laboratories intend to utilize so-called next-generation sequencing technology in performing BRCA diagnostic testing. Both New Gene and Ghent University Hospital employ the Roche 454 GS-FLX pyrosequencing platform, while Leeds is proceeding with Illumina’s Genome Analyzer.

Finally, last month, at the Advances in Genome Biology and Technology (AGBT) meeting, GenomeQuest announced a “clinical diagnostics reporting” service for whole-genome sequence data. Like the Salzberg Screen, GenomeQuest utilizes a software-based approach to analyzing already existing whole-genome or whole-exome sequence data. Unlike the Salzberg Screen, however, GenomeQuest’s product is explicitly commercial and intended for clinical diagnostics, including hereditary breast cancer.

A common motivation in each case is a desire to reduce the cost of diagnostic testing, and particularly of BRCA testing. The cost of Myriad’s BRACAnalysis test in the United States varies somewhat by payer but is generally in the $3,000 to $4,000 range (Myriad actually raised the cost of its test by several hundred dollars after last spring’s district court ruling invalidating a number of its key BRCA patents), with the possibility of significant additional costs where follow-up testing is needed.

The expectation among Myriad’s competitors, including commercial offerings from NewGene and GenomeQuest, is that next-generation sequencing can significantly reduce cost (as well as turnaround time) while maintaining or even increasing the accuracy and degree of coverage. NewGene, for example, has reported a median test cost of under $1,000. Similarly, GenomeQuest has touted the ability of its product to “perform every known genetic test in the GeneTests compendium in one single protocol that costs about as much as a single genetic test,” echoing a point we (and plenty of others) have been making for years: there is a fundamental tension between the falling cost of whole-genome sequencing and the continuing high cost of single-gene diagnostic tests.

Is a Commercial Confrontation Brewing? Not all of the recent developments in BRCA testing represent a near-term, or even a long-term, commercial challenge to Myriad’s business. But developments which appear first in the pages of scientific journals or, as in the case of the Ghent and Leeds tests, in the University hospital setting, are certainly capable of showing up in commercial offerings before long. More immediately, NewGene’s stated intent is to expand its test’s availability beyond the United Kingdom to the rest of the European market and, ultimately, to come to the United States. GenomeQuest, of course, is already available in the United States.

So what about Myriad? For the moment, Myriad remains the exclusive commercial provider of targeted BRCA diagnostic testing in the United States. A major concern, however, is the company’s extreme reliance on the sales of a single product (BRACAnalysis) in a single market (the United States). Thus far, Myriad has achieved comparatively modest success developing a market for its other products (which include diagnostic tests for colorectal and uterine cancer, melanoma and pancreatic cancer) within the United States and for any of its products (including BRACAnalysis) outside of the United States. Currently, BRACAnalysis testing accounts for a striking 88% of the company’s nearly $400 million in annual revenues, with only 2% of those sales occurring ex-US. Myriad’s limited geographic reach, its heavy reliance on BRACAnalysis testing and current and projected competition from a growing array BRCA testing providers utilizing next-generation sequencing represent several of the key factors which caused Goldman Sachs to initiate its coverage of Myriad Genetics last month with a “Sell” rating (pdf).

Myriad, for its part, has taken some steps to address these concerns, in particular by seeking to expand its presence in Europe. Last July, the company created a new position—Executive Vice President of International Operations—in support of what Myraid’s CEO Peter Meldrum declared was the company’s “goal of building a significant presence in Europe by the end of 2012.” The subject of Myriad’s European expansion surfaced again this past January, with Meldrum making several intriguing remarks to investors during a routine earnings call. First, Meldrum indicated that Myriad plans to set up a central lab in Germany to process BRCA samples from all across Europe. That represented a change in plans from July’s announcement in which the company declared its intent to pursue its international strategy on a country-by-country and product-by-product basis—a necessity, given that each country has its own healthcare and reimbursement system.

A Change in Myriad’s Patent Policy? But the real eyebrow-raiser came when Meldrum was asked about Myriad’s patent enforcement policy as it seeks to enter the European market. Meldrum’s response: “if I had my druthers, I would not want to go into a new market in a heavy-handed fashion trying to enforce patents.” He suggested that Myriad might choose instead to rely on its “other competitive advantages that may make such [patent] enforcement unnecessary.”

The exact status and strength of Myriad’s patents in Europe has been cause for uncertainty for quite some time now. Myriad’s five European patents were narrowed significantly by the European Patent Office (EPO) several years ago and, as a result, are thought to provide less protection than the company’s United States patents (which are themselves under attack). A “European patent” is in fact a bundle of national patents issued by a central authority, the EPO; individual infringement suits have to be brought in national courts, one case at a time, which opens up the possibility of local political influence, as well as considerable delay and expense. Moreover, France, Belgium, and Switzerland all changed their laws in recent years to enable a form of compulsory licensing. They did so with Myriad’s BRCA patents explicitly part of the policy debate and rationale for change. Germany has not yet modified its laws in a similar fashion, and is where Myriad plans to build its base, but any attempt to enforce patent rights there could well precipitate the kind of intense firestorm of criticism that swept Australia when Myriad’s licensee there tried to enforce patent rights in 2008, and led Myriad to offer to revoke one of its Australian patents.

As a result, whatever the infringement analysis when examining a particular European competitor’s offering against Myriad’s European patents (and, as we have noted previously, whether or not next-generation sequencing approaches would infringe Myriad’s patents is not at all clear), the practical prospects for Myriad becoming the sole provider of diagnostic BRCA testing in Europe based on patent enforcement are somewhere between slim and none. Even if Myriad were to engage in a country-by-country patent battle and win far-from-assured victories in each case, the company could still lose the war for payment. Myriad would have to fight on a second front with a variety of national health systems holding the power of coverage and reimbursement decisions.

Which perhaps is what Myriad and Meldrum have recognized in citing the company’s “other competitive advantages that may make such [patent] enforcement unnecessary” in Europe. So just what are these “other competitive advantages”? Meldrum highlighted two for investors: speed and accuracy. Regarding speed, he claimed a two week turnaround time for Myriad versus up to a year for current European tests, although it should be noted that NewGene claims a 4-6 week turnaround for its BRCA sequencing product. With respect to accuracy, Meldrum claimed a 2% rate of finding variants of unknown significance (VUS) at Myriad—which seems low—versus a 30% VUS rate for the European tests—which seems high. In light of these advantages, Meldrum concluded on the January call, “I don’t believe that trying to enforce the patents is either a good idea or warranted at this time.”

So what might all of this mean for Myriad’s near-term commercial plans and patent enforcement policies? One option is to take Meldrum’s comments at face value. Around the world, in the popular press and in the eyes of many patients and healthcare providers, Myriad has been widely criticized for enforcing its patent monopolies with respect to BRCA genes and testing. If Myriad believes it can compete successfully in Europe without relying on its patent monopoly, why risk a further public relations backlash by filing patent infringement suits? In addition, one would think that Myriad’s dealings with the many European regulatory and payment authorities—which are unavoidable and will be difficult in their own right—would be less confrontational without pending patent litigation.

Against this background, Meldrum’s comments might be read as an effort to put a positive spin on the specter of growing concern over the degree of practical and legal protection Myriad’s BRCA patents will provide in the future.

The Point of Patents? But there is another layer of meaning to consider. Suppose that Meldrum is right about Myriad’s huge advantages in speed and accuracy. What explains those advantages? At least with respect to interpreting VUS results, such an advantage would derive, in all likelihood, from Myriad’s vast—and currently proprietary—database of BRCA test data, including VUS data. Data that Myriad generally doesn’t share, at least not anymore.

Until 2004, Myriad contributed VUS data to the Breast Cancer Information Core (BIC) mutation database—and publicly touted (pdf) those contributions. The BIC is an open access resource maintained by the National Human Genome Research Institute (NHGRI) to coordinate the detection, interpretation and dissemination of breast cancer mutation data. After November 2004, however, Myriad stopped depositing additional VUS data into the BIC (and has largely ceased publishing its VUS data in peer-reviewed literature, which would have a similar effect).

With that bit of background in mind, a cynic might read Meldrum’s comments like this:

While exploiting our U.S. patent monopoly over the past two decades we accumulated a unique database of relevant DNA sequence and clinical data. Now our U.S. patents are threatened, and many of them are expiring in the next few years anyway. And our international patents aren’t worth trying to enforce. We run a really efficient sequencing lab, and we’ve spent years getting agreements with hundreds of payers for our main BRACAnalysis test. So our new business plan is to combine production efficiencies and expand payment agreements, leveraging our unique proprietary data to retain US market share and enter international markets.

We take pains to emphasize that here we are speculating and, even if Myriad did go this route, there would be nothing strictly contrary to patent law in its doing so. Still, leveraging a proprietary database from a decade’s patent monopoly would be troubling, and would further damage Myriad’s reputation with patients, healthcare providers and the scientific and policy communities.

Among other things, such a strategy would run contrary—at least in spirit—to a policy against extending patent monopolies beyond their terms. In addition, the hoarding of immensely important clinical data does not seem likely “to promote the Progress of Science and useful Arts”—the Constitutional purpose of the patent system—and would provide ample additional ammunition to critics who claim that the current biotechnology patent landscape fails to properly balance commercial interest against those of science and society.

More practically, the current political climate is characterized worldwide, and especially in the United States, by calls for fiscal responsibility and an increasingly close scrutiny of government expenditures. Nowhere is this more true than in healthcare, where spiraling costs place pressure on national health systems (as well as private insurers) to separate effective modes of care from those which are merely expensive. There is little question as to the efficacy of Myriad’s current BRACAnalysis product. But should the company seek to extend its decades-long patent monopoly by restricting access to clearly relevant medical and scientific data, at a potentially considerable cost to both payers and the healthcare system, Myriad’s current and comparatively narrow patent issues might well take a back seat to more pressing economic and political concerns.

Still, for the moment, all of that is speculation. When it comes to Myriad’s actual plans, our best guess is that even Myriad itself has yet to decide exactly how it will proceed in the coming months. What Myriad does in Europe and/or in the United States will undoubtedly be dictated in large part by continuing shifts in the commercial landscape on both continents, as well as whatever happens next in the gene patent litigation, slated for oral argument at the Federal Circuit on April 4 (pdf).

Stay tuned.

Here in the U.S., the Supreme Court will consider the post-conviction DNA testing landscape in the Texas case of Henry Skinner. Thousands of convicts are requesting new DNA testing in light of the increasing number of exonerations based on DNA evidence. Skinner was convicted 15 years ago of murdering his girlfriend and her two developmentally disabled adult sons. At the recommendation of his attorneys, he declined DNA testing for his trial. Texas courts said he doesn’t currently qualify under a state law that grants DNA testing to some convicts, and federal courts refused to overrule Texas. The last time the Supreme Court considered this issue, in 2009, a divided court decided to let Congress and the state legislatures make the rules. Therefore, rules vary from jurisdiction to jurisdiction as to how requests for post-conviction DNA testing are handled. Perhaps this time the Supreme Court will decide to lay down some firmer ground rules.

[Editor's Note: This post originally appeared at Daniel MacArthur's blog Genetic Future, which is part of Wired Science Blogs.]

We have recently summarized efforts by two state legislatures to design regulatory schemes addressing issues raised by the proliferation of genetic information about individuals. New York’s effort addresses questions of insurance coverage for genetic testing. Massachusetts’ goes much further, calling itself a “Genetic Bill of Rights,”a title that accurately reflects its ambitions. In reviewing both of these proposals we have made the point that state-level legislation is no substitute for a coordinated and long-overdue federal-level approach.

But who will lead that coordinated federal effort? As we wrote recently, since the 2008 publication of a SACGHS report identifying major gaps in the regulation of genetic testing, that committee has been disbanded and no clear successor has emerged to champion these issues at the federal level. Last week, the National Human Genome Research Institute (NHGRI), which was originally created by the NIH to support the Human Genome Project, and is today tasked with advancing the understanding and application of human genomics, updated its long-term strategic plan for the first time since 2003 (pdf). Although a “critical part” of the NHGRI’s mission is the “study of the ethical, legal and social implications (ELSI) of genome research,” the Institute’s new roadmap barely touches upon ELSI issues, and dispenses with “legal and public policy issues” in a single sentence by noting the need for “collaborations.”

The NHGRI’s plan clearly fails to devote sufficient attention to the important role social, political, legal and regulatory factors will play in enabling the Institute’s vision of translating genomic medicine “from base pairs to bedside,” a failing for which it has been criticized. But it is unfair to lay the blame solely at the NHGRI’s feet. The NHGRI is, first and foremost, a scientific body (and its key grants frequently feature important ELSI components), not a regulatory one. And neither its parent, the NIH, nor other federal agencies nor Congress have thus far managed to take meaningful action to address the challenges posed by the 2008 SACGHS report, and by numerous similar private and public reports both before and since.

At a time when House leaders are calling for billions of dollars in cuts to federal agencies, including hundreds of millions from the FDA and more than a billion from the NIH, and then calling days later for deeper cuts still, it is difficult to imagine how the resources will be found to overhaul the legal, regulatory and social structures which support personalized, genomic medicine. After all, the call for billions of dollars which funded the Human Genome Project (HGP), and created the NHGRI, had real sex appeal. As then-President Clinton said, the HGP’s output was “the most important, most wondrous map ever produced by humankind.” But improving informed consent and genetic data privacy, developing more rational and efficient regulatory and reimbursement pathways for personalized medicine or clearing a genomic patent thicket? These are the types of seemingly mundane, tedious tasks that are unlikely to be even noticed by the vast majority of politicians or their constituents, let alone attract such flowery praise.

Yet these reforms are necessary, and they will not happen of their own accord. If the next decade is to be “our generation’s Sputnik moment,” as President Obama claimed in last month’s State of the Union Address, with investments in technology, including biomedical research, unleashing a “wave of innovation,” then we must also invest something in those tedious and detailed processes that make it all function in a complex society. The funding required will be nowhere near the billions of dollars it took to sequence the first human genome. Indeed, at least at the moment, funding may not be the main issue at all.

What is needed, now, is leadership. “Strong” leadership would be good, “creative” would be great, “visionary” would be even better. But at this point we need leadership period. Leadership tasked with examining the policy, legal and social challenges identified by the last decade of human genomics, and suggested by the coming one, and developing – and ultimately implementing – comprehensive reforms to meet those challenges at a national and international level. With SACGHS disbanded and the NHGRI focusing elsewhere, it is increasingly clear that a new source of leadership is needed. What remains unclear is what, or who, will fill this role.

[Editor's Note: This post originally appeared as a

Last week, New York State assemblyman J. Gary Pretlow introduced the descriptively named “act to amend the insurance law, in relation to requiring coverage for genetic testing in accident and health insurance polices.”

While not accompanied by a press release, or widely covered by media outlets, the bill merits close attention. While the substance of the bill is striking, its greater import lies in what it reveals about the United States’ current framework for personalized medicine regulation and in what the bill portends for the future of personalized medicine innovation and investment in this country.

The Basics and Breadth of the Pretlow Proposal. Despite its broadly worded title, New York bill #A02325 has a specific goal: to require insurance companies to “provide coverage for genetic testing” for any individual who, “in the opinion of an attending physician, [is at] significant risk of contracting cancer.”

Though not discussed in the text of the bill of itself, the bill’s accompanying memorandum clarifies an intent to specifically require insurance companies to reimburse the cost of genetic tests for individuals deemed to be at significant risk of developing breast cancer (more on this below). With the new legislation, at risk patients “will be able to seek genetic screening and counseling that will be paid for by insurance.”

Whether the bill would require coverage for genetic tests aimed at any type of cancer (as the bill’s text implies), or only for breast cancer (as the explanatory memorandum indicates), its scope is significant. In addition to requiring insurance companies to provide coverage for these genetic tests, it would also require insurers to cover “any subsequent treatment resulting from the results of such test” (emphasis added).

Remember: It’s Only a Bill. Before we go any further, it is important to clarify that this is an introductory legislative proposal. Assemblyman Pretlow has attempted, unsuccessfully, to introduce similar insurance mandates in the past and his current attempt has only been read once and referred to the assembly’s Committee on Insurance. It is not the law of the State of New York. It is not even up for a vote.

Whatever the factors that prompted the bill’s introduction, it would seem to stand little chance of passing in its current form. A primary substantive objection is the exceedingly vague scope of the bill as presently drafted. Assemblyman Pretlow’s proposal does not specify the nature of the genetic tests for which insurance coverage would be required. For example, would it cover multiplex or whole-genome sequencing to identify all identified genetic markers of cancer susceptibility, or only more narrowly tailored susceptibility tests (e.g., Myriad Genetics’ BRACAnalysis)? Similarly, the bill fails to circumscribe the extent of “subsequent treatments” which must be covered by insurers. Would coverage extend to genetic counseling and/or other preventative measures, such as an elective mastectomy in the case of breast cancer, or would it be broad enough to encompass subsequent (and far more costly) therapeutic treatments in the event a cancer materializes?

These and other questions demand significant clarification. Meanwhile, preliminary reaction from the insurance industry has been strongly negative, suggesting that the likelihood of Assemblyman Pretlow’s proposal passing is slim, at least in its current form. But because of what it reveals about the state of personalized medicine regulation in this country, and what that implies about the future of personalized medicine globally, it is a bill that is noteworthy by virtue of its mere proposal.

A Local Solution; A National Problem. In 2008, the now-defunct Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) published a comprehensive review of the “U.S. System of Oversight of Genetic Testing” (pdf). The 276-page report, which remains the most comprehensive analysis of its kind to-date, identified “significant gaps in the U.S. system of oversight of genetic testing that can lead to harms,” including incomplete, inconsistent and overlapping regulations at the state and federal level.

Nearly three years later, little has changed. As we wrote earlier this month, even as the number of genetic tests and other personalized medicine technologies and treatments proliferates, and despite significant talk about overhauling numerous aspects of this regulatory framework – from the NIH’s proposed Genetic Testing Registry to the FDA’s proposed oversight of Laboratory Developed Tests, among numerous other proposals yet to be implemented – the regulation of genetic tests, and of personalized medicine more broadly, continues to remain a messy, patchwork affair.

While regulators and regulated companies struggle to make sense of the current landscape, genetic testing has garnered increasingly high-profile media and political attention in several areas, including the viability of direct-to-consumer (DTC) genetic testing and the patentability of the DNA sequences and methods underlying certain genetic tests. As these issues remain unresolved – the Myriad litigation, for example, is now nearly two years old, and a resolution unlikely to arrive soon – the pressure on lawmakers to act continues to grow.

For example, one the key allegations raised by the Myriad plaintiffs in their initial complaint (pdf) was that Myriad Genetics’ patents on two key breast cancer genes (BRCA1 and BRCA2) mean that “many women at risk [of breast cancer] cannot even be tested because they are uninsured and/or cannot afford the test offered by Myriad.” It is hardly a stretch to view Assemblyman Pretlow’s proposal as a direct, legislative response to perhaps the most politically salient issue posed by the Myriad litigation.

A National Problem; A Global Shift? Taken purely from the perspective of women at risk of hereditary breast cancer who happen to live in New York state, Assemblyman Pretlow’s proposal to require insurance coverage of applicable genetic tests is a positive development. But viewed through a broader lens, the Pretlow proposal is symptomatic of a troubling and ongoing trend: the use of legislative band-aids (e.g., insurance coverage mandates) in an attempt to mitigate the effects of deeper and more serious problems in our personalized medicine regulatory framework.

While significant for a subset of individuals, a bill which would create separate insurance coverage criteria for a subset of genetic tests and follow-on services in a single state would further complicate the existing personalized medicine landscape for national insurers, healthcare providers, genetic test developers and patient advocacy groups. Far from addressing the problems identified by SACGHS three years ago, it would make them worse.

Continued legal and regulatory development in this direction could be tragic for personalized medicine – both the industry and the patients it seeks to serve – in the United States over the long run.

Last week, the global consulting firm PwC published its Medical Technology Innovation Scorecard. The full report (pdf) evaluates the capacity and capability of nine key countries, including the U.S., for medical technology innovation. One of PwC’s key findings was that “the medical technology innovation ecosystem, long centered in the United States, is moving offshore.”

According to PwC there are a number of reasons why this is happening, including the increasingly labyrinthine United States regulatory system:

The citizens of countries with more efficient and less uncertain, capricious and complex regulatory approval processes will gain earlier access to innovative medical technology, and providers in those countries will benefit from more experience in using new devices…Countries with long, complex, arbitrary, nontransparent, costly approval pathways will discourage entrepreneurs and investors, causing them to launch new products elsewhere.

The PwC report made a splash when it was released last week, in part because it attempted to quantify what SACGHS and so many other advisory groups, executives and investors both before and since have noticed: bringing medical and healthcare innovation to market in the United States is an increasingly time-consuming, expensive and frustrating process.

As Luke Timmerman of Xconomy notes, although the United States may not be moving in the right direction, its fall from the top of the heap is hardly inevitable. Timmerman suggests that a few strategic “policy moves could be enough to keep the U.S. in the lead of med-tech innovation for a long time.” That’s probably correct, but it’s important that those moves are timely made.

It is becoming increasingly clear that the regulatory, reimbursement and intellectual property structures that both support and constrain personalized medicine innovation and commercialization in this country are all in need of a strategic and comprehensive overhaul.

The PwC report is a reminder that this overhaul must come relatively soon if it is to head off a significant and long-term shift in the geographic center of gravity for personalized medicine innovation and investment. And the Pretlow proposal, no matter how well-meaning, is a reminder of the “uncertain, capricious and complex” legal and regulatory framework that will continue to frustrate personalized medicine innovation in the meantime.

1. Will the $1,000 genome live up to the hype?

2. Will personal genomics stay DTC?

3. How will the ongoing gene patent debate affect the progress of personalized medicine?

4. When and where will the next regulatory shoe fall?

5. Who will control the data?

A year later the question that comes first to mind is, has anything really changed?

The short answer is no, not fundamentally, although that is not meant to imply that nothing of note happened in 2010. Far from it, as significant legal, regulatory, policy and technological developments continued to reshape the personal genomics landscape.

With that in mind, we welcome 2011 with a look back at the year that was, and a look ahead at what to expect from 2011 and beyond.

The $1,000 Genome. With the draft human genome sequence turning 10 this past year, numerous media outlets reflected on the contributions of genomics and personalized medicine over the past decade. A frequent focal point – and measure of success – was the march toward what Keith Robison has termed the “arbimagical goal” of the $1,000 genome. Companies and investors continue to be enamored of low-cost, high-throughput genome sequencing, as evidenced in part by the IPOs of Complete Genomics and Pacific Biosciences this past fall.

At the same time, as we’ve written previously, the goal is not inexpensive genomics, but personal genomics. What matters is not how much it costs to generate a genome sequence (i.e., raw data), but what you can do with that genome once you have it. Thus, genomics is only personal once both the data and the interpretation are individually tailored.

2011 seems likely to be the year in which we finally crack the $1,000 barrier for a data-only genome, driven in large part by continued advances in sequencing technology, including Ion Torrent’s new Personal Genome Machine. But interpreting the data is another story. Already the dominant meme of 2011 is: “$1,000 genome; $100,000 analysis?”

If you’re waiting for a $1,000 genome delivered by your doctor, complete with advice about how to use the data to improve your health, Matthew Herper of Forbes advises you not to hold your breath. Likewise, analyst Amanda Murphy of the investment firm William Blair, believes that “the wide-scale incorporation of whole genome sequencing into the clinical realm is 10 or more years away.” Herper, Murphy and others think interpreted, clinical-grade genomes are going to remain elusive and expensive, particularly in the short-term and certainly for 2011. At Genetic Future, Daniel MacArthur largely agrees, but notes that for consumers willing to take more of a do-it-yourself approach, a $1,000 genome is a distinct and near-term possibility.

By 2012, motivated do-it-yourself (DIY) genomics pioneers like MacArthur will be able to locate cheap data and free or nearly-free tools to help make sense of that data for around $1,000 (not counting their own labor costs). And patients with an acute clinical need, particularly sufferers of cancer and certain rare diseases, will find that genomics plays an increasingly important role in their care, with insurers or even researchers or healthcare providers bearing the brunt of the cost.

However, the majority of us – non-scientists and generally healthy – are likely to find that full-genome sequences continue to remain just out of reach. With the combined cost of obtaining both complete genomic data and a layperson-accessible, reasonably accurate and personalized interpretation of that data remaining well north of $1,000 through 2011 and beyond, the number of consumers who choose to plunge into their full genomes will remain comparatively small. Most individuals will opt to dip their toe in the gene pool, paying several hundred dollars for a more modestly-sized chunk of personalized genomic data (e.g., the 1,000,000+ SNPs genotyped and analyzed by the likes of 23andMe) while they wait for either a clinical (and reimbursable) need to sequence or the cost of an interpreted personal genome to fall further.

As Yogi might say, the $1,000 genome may arrive this year, but it will still cost more than a grand, at least for most of us.

DTC Personal Genomics. For many, “personal genomics” is synonymous with “direct-to-consumer (DTC) genomics.” But despite the continued decline in the cost of genomic data, we begin 2011 with fewer significant providers of DTC genomic services than at the start of 2010.

The major developments have been covered extensively here at the Genomics Law Report. From the Pathway/Walgreens kerfuffle (and the FDA’s response) to the Congressional hearing and critical GAO report (and the FDA’s response), 2010 was certainly a tough year in Washington for DTC companies. (For a complete recap see: The Past, Present and Future of DTC Genetic Testing Regulation.)

While some erstwhile DTC providers (in particular Navigenics and Pathway Genomics) have, at least for the time being, shelved the consumer-facing side of their business, others continue to push forward. 23andMe remains the DTC front-runner, recently raising funds from both venture capitalists and the National Institutes of Health, but a handful of other DTC providers (including deCODE genetics) continue to offer products while a new generation of DIY genomics companies and researchers strive to put genetic data directly into the hands of increasingly large numbers of individuals.

For all of the apparent interest in DTC genomics from Congress and the FDA, the reality is that neither has yet articulated a clear plan to regulate that industry and, at the same time, both lawmakers and the regulators have bigger fish to fry in 2011. DTC personal genomics providers and their tests represent a mere fraction of the laboratory developed tests (LDTs) the FDA has vowed to regulate more aggressively and expansively than ever before (more on this below).

More importantly, the market for DTC personal genomics pales in comparison (at least in terms of market size and clinical importance, although perhaps not necessarily media coverage) to a host of other pressing issues facing Congress, the FDA and other regulatory agencies in 2011. These include, in no special order, the development, regulation and reimbursement of companion and other advanced diagnostics, follow-on biologics, how to deal with a rise in genomic data in regulatory submissions and what to do about whole-genome sequencing in particular and, of course, the fate of the healthcare reform legislation.

Remember, too, that following the recent mid-term election there will be personnel turnover in Washington as well. To cite two examples: the FDA’s No. 2 official, Joshua Sharfstein, has already resigned and one of the most vocal critics of DTC genetic testing during last summer’s House hearing, Congressman Parker Griffith – who compared providing genetic information to consumers with throwing live snakes into a crowded hearing room: useful only to incite panic – failed to win reelection.

Stepping back to view the prospect of DTC genetic testing regulation through this broader lens helps explain why, despite continuing uncertainty and ominous regulatory overtures, the DTC industry is likely to survive 2011 intact. Just as it did in 2010.

That is not to say that industry will not face increased scrutiny in 2011; or that this would be a bad thing.

There continues to be a clear need for more industry transparency, as well as heightened regulation of the advertising and marketing practices of existing genetic testing companies. The arrival of the NIH’s genetic testing registry (GTR), although not without its own critics, remains slated to arrive this spring. The GTR, along with increased enforcement of existing regulations from agencies like the FDA and the FTC, could do much to put a halt to true consumer abuses in the DTC personal genomics market.

There is also a widespread recognition that the DTC industry would benefit from greater standardization. A primary need is for greater definitional clarity. Terms like “DTC genomics” and “DIY genomics” frequently receive user-defined and inconsistent definitions, and no regulation – whether government- or self-imposed – will be practical until this terminological confusion is resolved. More substantively, there is a clear need to develop data standards, including both a standard format for returning genomic data as well as for interpreting and reporting those data. While DTC companies have frequently expressed interest in pursuing the latter, including in cooperation with federal agencies, considerable progress in all of these areas still needs to be made.

Of course, while unlikely, it remains a possibility that regulators or lawmakers will succeed in directly regulating DTC personal genomics in 2011. This could happen as part of the broader LDT regulatory movement or, more likely, take the form of narrower and more targeted regulatory requirements, such as interposing a physician or genetic counselor between the company and consumer at the ordering and/or data delivery stage. Or the FDA could always come up with some other out-of-the-box approach to DTC regulation.

Nevertheless, as we enter 2011 it remains legal throughout most of the United States to provide healthy individuals with direct access to their personal genomic data. While that is not the case worldwide, technological innovation and the proliferation of genomic data and of DIY genomic tools will drive continued growth and diversification of the DTC personal genomics landscape in the United States in 2011 and beyond.

Gene Patents. Without question, last year’s biggest story was – and continues to be – the ongoing Myriad gene patent litigation. Judge Robert Sweet’s jaw-dropping district court decision invalidated Myriad’s challenged patents across the board, for the moment, and thrust the debate further into the public and political spotlight than ever before.

While we entered 2010 anticipating a decision in Myriad, as well as in other important litigation (notably Prometheus and Bilski), we wrote that “there is little reason to believe that 2010 will be the year that the gene patent question will be finally resolved.” And we’re fully prepared to say the exact same thing in 2011 (and possibly in 2012, as well).

Those who first caught wind of the gene patent issue in March of 2010 (when Sweet’s opinion issued) may find it inconceivable that by the end of 2011 – a full 21 months later – there could be no resolution. But courts move slowly, and with the Supreme Court choosing once again to ignore biotechnology patents (the Supremes issued a heavily hyped Bilski opinion that proved to be just hype, and little more), the Federal Circuit rehearing Prometheus and saying exactly what it said in 2009 and the Myriad litigation in all likelihood multiple appeals from reaching its conclusion, a definitive answer does not appear imminent. Those waiting on the courts to resolve the patentability of genes or the increasingly important diagnostic methods at issue in Myriad, as well as Prometheus and Classen, are going to be forced to keep waiting.

Still, just as in 2010, 2011 will see its share of high-profile gene patent opinions issuing from courts. The most eagerly anticipated is the Federal Circuit’s Myriad opinion, which is expected in late spring or early summer. But the likelihood that Myriad or any other legal opinion will bring substantial and lasting clarity to the patentability of genes and related diagnostic methods in 2011 is slim.

However, not all parties are likely to be content to sit idly by and wait for the courts to decide (or not) the issue of gene patents. 2010 saw the publication of the highly publicized and equally controversial SACGHS report on gene patents and licensing. The report sparked plenty of conversation in biotechnology industry and policy circles and, though the SACGHS was disbanded later in 2010, those conversations have not quieted (as evidenced, in part, by the Justice Department’s unexpected amicus brief in Myriad). As genomic sequencing and diagnostic tools play an increasingly prominent role in clinical care, the role of patents – as either facilitators or inhibitors of personalized medicine innovation – will come under increasing scrutiny.

Persistent patent uncertainty continues to be a challenge for biotechnology companies and their investors. In large part for that reason, many are actively seeking out alternative pathways through the increasingly thorny gene patent thicket. Thus, don’t be surprised if 2011’s most noteworthy gene patent developments happen outside of the courtroom.

Legislation and Regulation. There was a lot of talk about regulating genetic testing in 2010, but the most significant regulatory action occurred late in the year with the EEOC’s publication of final regulations for Title II of the Genetic Information Nondiscrimination Act (GINA), which finally took effect this past week. With the increasing proliferation of genetic information, expect to see GINA – now in its third full year as law – in the headlines with more frequency in 2011.

As for genetic testing regulation, yes, 2011 could be the year that the FDA implements sweeping regulatory changes for laboratory developed tests (LDTs), including most genetic tests. But after announcing its intent to do just that back in June, the second half of 2010 came and went without significant follow-up activity from the FDA. After watching the FDA attempt to regulate a subset of LDTs (in vitro diagnostic multivariate index assays, or IVDMIAs) for four years before sending IVDMIA regulation to the regulatory trash heap for good late in 2010, there is good reason to be skeptical.

There’s a reasonable likelihood that the FDA will offer at least one concrete proposal for an LDT regulatory framework in 2011. But don’t expect that proposal – whatever its particulars – to be embraced by regulated entities, and we certainly wouldn’t bet on the FDA being able to finalize such an initiative and produce final guidance (or regulations, depending on which way it chooses, or is forced, to proceed) in the same year.

Other possibilities include two oft-discussed pieces of personalized medicine legislation, the Genomics and Personalized Medicine Act (GPMA) and the yet-to-be-introduced bill from Senator Hatch on advanced personalized diagnostics. But as we sit here today, the most likely scenario is that 2011 will bring no significant new final legislation or regulation affecting genomics and personalized medicine.

Such a rapidly-moving field poses substantial challenges for overburdened lawmakers and regulators even in the best of political environments and 2011, with its newly divided Congress and promise of contentious battles over healthcare reform and other key issues, hardly qualifies as an ideal political environment. Never say never, but those who would bring legislative and regulatory change to personal genomics are likely to spend 2011 primarily laying the groundwork for 2012 and beyond.

Access and Control. Our final question last year continues as perhaps the most important of 2011: who will control the data?

All of the issues above – from how much a genome will cost to who will be able to purchase one and whether a company can patent parts of it – reflect concern with access to and control of genomic data. Laws like GINA protect the use of genetic information in certain contexts, but at present there is no federal genetic privacy law and little consensus on whether an individual owns her own genetic material and data once it leaves her body.

As courts and legislatures continue to wrestle with these issues across an increasingly broad range of factual backgrounds – from state-mandated testing of newborns for genetic disease to the use of forensic DNA to monitor an increasingly broad subset of the country’s criminal (and frequently non-criminal) population – the pressure to clarify the rights individuals have in their genomes will intensify. Will we (along with courts and legislatures) conceptualize genomic data primarily as personal, with the individual the locus of control, or as medical, routing access and interpretation through the healthcare system?

Other challenges of no less importance will continue to demand attention in 2011 and beyond. We have already discussed, above, the issue of access to personal genomic data, and, indeed, no less an authority than NIH Director Francis Collins has written that “free and open access to genome data has had a profoundly positive effect on progress.”

But even as we strive to maintain broad and individualized access to genomic data, we will simultaneously need to ensure that those without the means (financial or otherwise) or desire to pursue their own genomic data are still able to benefit from personalized genomics. Among many, many challenges, this will require continuing the uphill battle to retrofit a healthcare system populated with institutions and individuals largely unprepared to handle the increasing size and complexity of incoming genomic data.

We Will Finish Where We Started. Again. These are big challenges, and they will not be met in full in 2011. We are confident that, when 2012 rolls around, most (and perhaps all) of the same issues will present themselves yet again to the field of personal genomics.

The $1,000 genome will continue to remain more hype than reality for most individuals. DTC personal genomics will continue to spark concern from legislators and regulators, tantalizing unscrupulous businesspeople even as it is embraced by an increasingly broad segment of the population. Gene patents will remain an unsettled area of law, even as public and private efforts to resolve the issue progress. The specter of FDA regulation will continue to loom large—and advance slowly. And, most importantly, while more people than ever before will have affordable and largely unfettered access to their genomic data, that access will be uneven, with many who could benefit most from personal genomics denied that opportunity.

Still, even as personal genomics’ challenges remain largely the same today as they were in 2010, and likely will be again in 2012, progress is apparent. After all that happened in 2010, perhaps all that really changed in the last year is that personal genomics is now a year older, a year wiser and continuing to advance. And perhaps that is enough. At least for 2011.

The first is primarily a curiosity: the allegation that Chinese authorities are spying on deCode Genetics, Iceland’s most prominent genetic research company and provider of the direct-to-consumer genetic testing service, deCODEme. Nobody seems to know exactly what China is looking to gain by clandestinely exploring Iceland’s genetic genealogy. You are welcome to speculate in the comments.

The second raises broader issues: the revelation that the State Department’s ongoing human intelligence collection directives include requests for “biometric information” on key world leaders, including United Nations arms inspectors, the Director General of the World Health Organization (WHO) and key advisors and aides to United Nations Secretary General Ban Ki-moon. A separate cable detailing intelligence collection priorities in Africa’s Great Lakes region clarifies that “biometric information” includes “health [data]…fingerprints, facial images, DNA, and iris scans.”

Not disclosed in the WikiLeaked cables: why the State Department wants the biometric data or whether any have been successfully obtained.

Surreptitious Testing: An Overview. The cables are, however, a reminder that the law surrounding the surreptitious collection and testing of biometric data, including DNA, remains extremely murky.

While the extent to which surreptitious testing is performed in diplomatic and intelligence contexts is not publicly known, such testing is commonplace in law enforcement settings. For example, police routinely collect and analyze “abandoned DNA” during forensic investigations. Indeed, one of the primary indices of the FBI-run Combined DNA Index System (CODIS) is the Forensic Index. The Forensic Index is comprised of DNA profiles constructed from biological specimens from unidentified individuals collected at crime scenes. These DNA profiles are then compared against similar offender and arrestee indices, which are also housed in CODIS, to aid in law enforcement efforts. Several high-profile criminal investigations, including the recent arrest of the “Grim Sleeper” serial killer, have been aided by this technique.

Concerns about surreptitious sampling and testing have also appeared in other contexts. During this past summer’s Congressional hearing on direct-to-consumer (DTC) genetic testing, the Government Accountability Office (GAO) presented results from a series of undercover encounters with DTC companies. One recording appeared to show a company (later identified as Pathway Genomics) encouraging a prospective customer to collect and send in a saliva sample from her fiancé without his consent, in order to surprise him with results of a genetic test.

In 2009, New Scientist reporters Peter Aldhous and Michael Reilly used similar tactics to demonstrate that it was possible to obtain genetic information about someone without that individual’s consent and detailed their experiences in a special investigation: how my genome was hacked.

Shortly after the 2008 presidential election, an article appearing in The New England Journal of Medicine (NEJM) considered the possibility that, by the time the 2012 election rolls around, presidential candidates might be at significant risk of surreptitious genetic testing. The authors worried that “persons or groups opposing a candidate [and] hoping to harm his or her chances for election” would obtain and release genetic information without consent, a form of “genetic McCarthyism.” This would not be very difficult, the authors concluded, since “sufficient DNA for amplification and analysis can be obtained from loose hairs, coffee cups, discarded utensils, or even a handshake.” The WikiLeaks revelations about State Department officials seeking biometric information on world leaders indicate that the NEJM speculation may already be reality on the world stage.

There are numerous other scenarios in which surreptitious genetic testing might be employed to acquire information about less famous but equally unwitting individuals, including to establish paternity or to evaluate a potential romantic partner.

Legal Uncertainty Surrounds Surreptitious Testing. To many, it seems like “there oughta be a law” against surreptitious genetic testing, at least in certain settings. However, as reported last year by the Genetics & Public Policy Center, there are “limited legal safeguards against surreptitious DNA testing or its potential consequences for those subject to nonconsensual testing.”

While the 2008 passage of the Genetic Information Nondiscrimination Act (GINA) prohibits the unauthorized acquisition or use of genetic information in certain contexts (health insurance and employment), it offers only limited protection against surreptitious testing. For instance, while it covers most of the Federal government, including the State Department, GINA does not apply to the military or the VA. It also does not restrict behavior outside of the insurance and employment contexts including, for example, by political adversaries or their supporters during a presidential campaign. (Interestingly, the NEJM article declined to advocate for “laws that would make it a federal crime to sequence a candidate’s DNA without consent,” preferring voluntary restraints and education instead.)

Other Federal statutes, such as the Health Insurance Portability and Accountability Act (HIPAA) may offer protection under certain scenarios (e.g., the use and disclosure of genetic information by covered entities, predominantly health plans and healthcare providers) but, again, fall short of providing a complete and clear prohibition on surreptitious genetic testing.

The 2008 GPPC report also looked at state law to evaluate which states proscribe surreptitious DNA testing (pdf). Determining the exact number of states that prohibit this behavior depends heavily on context. Some state statutes prohibit unauthorized acquisition or analysis of genetic information, while others apply only to unauthorized disclosures. Similarly, some state statutes appear to encompass all manner of genetic information, whereas others cover only certain genetic information (e.g., health-related information) or apply only to certain settings (e.g., employment or insurance discrimination). The National Conference of State Legislatures (NCSL) has also compiled data on state genetic privacy laws and, like the GPPC report, the NCSL data indicates considerable variability at the state level.

In the absence of a comprehensive federal law, state prohibitions are currently the main source of relevant law when it comes to restricting surreptitious genetic testing. But not all states have such laws. Whether surreptitious genetic testing is illegal thus typically depends on a combination of who is doing the testing, whom they are testing, what they are testing for, how they are using the results and, most of all, the state or states in which those activities take place.

Finally, there is a possibility that surreptitious genetic sampling and testing may be prohibited on either common law or constitutional grounds, at least in certain situations. For example, in the Texas newborn blood spot litigation, which we covered earlier this year, the plaintiffs alleged both Fourth Amendment (unreasonable search and seizure) and Fourteenth Amendment (right to privacy) violations resulting from the state’s policy of retaining newborn blood spots for ongoing research without explicit parental consent. While both claims survived summary judgment, and may have helped precipitate the litigation’s settlement, these and other legal theories remain untested in most states and under most circumstances.

What We Should Learn From WikiLeaks. Coming full circle, the leaked State Department communiqués raise important questions to which we do not have clear answers. In particular: under what circumstances is the surreptitious collection of biometric data, including genetic data, appropriate?

For most, the answer to that question will depend to some degree on context. Should State Department officials gathering intelligence abroad have a greater or lesser ability to pursue surreptitious genetic testing than domestic law enforcement agents? Should private individuals be permitted to conduct surreptitious genetic testing in certain circumstances (e.g., to confirm paternity) but not others (e.g., when shadowing a politician or celebrity)?

While individual answers may vary, we expect the law to provide us with clear guidelines. As is made clear by the above analysis, however, there exists a wide range of scenarios where surreptitious genetic testing, should it occur, would fall squarely within a legal gray area.

This is in stark contrast to the situation in other countries. In the United Kingdom, for instance, the Human Tissue Act 2004 made it a “criminal offence to take a sample from someone to test their DNA without their consent, except for medical purposes and lawful investigative purposes” as of 2006. Similarly, while Germany’s new Human Genetic Examination Act (also known as the GenDG) is overly restrictive in many respects, § 8(1) of the GenDG (pdf) clearly prohibits “any genetic examination or analysis” without the “express, written consent of the subject person, both in regard to the respective genetic examination and genetic sample.”

Whether the United States adopts the same approach to surreptitious genetic testing or not, the issue must be addressed. We must articulate, much more clearly than at present, the situations in which unconsented genetic testing, analysis and disclosure is permissible, and those in which it is proscribed.

Each year, the availability of low-cost, high-quality genetic information expands. Along with a wide array of legitimate and beneficial uses, the growing accessibility of this genetic information brings with it an increasing number of opportunities to employ and to abuse surreptitious genetic testing. As we continue to push forward into the era of personal genomics, the time has come to seriously discuss a comprehensive legal framework for surreptitious genetic testing.

The GenDG (pdf) took effect early this year and, until recently, little news of its impact on German law, policy or business has made its way across the Atlantic. Last week, however, several prestigious German scientific academies released a report entitled “Predictive Genetic Diagnostics as an Instrument of Disease Prevention.” The “Academy Group,” as the report’s authors refer to themselves, consists of the Leopoldina, the Berlin-Brandenburg Academy of Sciences and Humanities and the German Academy of Science and Engineering Acatech. Astoundingly, according to a recent editorial in the journal Nature, the report is the first from the group in its 350 year existence.

While the Academy Group’s report “discusses all aspects of genetic testing of healthy individuals to prevent disease, including the medical, ethical, economic and legal dimensions of the issue,” it takes particular issue with the GenDG. In a press release announcing its report, the Academy Group characterized the GenDG as “out of touch with the latest technology, almost impossible to implement in clinical practice” and “in desperate need of amendment.”  The complete report (pdf) is available only in German, but the Academy Group’s summary and twenty-two recommendations (pdf) addressing both genetic testing and the GenDG specifically are available in English.

Reviewing the Recommendations. The Academy Group’s recommendations are informed by a fundamental belief that genetic testing should be focused on helping people “to remain healthy, to regain their health or, at least, to alleviate the consequences of illness.” Although the Academy Group briefly notes, later, that genetic testing “can be advantageous for the life planning of a person,” the clear focus is on clinical utility. Apart from genetic research, no meaningful value is ascribed to other uses of genetic testing and data that appear to have gained much more traction in the United States, the United Kingdom and elsewhere, including ancestry testing, self-experimentation and testing for medical conditions that possess personal utility even if they do not rise to the level of current clinical utility.

An Excess of Information. Another theme that runs through the Academy Group’s recommendations is a concern about an “excess of genetic information” generated by the increasing proliferation of genetic testing and, in particular, whole-genome sequencing. Although some may consider there to be no such thing as too much genomic data, the group’s concern is at least consistent with its core belief that genetic data is valuable solely to the extent of its clinical utility. Given that certain genetic data is acknowledged to be of limited clinical value for many individuals, at least as of today, the Academy Group sees such “excesses” as likely.

Despite its underlying concern about excess genetic data, the Academy Group clearly thinks the GenDG’s nearly complete prohibition on the long-term storage of genetic information takes things a step too far. The problem lies with §12 of the GenDG which requires, with very limited exceptions, the “immediate” destruction of genetic information after 10 years. The Academy Group’s recommendations encourage the GenDG to “take into account the aspects of long-term storage and subsequent analysis of the excess of genetic information” and, if adopted, would specifically remove the flat prohibition on storage of genetic information beyond a decade.

The group’s primary recommendation is reasonable: individuals should be allowed to decide, in conjunction with an appropriate healthcare provider, whether to (a) use such excess information in a specific manner (although no examples are provided), (b) destroy the information or (c) “save [it] for the time being in an unused state.” This would, in effect, allow the individual and her healthcare provider to determine what constitutes “excess of genetic information”, rather than continue the GenDG’s approach of statutorily determining non-clinical genetic data to be excess and thus not valuable.

However, the Academy Group’s recommendation extends only to individuals competent to make such a decision. Children or temporarily incompetent adults should not, according to the Academy Group, be given the option to use or seek to interpret any excess genetic information “because this would take the option of ignorance away from the examined person.” The Academy Group recommends that the information be “saved in a restricted form” until “competency is bestowed”—in the case of a child, at her 18th birthday party—at which point the individual would be allowed to decide for herself.

While the Academy Group’s recommendation with respect to genetic testing of children is more permissive than what appears to be allowed under the current GenDG framework, it is still at odds with practices in other countries where the genetic testing of minors for non-clinical purposes is not expressly prohibited.

Genetic Screening and Unintended Consequences. Several other Academy Group recommendations concern genetic screening at various stages, from preconception (carrier testing) to prenatal to postnatal (newborn screening). The recommendations are consistent with the fundamental approach of requiring testing to be related to medical treatment. This leads to the curious consequence of recommending limitations on testing of an unborn child but, once the child is born, encouraging genetic testing.

While the Academy Group recognizes that “healthy people or couples can be interested in finding out whether they are genetic carriers of any recessive hereditary disease…to assess the health risk of their own child,” the group believes that such carrier screening is not yet ready for widespread medical or commercial use. The group recommends:

For the time being, systematic heterozygote examinations with regard to the health risks for the children of the examined people should only be carried out as part of research projects. They should be embedded in secondary medical, ethical and social research in order to gain experience about the personal and social effects.

While numerous carrier screening providers offer services outside of Germany—both directly to consumers and through licensed healthcare providers—the Academy Group appears to have no interest in seeing Germany following suit.

The group’s recommendation, if adopted, could have the unintended consequence of promoting a new form of “medical tourism,” with some German couples taking a quick trip abroad (e.g., to the United Kingdom) for preconception carrier testing.

When the Academy Group turns to testing of newborns, it is critical of provisions of the GenDG that have the effect of discouraging or interfering with such testing:

The Gendiagnostikgesetz considers the newborn screening as a genetic survey. Accordingly, since the Gendiagnostikgesetz came into force, the parents must be provided with a genetic consultation before blood is taken. Baby nurses and midwives, who previously took the blood, are no longer allowed to do this on their own responsibility. There are already indications that this is leading to the newborn screening not being carried out for some newborn babies. This can lead to life-long disability, which could have been avoided with early diagnosis and appropriate treatment.

The Academy Group’s recommendation in response is sensible: the GenDG “should regulate the newborn screening separately” and, presumably, in a fashion that does not hinder the practice from occurring routinely.

Conflicting Duties. A consequence of the GenDG’s extremely patient-centered and protective approach to genetic testing is that, according to the Academy Group, “without exception” the GenDG “considers confidentiality for patients to be of a higher significance than the medical fiduciary duty towards relatives that have a high risk of developing” a genetic condition. Under the GenDG, doctors are strictly prohibited from discussing genetic information with a relative, even where doing so might have significant clinical utility.

The Academy Group recommends a change in the weighting of these competing duties, saying that “in cases of clear medical benefits” doctors be permitted to balance the importance of individual genetic privacy enshrined in the GenDG against the clinical utility of genetic information to an individual’s relatives. Interestingly, the Academy Group does not propose—as it does elsewhere—a specific modification to the GenDG to enable this exercise of physician discretion, and it remains unclear whether following the group’s recommendation would leave doctors on the wrong side of current law.

The difficulty of balancing the competing duties of individual confidentiality, particularly in the context of genetic information, and the broader utility of genetic information, particularly for an individual’s close relatives, is not a problem unique to Germany or the GenDG. The United Kingdom’s General Medical Council addressed this exact issue last year and reached a conclusion similar to that of Germany’s Academy Group. As this issue continues to show up in a variety of contexts, policymakers—and especially doctors—are likely to continue to struggle to strike the proper balance.

Direct-to-Consumer Testing. Unsurprisingly, the Academy Group’s recommendations also tackle the topic of direct-to-consumer (DTC) genetic testing, which remains one of the most hotly contested areas of genetic testing regulation and policy as we head into 2011.

As we noted last year, the GenDG arguably already prohibits all DTC genetic testing. Nevertheless, the Academy Group expresses concern about the “uncertain scientific basis” of DTC tests, as well as with the possibility of surreptitious testing. Seeking to make the GenDG’s likely DTC ban explicit, and consistent with the Academy Group’s emphasis on clinical utility in genetic testing, the group recommends that DTC tests “not be permitted because they do not fulfill the requirements of medical and ethically acceptable predictive genetic diagnostics.” (The Academy Group also offers a separate recommendation banning all DTC advertising for genetic tests.)

The unfavorable outlook of legislators and policymakers toward DTC genetic testing is hardly restricted to Germany. In the United States, a report issued by the Government Accountability Office (GAO) over the summer was sharply critical of DTC genetic tests—although critics of the GAO report’s methodology and conclusions abound—and the Food and Drug Administration (FDA) is preparing to regulate all laboratory developed tests (LDTs), including DTC genetic tests. (For a more complete overview see The Past, Present and Future of DTC Genetic Testing Regulation.)

A Global Perspective. Finally, the Academy Group exhibits at least a partial recognition that Germany’s approach to genetic testing may not be perfectly aligned with the rest of the world.

The Academy Group’s sixth recommendation acknowledges that German laboratories often receive samples from abroad and, were the GenDG to be strictly applied, it might operate to significantly curtail the foreign business of German companies in light of the substantial consenting requirements imposed by the GenDG (among its other provisions). In recognition of this issue, the Academy Group recommends that:

The genetic analysis of a sample acquired abroad by a German laboratory should be acceptable if the doctor that has sent the sample confirms that the person concerned has been provided with information about the being, scope and significance of the genetic examination in accordance with the legal regulations in the sample’s country of origin and the person concerned has subsequently granted his consent.

Quite sensibly, the recommendation appears to permit German laboratories to process samples for diagnostic testing if the submitting doctor verifies that the sample is being sent in compliance with the laws of the sample’s country of origin.

Note, however, that other restrictions imposed by the GenDG appear to remain in place. Given the broad limitations the GenDG imposes on genetic testing products and services, including on both the circumstances in which testing may occur and the type of analyses which may be conducted, it seems likely that, even if this particular recommendation is adopted, German laboratories and genetic testing providers will struggle to offer the same suite of products as their international competitors. If the Academy Group’s aim is to ensure that German laboratories remain competitive at the global level, its recommendations will likely need to be broadened.¹

Other Recommendations. The remainder of the Academy Group’s recommendations echo those made by the vast majority of policy groups to review the issues surrounding the development and adoption of genetic testing. These include a need for (a) more research into the genetic bases of complex traits and the cost-effectiveness of existing technologies and services, (b) more specialists in human genetics and more effective training in genetics for existing medical professionals, (c) a renewed focus on translational research and (d) improved public and educational outreach concerning the “possibilities and limits of genetic medicine.” All of these goals are laudable and, at this point, none are surprising.

What’s Next for Germany? It remains to be seen whether some or all of the Academy Group’s recommendations will be adopted by German lawmakers. Of particular interest are those recommendations that require, explicitly or implicitly, revisions to Germany’s just-passed GenDG legislation.

However, even if all of the group’s recommendations are adopted, GenDG will continue to stand as one of the most restrictive and, yes, paternalistic pieces of genetic legislation passed by any country to date. As other countries continue to grapple with how to appropriately regulate genetic technologies, including genetic diagnostic products, Germany’s experience with the GenDG may serve as a test case for one approach.

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¹ We are unaware of the effect, if any, that the GenDG is currently having on German biotechnology companies, entrepreneurs and investors, but would welcome feedback from our readers on this point.