Social Media as a Research Tool. Last month, PatientsLikeMe, an online patient community, made headlines with a study published in Nature Biotechnology in which the company analyzed self-reported data from nearly 600 patients to demonstrate that the use of lithium had no effect on the progression of amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease).

The study’s findings are valuable for ALS patients, who frequently experiment with unproven treatments in an attempt to slow progression of the degenerative disease for which there is not yet an effective therapy. But the long-term impact of the study’s methodological approach, which suggests “that data reported by patients over the internet may be useful for accelerating clinical discovery and evaluating the effectiveness of drugs already in use,” should be felt far beyond the ALS community.

PatientsLikeMe was formed after the brother of two of the company’s co-founders was diagnosed with ALS. The company, which initially sought effective treatments for ALS, has broadened its focus in recent years. PatientsLikeMe now seeks to help patients representing a range of diseases manage those conditions and to help medical researchers and companies improve the way they develop treatments, including by involving both patients and social media.

The Nature Biotechnology publication is a validation of the company’s efforts and, while not a substitute for traditional clinical trials, the PatientsLikeMe approach does demonstrate that social media tools, including networks of like-minded individuals (in this case ALS patients) “can provide supplementary data to support effective decision-making in medicine and discovery.”

Or, as PatientsLikeMe Chairman and Co-Founder Jamie Heywood told Health Business Blog, the study affirms that “there is tremendous value in reconnecting researchers to the patients they are working hard to serve by changing the norm from doing research ON patients to doing research WITH patients.”

Joining the Revolution in Progress. The PatientsLikeMe study, while impressive, is just the latest development in an ongoing and increasingly widespread effort to change how personalized medicine is pursued.

Consider, for example, Hugh Rienhoff, who launched a search to find the cause of his daughter’s mysterious genetic condition and, along the way, created a non-profit company to help others tackle similar problems. Or Genomera, a Bay Area start-up which aims to provide tools to help individuals design and carry out their own, personalized research projects.

Or 23andMe, the most prominent direct-to-consumer (DTC) genetic testing company in the market today, which has already demonstrated its ability to use social media and customer-driven data to identify novel genetic associations. While those particular associations are of admittedly limited utility, 23andMe is employing the same approach to identify the causes of – and potentially a cure for – Parkinson’s disease, a disease for which Sergey Brin, the Google co-founder and the husband of 23andMe co-founder Anne Wojcicki, carries a genetic predisposition.

23andMe also recently opened recruitment for a new study, in conjunction with researchers at Stanford University, to examine how social networking impacts health behavior and research.

And there are plenty of other projects seeking to expand the role individuals and social media play in scientific and medical research, including the Personal Genome Project, Sage Bionetworks, CollabRx, Genetic Alliance and DIYgenomics, to name just a few.

A Revolution Hiding in Plain Sight. While companies like PatientsLikeMe and 23andMe have successfully leveraged social media tools to demonstrate alternative pathways for personalized medicine research, social networking alone would be insufficient to produce a true revolution in personalized medicine. Another key factor has been the dramatic increase in availability of personalized health data, particularly genomic data.

Over the past year, a spate of articles has appeared in mainstream media publications describing the alleged failure of the Human Genome Project (HGP) to live up to the lofty expectations it set for itself a decade earlier. Last fall, for example, The New York Times’ Nicholas Wade lamented that “ten years after President Bill Clinton announced that the first draft of the human genome was complete, medicine has yet to see any large part of the promised benefits.” Francis Collins, then one of the leaders of the HGP and now the head of the NIH, opined in the journal Nature that “while the promise of a revolution in human health remains quite real…it is fair to say that the [HGP] has not yet directly affected the health care of most individuals.” And Matt Ridley criticized the HGP and its successors in the pages of The Wall Street Journal for “underdelivering useful medical knowledge and overdelivering other stuff.”

Yet by focusing solely on more easily quantifiable scientific and medical advances, and dismissing all of the “other stuff,” Wade, Collins, Ridley and others have largely overlooked a crucial legacy of the HGP: the rapid and continued democratization of genomics. Over the past ten years, technological advances have made it possible for increasingly large numbers of researchers, clinicians, patients and consumers to access personal genomic data. What was once a decade-long, multi-billion dollar, public-private collaboration to obtain a single human genome now requires nothing more than a credit card, a saliva sample and a few weeks.

While there can be no doubt that the ultimate goal is an improved understanding of the mechanisms of human disease and, as a result, an improved ability to effectively and efficiently treat those diseases, we should not lose sight of the tremendous progress we have made over the past decade in democratizing genomics and changing how personalized medicine is pursued.

Last fall, in “The Failed Promise of Genomics,” Matt Ridley wrote that “…personalized genomics will struggle to say anything at all, for the simple reason that it will be too personal.” That argument never made much sense to me in large part due to one simple fact, which was beautifully articulated by Joe Pickrell of Genomes Unzipped in a post explaining why DTC genetic testing is good for research. Wrote Pickrell, “all research is driven by curiosity, and the people most curious about a disease or trait are those who have it.”

The dramatically increased personalization of many aspects of health and medicine, especially genomics, is one promise the HGP has delivered in spades. As for Ridley, after initially worrying that personalized genomics was somehow too personal, he finally decided to see for himself. Apparently prompted by the threat of FDA regulation of DTC genetic tests, Ridley recently opted in to the personalized genomics movement and appears to have come away a changed man.

Last month, writing again in The Wall Street Journal, Ridley argued that the promised genomic revolution may indeed be realized, but only if it is embraced by the masses. “Genetic knowledge, whether the high priests like it or not, is going to be a crowd-sourced phenomenon,” Ridley wrote.

Of course, as the work of PatientsLikeMe, 23andMe and others continues to demonstrate, the revolution has been ongoing for some time now. Ridley is right that it will take many more doctors, researchers, consumers, patients, policymakers and, yes, even pundits before the active involvement of individuals in personalized medicine research becomes commonplace. And he is right that the revolution will occur whether or not personalized medicine’s “high priests” – including groups like the American Medical Association – are ready for it. What Matt Ridley failed to grasp is that the revolution is already here, and now he is a part of it.

Welcome to the Revolution, Matt.

What We Learned from the Myriad Oral Argument. For all of the attention focused on the Myriad oral argument, most spectators have only one very practical question: did Monday’s argument provided any meaningful clues with respect to how the Federal Circuit might rule on appeal of the lower court’s startling ruling?

In a word: no. In a few more: we learned nothing from the Myriad argument that leaves us better able to predict how the Federal Circuit will rule in this case.

That may be unsatisfying for researchers, businesses, investors, academics and many others who, having tracked the litigation since its inception, are anxious for a resolution, but it should not come as even a mild surprise.

First, as John noted last week, it is dangerous to read too much into any oral argument. While an oral argument can be a balance-tipper in a close case, there’s no guarantee that a written judicial opinion will resemble the prior courtroom conversation.

Second, and more importantly, it is unlikely to the point of practical impossibility that the Federal Circuit’s upcoming ruling in Myriad will be the last word in the case. Whatever result the court reaches is virtually certain to be appealed and, as we wrote earlier this year, there is little reason to expect that the judicial system will finally resolve the issue of gene patenting in 2011.

What Caught Our Ear in Myriad. The limited predictive value of this week’s oral argument has not stopped media and legal commentators from dissecting how the Federal Circuit is likely to rule. While there is no way to confidently predict how the Federal Circuit will rule when it issues its opinion, likely in the next 2-3 months, here are a few of the issues raised during oral argument that caught our ear:

Procedural Arguments. The court spent considerable time addressing two procedural arguments raised by Myriad (and the other defendant-appellants): (1) that the plaintiffs in the case lack standing to maintain the lawsuit (a very technical question focused on whether these plaintiffs face enough of an immediate threat from Myriad’s patents to be allowed to challenge them) and (2) that, even if the plaintiffs were to win on all of their claims, they would not get the practical outcome they want (opening up BRCA testing beyond Myriad’s monopoly) because they failed to challenge all of the Myriad patents and claims that apply to BRCA testing (redressability, in legal jargon).

Those arguments seemed to receive more attention in court than they did in the parties’ briefs. On the one hand, this may reflect nothing more than the fact that these issues come logically first – if a plaintiff lacks standing to sue a court is barred from considering that plaintiff’s substantive claims – and there was a limited amount of time available for oral argument.

Then again, the extensive procedural discussion certainly raises the possibility that the Federal Circuit might dispose of Myriad on technical procedural grounds. This view finds some support in the concerns voiced from the bench (particularly by Judge Moore) that a ruling in Myriad could have “dramatic” consequences for the biotechnology industry, and that the substantive issues surrounding the patentability of human genes might be more appropriately addressed by Congress.

A procedural ruling, however, would fail to address an issue (the patentability of genes) that has sown uncertainty throughout the industry and created a rift within the United States government.

It would also be every bit as likely to be appealed as a substantive ruling and, in the long run, would probably accomplish nothing more than delaying the inevitable. Even if Myriad is ultimately dismissed on procedural grounds, it seems highly likely that one or more of the current plaintiffs and/or Myriad’s potential commercial competitors will continue to press the issue.

Still, because Myriad is the current patent holder and dominant BRCA testing provider, a scenario in which the Federal Circuit dealt with Myriad on procedural grounds, and thereby further delayed a substantive resolution, would likely be a practical victory for Myriad.

Whole-Genome Sequencing. As soon as the discussion shifted from procedural to substantive matters, Judge Bryson posed a pointed question to Gregory Castanias, Myriad’s attorney:

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

The uncertain relationship between existing gene patents and emerging whole-genome sequencing technologies and services is one we first discussed nearly two years ago, and one that has been hovering at the periphery of the Myriad litigation.

On Monday Castanias struggled to answer the question directly, noting (correctly) that it would depend in part on whether the particular method of sequencing involved “using” an isolated DNA sequence covered by Myriad’s patents.

The issue was raised directly only one other time, by Christopher Hansen of the ACLU (arguing on behalf of the plaintiff-appellees) in the context of Myriad’s BRCA method claims. Those claims involve comparing or analyzing gene sequences to identify the presence of mutations corresponding to a predisposition to breast or ovarian cancer. According to Hansen, if the judges were to compare the wild-type BRCA sequence against the publicly available genome sequence from Personal Genome Project founder George Church, side-by-side on a computer screen, they would infringe Myriad’s patents.

As we move rapidly into an age where whole-genome sequence data is inexpensive and ubiquitous, and the process of genomic interpretation is increasingly separate from genomic data generation, Hansen’s example illustrates why the disposition of Myriad’s method claims may well be more important in the long run than whether isolated DNA sequences are held to be patentable. (Myriad’s method claims, incidentally, received fairly minimal treatment during oral argument, although this may simply be due to the issue appearing last in the briefs and thus coming up last in each party’s argument, when there was little time left.)

While none of the judges responded to Hansen’s hypothetical (likely due in large part to the fact that Hansen had run over his allotted time by that point), it is encouraging to see, particularly in Bryson’s earlier comment, that the court clearly recognizes the potential for conflict between gene patents and the new generation of personalized medicine products built upon whole-genome sequencing.

However, whether the Federal Circuit will address that issue when it rules on Myriad, as with every other issue, is anybody’s guess.

Composition of Matter and Gene Patents. Predictably, the most attention was devoted to the patentability under § 101 of isolated DNA sequences. Numerous hypothetical scenarios were offered up by each of the parties, and by the judges as well: diamond mines, baseball bats in trees and even a hypothetical “magical microscope” envisioned by Neal Kumar Katyal, arguing on behalf of the Department of Justice.

One concept to which the court (and particularly Judge Lourie) returned repeatedly during the course of the argument was covalent bonding. Judge Lourie focused on the importance of covalent bonds in the DNA molecule, noting that those bonds must be broken in order to isolate sections of the molecule for purposes of examination, and suggesting that breaking those bonds renders isolated DNA different from DNA in the human body.

The focus on covalent bonds may be an effort by the court, and particularly Lourie, to find a way to apply the teaching of more than a century of cases that seem to say that patentable compositions of matter must be different in kind from their natural precursors or variants. Judge Lourie (a chemist) was playing around with the breaking of the covalent bonds during “isolation” as a potential Rubicon, beyond which isolated genes might be different in kind from those in the body.

However, Lourie’s covalent bond test was not the only one proffered. The government, for its part, offered up its own “magic microscope” test. The magic microscope (a term Judge Moore found “kitschy”) would enable the direct observation of naturally occurring DNA. According to the government’s test, any DNA sequence visible through this hypothetical device (which, if DARPA has its way, might not remain hypothetical forever) would be unpatentable. On the other hand, all other molecules (including, e.g., cDNA) not occurring in precisely the same form in nature – and thus not visible through the microscope – would be patentable.

While we wait to see whether any of the tests or hypotheticals outlined in the oral argument emerge in the written Myriad opinion, the bottom line is that the court, assuming it reaches the merits of patentable subject matter, must (1) decide what different in kind means in the genetic context and (2) apply that test to “isolation,” as the Myriad patents define that term.

The Next Myriad Mile Marker. For those who are interested in diving deeper, the Federal Circuit has made an audio transcript of the hearing available on its website (mp3). For everyone else, the next significant development in the Myriad litigation will most likely be the Federal Circuit’s opinion, which should be handed down sometime in the next few months.

At that point the parties and amici will have something concrete to digest – and likely appeal – and, depending on the outcome, Myriad, its would-be competitors and clinicians, researchers and patients with an interest in BRCA testing may be put to some difficult practical decisions. Until then, however, let the waiting – and speculation – continue

This is also a good time to introduce Genomics Law Report readers to Sharon Goswami, the Genomics Law Report’s new intern. Sharon is a 2L at New York University’s School of Law and and holds a degree in chemical engineering from Princeton University. At NYU, she is technology co-chair of the student intellectual property organization IPELS and an active student member of the William C. Conner IP Inn of Court.

This edition of the Twitter Roundup is divided into two sections.

The FDA Meets DTC. Again. Since this is the first Twitter Roundup since the FDA’s two-day public panel meeting on direct-to-consumer (DTC) genetic testing two weeks ago, we have collected all of the recent tweets on that topic in a separate section. We covered this topic in extensive detail (see posts here, here and here), but there have been plenty of others sharing their thoughts and opinions on the meeting, the FDA’s actions and the future direction of DTC genetic testing. You can find links to many of those below, as well as Dan’s live-tweeting of the meeting itself. You can also find additional coverage on Twitter under the hashtag #FDADTC and you can find all of the GLR’s DTC coverage here.

Also in the News: Public Genomics and Patent Reform. All other Tweets are collected below as usual. In addition, here are a few recent highlights our readers may have missed.

Genetic Data in the Public Domain: Genomes Unzipped Implements CC0. Raw genetic data from the Genomes Unzipped (GNZ) contributors (including Dan) are now officially available under the Creative Commons CC0 public domain option. By placing data under CC0 the GNZ contributors have waived their copyright to their genetic information, permitting the use of those data without restriction or attribution. GNZ joins other efforts – including the Personal Genome Project (which also utilizes CC0), SNPedia and Sage Bionetworks – in seeking to broaden the availability of public genomic data.

GNZ data can be browsed using the group’s Genome Browser in a manner similar to the tools available through the International HapMap Project website – looking at particular sets of data that correspond to RefSeq materials. However, unlike the HapMap data, GNZ data comes from identified individuals who have chosen to share their genomic data with the public freely and without restriction.

Update on Patent Reform Legislation. Earlier this month, the Senate passed by a 95-5 vote the America Invents Act (S.23) or, as it is more commonly known, the Patent Reform Act of 2011 (pdf). Its passage, after six years of ongoing legislative debate, was hailed by many. President Barack Obama called it “the most significant patent reform in over half a century” and David Kappos, Director of the United States Patent and Trademark Office (PTO), declared it “a win for all American innovators, of all sizes and industries.”

Among the legislation’s numerous reform proposals, the most controversial is a proposed change to a first-to-file system (from a first-to-invent system), which would award priority in most cases to the first inventor to file with the PTO. Supporters of the switch to first-to-file, including the Biotechnology Industry Organization (BIO), argue that the change would bring the United States in line with international patent practice and that, on the whole, the reform would improve the U.S. patent system, spur innovation and create jobs.

Detractors, on the other hand, argue that the current first-to-invent system protects small inventors who lack the patent prosecution of large corporations. For example, the National Venture Capital Association (NVCA), the nation’s largest trade group for early-stage investors, argued this week that the current version of the Patent Reform Act substantially disadvantages small start-up companies and could harm innovation and investment.

Over the past few weeks, as politicians, lobbyists and industry groups have lined up on both sides of the Patent Reform Act, the bill’s odds of becoming law have become far less clear than they initially appeared. With the reform act currently stalled in the House (another hearing is set for next week) it remains to be seen whether 2011 will be the year that patent reform legislation is finally passed and, if so, what portions of the Senate version will survive the legislative process intact.

Now, on to the Tweets:

Tweets from or about the FDA’s public meeting on clinical DTC genetic testing:

• HT to @razibkhan & his post on “Genetic Paternalism & the FDA” http://bit.ly/hkJak9 for pointing me to Kari/deCODE quote #FDADTC
• GLR Post: Closer Scrutiny Ahead for DTC Genetic Testing Claims: http://bit.ly/gxnpEn #FDADTC
• Last wk’s House jobs forum reminder some in DC see #FDADTC regulation as inhibiting job creation: http://bit.ly/fjLXwJ cc @PathwayGenomics
• FDA promises reg guidance for mHealth apps this yr. @mobilehealth says it’s been happening for yrs: http://bit.ly/hiB9O2 sounds like #FDADTC
• RT @shwu: FDA’s summary of the #FDADTC panel meeting: http://1.usa.gov/hy6MPx
• Want to share your #FDADTC thoughts? CDRH Town Hall-Orlando-on 5/5: http://1.usa.gov/i2oGgp Shuren to discuss FDA strategic priorities
• RT @dgmacarthur: A more optimistic take on the #FDADTC meeting from @PathwayGenomics: http://cot.ag/gqGm1Z
• More excellent coverage from #FDADTC by Turna Ray of @pgx_reporter: http://bit.ly/fhiZ1U (sub)
• GLR Post: The FDA and DTC Genetic Testing: Setting the Record Straight: http://bit.ly/f9lWgq #FDADTC
• Have been told House DTC investigation “bipartisan,” not over simply due to Republican control of comm. Will E&C revisit GAO report? @shwu
• RT @shwu: Source docs for GAO restructuring: http://1.usa.gov/hPIzbt
• RT @dgmacarthur: Official who led GAO report into DTC genomics shown to have fudged schools report: http://bit.ly/eYyqZj (via @shwu)
• Expanded, revised #FDADTC slides for AM talk @DukeIGSP. Have posted for those interested: http://bit.ly/gRZ8mQ
• Different take on #FDADTC: RT @GW_The_Sample: Clinical Labs Should Rejoice Over FDA Panel’s DTC Genetic-Test Ruling: http://bit.ly/hewnDH
• DNA Dilemma: Denoument (or what @mary_carmichael would have liked to say to the #FDADTC panel): http://bit.ly/h6ckBe
• RT @genomesunzipped People have a fundamental right to access their own genetic information – a consensus statement: http://bit.ly/eQw8ai
• +1 RT @matthewmarkus: I enjoy analyzing lats & lons more than SNPs because my results don’t have to be routed through a geographer. #FDADTC
• RT @mary_carmichael: “PPl should be free to make own choices. Harm from [DTC] tests ltd, as is benefit.” Altshuler: http://bo.st/ffebu1
• RT @dgmacarthur: At @genomesunzipped, Joe Pickrell points out the benefits to research of DTC genetic testing: http://bit.ly/iecbZt #FDADTC
• Frustration with #FDADTC spilling from twitter to blogs (#2): @razibkhan prepares to defend his genomic rights: http://bit.ly/fIc7gl
• Frustration with #FDADTC spilling from twitter to blogs (#1): @DNAlawyer challenges FDA’s authority: http://bit.ly/fCinuI
• Detailed coverage from Day 1 of #FDADTC from @pgx_reporter: http://bit.ly/gyJimX (subscription)
• Need to think beyond spit kits, too. Where will WGS analysis occur? RT @MishaAngrist: Suspect lot of saliva will be headed offshore. #FDADTC
• Speakers? Probably. Panel itself? No. RT @RDGene: Gutierrez: assures panel that provided speakers that were balanced #FDADTC
• Add’l VC funding since. RT @RDGene: Rose Romeo @23andMe: layoffs referred to yesterday due to recruitment of experienced personnel #FDADTC
• That begs a good q: is DTC test must be routed through clinician, must post-test follow-up-eg surveys-go through clinician as well? #FDADTC
• RT @RDGene: Pathway: move to HP only model has made collection of lifestyle data used in risk calcs more difficult #FDADTC
• Panel composition not well balanced. RT @shwu: All this concern for consumers-has anyone thought to ask consumers themselves? #FDADTC
• Assume from audience, not from panel/FDA. RT @RDGene: (Round of applause when Pendergrast finished her talk #FDADTC)
• RT @aliciaault: Pendergast said MDs on panel could not keep info from consumers, nor compel them to see MDs after test results. #FDADTC
• RT @aliciaault: Wow, former FDA official Mary Pendergast just chewed out the panel for being paternalistic, controlling doctors. #FDADTC
• Breaking for lunch at #FDADTC. That’s going to be it for me as off to @DukeIGSP: http://bit.ly/bkroGw. Will follow rest of mtg from afar.
• Mansfield: we have used direct-to-consumer for simplification. Tests also called “direct access,” various other terms. #FDADTC
• Mahowald: key idea is people are buying these tests. (Not sure I see consumer/customer distinction Mahowald is trying to make) #FDADTC
• Mahowald: wants to make a strong pitch to change from “consumer” to “customer”; wants panel to vote on it #FDADTC (What’s the difference?)
• Ng: need a pre-test/post-test risk calculator? Know in advance extent genetic info will modify your risk after consid other factors #FDADTC
• House: why can’t we tell individuals that the test has limitations (not all factors incl), but allow them to manage that information #FDADTC
• House: assume we have approved genetic test mtg FDA reg requirements. If that test is not the only factor, why not make avail #FDADTC
• Hersch: issue imp for labeling; clarify medical risk uncertain, true risk of disease must be considered in context of other factors #FDADTC
• D’Agostino: tests should be developed in light of existing knowledge, incl. all relevant clinical parameters (not just genetic) #FDADTC
• Netto: inability of DTC companies to provide other types of data collection, interpretation is what will keep most tests from DTC #FDADTC
• Netto: this is the issue that is going to bring most DTC back to prescription testing; to do this properly will need a clinician #FDADTC
• Ransohoff: patient is not really interested in “what’s my test result”? Interested in “what’s my risk for X”? (Do consumers agree?) #FDADTC
• D’Agostino: absolutely. Ransohoff: a great q b/c it shows distinction b/w HIV test and a genetic test – latter has add’l complexity #FDADTC
• Q from FDA to panel: should test reports for future risks incl. warnings/info about add’l risk factors (eg env, health history) #FDADTC
• Lipkin and others generally agree that absolute risk is easiest for consumers to understand; can have relative risk as well #FDADTC
• Lee: descriptive categories easiest to understand (for consumers), but need to be tied to number (absolute risk) #FDADTC
• Q from FDA to panel: what are best ways to present risk to consumers in genetic testing context? Relative, absolute, high/low risk #FDADTC
• Lipkin: need to make avail genetic “counseling” by a qualified individual; whether that’s a GC or somebody else TBD #FDADTC
• Tsongalis: are we confusing genetic counseling w/ clinical counseling? GC’s and MD’s have different roles #FDADTC
• Ransohoff: making GC available may not be enough. Disingenuous to leave too much in hands of consumer. #FDADTC
• (NB: panel discussion at this point is all hypothetical; background assumption is their rec to FDA that most/all tests not DTC #FDADTC)
• Wyne: if we let tests go DTC w/out “routing through clinician,” should at least make a GC available #FDADTC
• Wyne: should rec involvement of GC; the fact #s are insufficient today is not a surprise; field is growing, more GCs will be trained #FDADTC
• Ransohoff: if a test is so complicated that a genetic counselor is required, then perhaps that is a sign the test shouldn’t be DTC #FDADTC
• Shamburek: sub-specialists are nice for specific traits (HD), but won’t work for whole-exome, WGS; need broader genetics expertise #FDADTC
• FDA: looking for recommendation from panel: should GCs be required, should they be available? How should they be involved? #FDADTC
• Gallagher: agrees, but notes not enough qualified genetic counselors; also be wary of conflict of interest (GCs employed by co) #FDADTC
• Mahowald: important that the clinician involved in genetic testing counseling be “qualified”; cos obligated to ensure this. #FDADTC
• Panel now asked to consider appropriate role of genetic counselors in clinical DTC genetic testing #FDADTC HT @GenCounsNews @alliejanson
• Gutierrez: but given panel is clear that most (maybe all?) tests should not be DTC, ok to move on #FDADTC
• Gutierrez: when we put panel together, had to consider possibility of panel going either pro or con on DTC. So qs thus designed #FDADTC
• (Panel clarifying that high-risk tests should not be available DTC; but panel reminded – by other panelists – that only making recs #FDADTC)
• Wyne: how do you decide what is medically actionable w/ 100,000 genes on chip? Screen every one? #FDADTC
• Gutierrez: consider whether particular disease/ symptom requires clinical intervention – requirement of going through MD #FDADTC
• Wyne: can we allow as DTC anything that is not “medically actionable”? #FDADTC
• Panel: will we be asked about privacy issues related to (DTC) genetic testing? Mansfield: not the place for that discussion either #FDADTC
• Hirschhorn: how will FDA integrate regulation w/ state laws? Gutierrez: not the place for this discussion. #FDADTC
• Shamburek: much of practice of medicine is “routed through physician”; genetic testing can follow same pathway for certain tests #FDADTC
• Netto: needs to be sure consumers are told that a test, delivered to clinician, will wind up in medical record #FDADTC
• Panel now discussing whether people test DTC b/c they are trying to avoid putting information in medical record #FDADTC
• (Interesting panel so reluctant to limit access of test to targeted pop’n-want wide access-but not concerned w/ limiting in toto #FDADTC)
• Panel seems to agree: can regulate test, marketing claims – but once test out there should be available to everyone #FDADTC
• Panel: going to be hard to define which pop’n is target? how would FDA be able to control/limit avail of testing? #FDADTC
• Q from FDA: Should test for rare conditions/marker be offered only to pop’n with higher prevalence of condition/marker? #FDADTC
• Shambuurek: suggests NIH genetic testing registry as place to provide info for confirmatory testing, follow up info for patients/MDs #FDADTC
• Panel qs: will consumer have option to order competitor’s test to confirm? How will this happen? Will result in unnecessary testing? #FDADTC
• Ransohoff: in general, confirmatory testing imp. But FDA needs to tie to the clinical significance, risk of the test-case-by-case #FDADTC
• Panelists: confirmatory testing very important; responsibility should be on cos to provide confirmatory testing #FDADTC
• (Prediction: panel will favor confirmatory testing #FDADTC)
• Q from FDA to panel: how to address false positive rate in rare disease pop’n? Should there be confirmatory testing in this situ? #FDADTC
• Question from FDA to panel: “what are essential risk mitigation tools to providing DTC genetic tests?” #FDADTC
• (The panel keeps coming back to “how do we know these tests actually work?” FDA keeps saying – we’re going to regulate like devices #FDADTC)
• Gutierrez: accuracy/validity of test will be regulated by FDA. For high-risk (Class I) will be on cos to prove safety, efficacy #FDADTC
• (Unfortunate that panel didn’t take up House’s suggestion to use consumer-demonstrated education as a form of mitigation #FDADTC)
• Gutierrez: clarifies re: labeling. For FDA “labeling” means everything, including advertising #FDADTC
• Ransohoff: will FDA judge the genetic test “package” or each individual test w/in that package/test panel #FDADTC
• Ransohoff: heard good exs of mitigation from Benson’s (FDA) talk this AM. But FDA needs to consider every single SNP/claim on panel #FDADTC
• (House w/ a really interesting suggestion. Similar to what PGP requires in the form of an entrance exam http://bit.ly/i8NOV3 #FDADTC)
• House: can FDA req patient to pass some type of screening/educational exam prior to ordering a test DTC to address info concerns? #FDADTC
• Hejazi: what about Humanitarian Device Exemption route for DTC? Gutierrez: doesn’t think cos limiting to small enough pop’n #FDADTC
• Waterson/Mansfield: here we’re talking about hypothetical. If FDA *does* permit some tests DTC, what mitigation measures req? #FDADTC
• D’Agostino: clarifying that yesterday we recommended most tests should *not* be DTC. Did this change? #FDADTC
• Shamburek: addition to pre-test info, labeling, will need to be confirmatory testing in many cases. That risk/cost must be shared #FDADTC
• Boughman: will depend heavily on FDA to evaluate proprietary algorithms. Davis: labeling needs to be appropriately simple #FDADTC
• Q to panel: when might info to consumers about risks/benefits be sufficient to allow for DTC genetic testing? #FDADTC
• Panel in general agreement re: need for truth in labeling/advertising for genetic tests – necessary but not sufficient for DTC path #FDADTC
• For #FDADTC, clarified during break: FDA appears to be leaning toward DTC as home use kit (for DNA collection) + med device (for claims)
• Shamburek: if truth in labeling, consumers can understand some tests / FDA can work w/ FTC to ensure this #FDADTC
• Panel now considering second of charged questions: http://bit.ly/hvOR9Z Basically: what mitigations avail for DTC tests #FDADTC
• Netto: another issue: DTC means results don’t necessarily wind up in medical record. (True but may be a reason some desire DTC) #FDADTC
• (Very difficult to see how that model doesn’t bankrupt both FDA & any test sponsor. However, know FDA is looking at alternatives #FDADTC)
• (Heard FDA – I think Philip – confirm that each new variant, claim needs to be submitted, validated, approved separately. #FDADTC)
• (This followed by minimal discussion of how to deal w/ adding new variants, claims to massively multiplex/WGS testing #FDADTC)
• Netto: Very difficult to separate these two. Ultimately, have to look at each test independently. #FDADTC
• Netto: clarifying, again, that genetic tests *will* be regulated. Issue whether MDs involved in order/interp. #FDADTC
• Ransohoff: is idea that if risk isn’t great, DTC bar gets lowered? Gutierrez: yes, but still concerned w/ truth & accuracy of claims #FDADTC
• Gutierrez: this is q for today. What are DTC test sponsor’s responsibilities? How can FDA mitigate risk & help ppl understand test? #FDADTC
• Ransohoff how will genetic test complexity be digested by cos/FDA before reaching indiv? If MDs can’t understand, is anything DTC? #FDADTC
• (This is the akin to the notion of personal utility that the panel seemed not-so-interested in when discussing DTC yesterday. #FDADTC)
• Panelist (Hersch): future risk can be clinically significant b/c it makes people to make all kinds of decisions about what they do. #FDADTC
• Philip: some of those claims could be prevention claims – which would be clinically significant. #FDADTC
• Mahowald: how is a test clinically significant when somebody could not become symptomatic for decades? (Or is already symptomatic?) #FDADTC
• Philip: even in asymptomatic pop’n, need to lay out intended use. FDA looks at if in target pop’n test will give clin. sig. res. #FDADTC
• Mahowald: What constitutes clinical use? For long-term risk assessment, w/ clinical application long in future, is that clinical? #FDADTC
• Panelist (Mahowald): still trying to get a handle on intended use. Intended use refers to clinical indication? #FDADTC
• Philip: We’ll look @ analytical validation for future tech (incl. WGS), but need input re: validation (analytical/clinical) of tests #FDADTC
• FDA (Philip): we know WGS is at the door; have started looking at validating this technology. E.g. have cleared 60 mutations for CF. #FDADTC
• Panelist (Tsongalis): how will you move from SNP/single-trait testing to massive multiplexing, whole-genome sequencing? #FDADTC
• Gutierrez: In end, we will make public our reviews, incl. bases we found something sub equivalent (510(k) and/or safe & effective. #FDADTC
• Gutierrez: cos will offer reg submissions; FDA will work w/ cos to shape those. Point of mtg, to help FDA do this #FDADTC
• Gutierrez: FDA on record of saying that DTC genetic testing should be regulated. Talking w/ cos about how to comply #FDADTC
• (A bunch of back-and-forth between panel and FDA – particularly Gutierrez. Will try to summarize for #FDADTC)
• Seems likely for non-clinical, incl. n-c DTC RT @RDGene: Gutierrez states that some low risk genetic tests may be considered Class 1 #FDADTC
• Gutierrez: considering how to down-regulate where possible ;have considered panels to help set correct reg (in context of LDTs) #FDADTC
• Gutierrez: FDA regulates based on risk. Depends on intended use; try to not make extra work for ourselves, get to appropriate risk #FDADTC
• Panel q from Hejazi (industry rep): asking how agency intends to regulate genetic tests? #FDADTC
• Gutierrez: part of FDA’s mission, since 1976, to regulate all in vitro diagnostics for safety, efficacy. Genetic tests included. #FDADTC
• Panel q: what prompted FDA to start regulating prescription genetic tests (IVD tests)? #FDADTC
• (Job got in the way of #FDADTC this morning. Back in the room now & catching up thanks to tweets from @aliciaault and @RDGene)
• GLR Post: Looking Ahead After the FDA’s DTC Meeting: http://bit.ly/hiK5te #FDADTC
• After very long day at #FDADTC, here are my 1st thoughts: http://bit.ly/hiK5te Take-away for DTC proponents: don’t panic.
• Quick & on point RT @dgmacarthur: My attempt to piece together the early events from day one of the #FDADTC meeting: http://bit.ly/fVNcsy
• RT @MishaAngrist: “Making movies” My take on the FDA-23andMe-Congressional Hearings contretemps. http://bit.ly/dOyi22 #FDADTC
• That’s the close of the #FDADTC discussion for today. Panelists reminded once against not to discuss subject matter of mtg outside of panel
• Query: is personal utility (i.e., satisfaction) other side of anxiety? If anxiety considered shouldn’t personal utility be as well? #FDADTC
• Boughman: avoid paternalism: distinguish between data showing anxiety vs. anticipation of anxiety #FDADTC
• Lipkin: data on anxiety doesn’t meet criteria for clinical significance Waterson: but tests weren’t for serious traits like BRCA #FDADTC
• Next q for panel: should anxiety be considered in assessment of safety and effectiveness? #FDADTC
• Waterson: “sense I’m getting from committee” is to not include personal utility in considering clinical significance #FDADTC
• Ransohoff: personal utility is important, but also very susceptible to marketing manipulation. #FDADTC
• FDA clarifying for panel statutory definition of clinical significance. Netto: on that definition, no evid of clinical sig for DTC #FDADTC
• (Waterson: does FDA have statutory authority to consider personal utility? Mansfield: “assume that we do.” #FDADTC)
• Next panel question: should personal utility be incorporated in considerations of “clinically significant results”? #FDADTC
• Important clarification from panel: is “physician” the individual’s physician, or a company physician? #FDADTC
• House is consistent voice of disagreement; thinks patients sophisticated enough to understand when clinical consult needed #FDADTC
• (Most panelists seem to think that, regardless of DTC ordering, results should be returned through physician #FDADTC)
• Ng: any result w/ a high predictor a person will develop a disease, w/ clinical utility, needs to be funneled through physician #FDADTC
• Mansfield: “routing through physician” means report results to physician *only*; MD decides whether/how to pass to patient #FDADTC
• (Waterson offers that ordering must be by provder; two panelists quickly disagree – if reviewed by provider then ordering DTC OK #FDADTC)
• Next question for panel: are there tests that can be ordered DTC as long as results are reviewed by clinician? #FDADTC
• Waterson: “I don’t know if I’m getting a clear sense” on nutrigenetic testing. Concerns around testing claims, not test themselves #FDADTC
• Mansfield: clarifies again that for all tests FDA intends to regulate to ensure analytical/clinical validity. Q is avail of DTC path #FDADTC
• Panel is treating “nutrigenetic” as a bit of a catch-all category for testing that seems “health-related,” but maybe not clinical #FDADTC
• Shamburek: thinks generally low risk, but still concerned about underlying analytical/clinical validity of nutrigenetic tests #FDADTC
• Nutrigenetic discussion turning to MTHFR-folate testing, recommendations. #FDADTC (panel jumping around quite a bit right now)
• Final part of question #1: what about nutrigenetic tests? Should those be available DTC w/out clinician guidance? #FDADTC
• Continue to think Waterson (#FDADTC panel chair) oversimplifying range of views, opinions raised by panel. To be fair he has impossible task
• Waterson: “getting the panel’s sense again that [PGx] should, for time being, be under MD/provider purview” #FDADTC
• Boughman: asks for clarification from FDA re: labeling for PGx tests. Mansfield: most PGx tests described not req (but see Abacavir) #FDADTC
• Panelist: aren’t there Hep-c, HIV tests offered DTC? Mansfield: over-the-counter, not DTC. (Promises to clarify distinction tom.) #FDADTC
• Next category: PGx testing. Does risk of offering PGx tests DTC outweigh the benefits? #FDADTC
• Mansfield: we’re looking for weight of risks/benefits of DTC channel, not whether the tests are safe. #FDADTC
• Hejazi: if we req genetic testing through physician, what about ppl who do not have a physician/hc coverage? How do they get data? #FDADTC
• Mansfield: we cannot consider cost of test in determining regulation. Panel: cost as means of data avail still part of pro/con #FDADTC
• Tiffany House (patient rep): can’t wait to have all of the answers, b/c we will never have all of the answers #FDADTC
• RT @DNAlawyer: FYI Shuren’s testimony in July said FDA focuses on tests “intended for use” http://1.usa.gov/dSXqfQ not possible medical use
• (And a helpful clarification from Mansfield: what matters is *intended* use, not clinical significance. #FDADTC)
• (What’s not clear from FDA: is it *possible* clinical use or *intended* clinical use that labels a test “clinical” for #FDADTC purposes?)
• Panelist rightly challenges Mansfield. You cannot necessary separate out clinical from non-clinical. #FDADTC
• Mansfield: clarifying what FDA does / does not consider clinical DTC tests (FDA not interested in non-clinical tests) #FDADTC
• (Boughman’s arg seemed to be data is too complex for DTC delivery. Interested consumers should work through trad’l HC channels #FDADTC)
• Joann Boughman, ASHG: do consumers have “right to know”? Not ready for DTC. Motivated ppl can advocate through traditional HC system #FDADTC
• Panel now considering DTC w/out clinical involvement for susceptibility testing (FDA’s ex: APOE/Alzheimer’s) #FDADTC
• (Waterson has twice declared “consensus” despite disagreement from other panelists, as well as less than half the panel weighing in #FDADTC)
• Waterson (chair): again declares consensus on pre-symptomatic testing-through docs, not DTC. #FDADTC
• (One theory: #FDADTC panel gravitating twd Huntington’s b/c monogenic, bright-line disease/test? Easier to analyze, ‘tho not good DTC model)
• Panel does seem in agreement that Huntington’s testing shouldn’t be DTC (Curious if this is even avail DTC? Anyone know?) #FDADTC
• Mary Mahowald arguing that some pre-symptomatic testing (incl. BRCA) could be offered DTC, in some circumstances #FDADTC
• (Exs FDA provided for panel to consider for pre-symptomatic testing category: BRCA, Huntington’s #FDADTC)
• Not sure we reached any consensus, but moving on: value of offering pre-symptomatic genetic testing DTC w/out clinician involved #FDADTC
• (A critical point, added as a clarification, from Gutierrez. No “enforcement discretion” for genetic testing. Issue is avail of DTC #FDADTC)
• Gutierrez: clarifies that whether FDA will regulate companies is *not* on table. Issue is whether the DTC pathway will remain open #FDADTC
• Several panelists object to “consensus”. Led by Tiffany House, panel’s lone patient rep. Concerned some MDs won’t prescribe tests. #FDADTC
• Waterson (chair) concludes there is a consensus that carrier testing should not be DTC for now. #FDADTC
• (Get sense panelists are feeling rushed, pressured to make recommendation on very complex area/very quickly. AG trying to reassure #FDADTC)
• Alberto Gutierrez, OIVD: what FDA looking for is general concepts; is it possible to move ahead w/ DTC in these categories or not? #FDADTC
• Panelist: 5-10 years before able to make definitive determinations; caution first, then make recommendations much later #FDADTC
• Several panelists: even w/in category of carrier testing, must go through each test one-by-one & make DTC determination-No shortcuts #FDADTC
• First comments from panels industry rep, Shahram Hejazi (http://bit.ly/dGXLcp) – focus on clinical validity #FDADTC
• (Last tweet was confusing: the panel is 22 ppl. Going to be tough to build consensus from such a large group. But good discussion #FDADTC)
• Not surprisingly, appears to be no clear consensus from the panel on appropriateness of DTC carrier testing (of nearly 2 dozen ppl) #FDADTC
• Tiffany House (patient rep on panel; Int’l Pompe Association) supports DTC availability provided there is full, complete disclosure #FDADTC
• Panel discussion fairly wide-ranging; panel chair (John Waterson, Children’s Hospital Oakland) doing a good job trying to focus #FDADTC
• Panel to consider each question in context of 1) carrier, 2) pre-symptomatic, 3) susceptibility, 4) PGx & 5) nutrigenetic testing #FDADTC
• First #FDADTC question is, essentially, what are risks/benefits of offering different types of DTC genetic tests w/out clinician involvement
• #FDADTC resumes. The panel is now going to be discussing the first of two charged questions (see: http://1.usa.gov/hvZmc9)
• Good panel q moving us away from discussion about how to interpret genetic information to where consumers belong in the picture #FDADTC
• Gulcher: GWAS is essentially over; we’re now into WGS. (Notes decode sequencing Icelandic population-2,500 WGS, imputation of rest) #FDADTC
• Back-and-forth re: DTC genetic testing & risk prediction w/out family history, etc. Gulcher: add’l info valuable; panel skeptical #FDADTC
• Gulcher of deCode response: DTC genetic test not a substitute for traditional clinical guidance; a supplemental service #FDADTC
• Response to panel q, JG of CRG criticizing DTC companies for only providing “part of the whole”; genetic data, but not FH, env data #FDADTC
• Unfortunately, no. Public mtg not as public as it might be. RT @bigs: .@genomicslawyer is there a video feed for #FDADTC?
• panelist q: any lawsuits against @23andMe claiming damage? Gould: no, none. #FDADTC
• Q re: non-paternity disclosure through DTC testing. AG: that’s part of the risks we disclose in consent to test process #FDADTC
• AG: thinks DTC well positioned to collect long-term outcomes data; outcomes data reporting a good form of oversight #FDADTC
• Panelist offering two anecdotes of patients who came with @23andMe data; one positive outcome, one misinterpretation. #FDADTC
• True, generally. But clinical blurs that line RT @DNAlawyer: In commerce setting, the q is capacity to consent, not informed consent #FDADTC
• AG of @23andMe: genetic testing can be used to confirm/contradict family history; also many customers who are adopted & have no FH #FDADTC
• Panel: “the cheapest genetic test is a good family history”; how does this compare to DTC genetic testing #FDADTC
• (These are important questions; clear need for stronger identity verification mechanisms in DTC genetic testing #FDADTC)
• Panel now asking about DTC genetic testing of minors, disabled adults – others who cannot provide informed consent. #FDADTC
• (For background, here’s the recent GLR post on this issue – surreptitious genetic testing: http://bit.ly/eAncsm #FDADTC)
• Panel q: how can we be sure that DNA being tested was provided by person purchasing the test? Challenge of identity verification. #FDADTC
• Panel distinguishing b/w studies testing for anxiety due to DTC (we have some) & long-term outcome DTC studies (we have none) #FDADTC
• Panel grilling Gulcher of deCode re: whether DTC results in harms. Gulcher agrees we need more long-term data, but no harms so far. #FDADTC
• AG: data owned by consumer; can be downloaded directly “Your data is your data” @23andMe also conducts opt-in research, internal R&D #FDADTC
• #FDADTC panelists now have opportunity to question the last group of speakers. First q, to AG: where does DTC data go & who owns it? #FDADTC
• AM: arguing for increase in funding, genetic testing training for nurses. (Another good point, but not sure FDA’s decision) #FDADTC
• AM: concerned about CLIA’s lack of PT for genetic testing, different pathways for IVD kits, LDTs (imp points, but more #FDALDT than #FDADTC)
• AM: focus on 1) role of nurses (largest HC gropu) in genetic testing, 2) who should order & 3) ANA perspective on DTC model #FDADTC
• Now up, Ann Maradiegue, George Mason (http://bit.ly/hpA5kY), presenting on behalf of American Nurses Association #FDADTC
• DK: major limitations of the study – no longitudinal data; pressing need to collect more / longitudinal / outcomes data #FDADTC
• DK now providing more detail re: how GPPC evaluated DTC misunderstanding. 4% confused about high-risk, 7% confused about low-risk. #FDADTC
• DK: limitations of survey – single point-in-time, no follow-up; no data on specific tests, only aggregate data #FDADTC
• (Here’s a better link to the GPPC data presented at ASHG in 2010: http://bit.ly/hdoAK0 #FDADTC)
• Now up, David Kaufman, JHU Genetics & Public Policy Center. Discussing DTC survey results from 2010 ASHG mtg: http://bit.ly/eTofcV #FDADTC
• JG reading directly from CRG’s public record comments. You can find those here: http://bit.ly/dGvMH5 (so won’t live-tweet this one) #FDADTC
• Now up, Jeremy Gruber, Pres of Council for Responsible for Genetics #FDADTC
• LB: market forces will ultimately eliminate genetic tests that are not valuable; but (reasonable) oversight still needed #FDADTC
• (LB’s def of genetic test is a single indication/intended use. Result: many tests will be dozens->hundreds->thousands of tests #FDADTC)
• LB: high-risk tests should not be DTC; low- & moderate-risk tests should be registered w/ FDA & be conducted in a CLIA lab #FDADTC
• (LB outlining a proposal for DTC regulation that sounds very similar to risk-based approach FDA discussed for LDTs last summer #FDADTC)
• LB: FDA interested in protecting public health; arguing “empowering individuals to maintain good health is in the public interest” #FDADTC
• (Note Interleukin is one of a very few publicly traded companies offering clinical DTC genetic testing – possibly the only one? #FDADTC)
• Now up, Lewis Bender, CEO of Interleukin Genetics (co offers single-condition DTC tests) #FDADTC
• AG: “genetic information provided DTC should be held to the same standards as genetic information provided in a clinical setting.” #FDADTC
• AG: urging flexible, forward-looking policy & regulation. Proposing a working group for defining clinical validity #FDADTC
• AG: regulation needs to be based on data, not on unsubstantiated fears/concerns; also need to recognize benefits of DTC #FDADTC
• AG: we have >75K genotyped customers, and we have no evidence that there are real, demonstrable risks from DTC genetic testing #FDADTC
• AG: we believe people have a “fundamental right” to access their own DNA. That right incl accurate, reliable genetic information #FDADTC
• AG: we consider ourselves industry leaders w/ regard to transparency, but always room for improvement. Opp for better edu, clarity #FDADTC
• AG: we use definitions/disclaimers – we are clear about what we do/do not test for; highlighting info comm tools #FDADTC
• AG: highlight the likely transition from genotyping to whole-genome sequencing; will impact how we think of validity #FDADTC
• AG: reg framework for all genetic testing cos (not just DTC) need clear standards for analytical, clinical validity #FDADTC
• You can find AG/@23andMe slides here: ( http://bit.ly/dLnFzJ ) AG: working w/ FDA on regulation, believe we have a path to approval #FDADTC
• Now up, Ashley Gould, GC of @23andMe #FDADTC (for those not here, the public presentations are very short, rushed)
• JG sharing his personal encounter with genetic testing/healthcare. Information DTC, but actual treatment requires clinician #FDADTC
• Written public comments in favor of DTC: http://1.usa.gov/eB9gMe (Mary Pendergast), http://1.usa.gov/ffgVf7 (Kevin Davies) #FDATDTC HT @shwu
• #FDADTC resumes with public presentations. First is from Jeff Gulcher of @decodegenetics re: DTC genetics for common diseases
• Damn good question. RT @wimufi: FDA staff not supposed to discuss topic, among themselves or with public, during lunch … Why? #FDADTC
• (Taking a lunch break at #FDADTC. “Open public hearing” starts after lunch. See: http://1.usa.gov/evayRl)
• (On physicians and genetic testing, take a look at this from @pgx_reporter: http://bit.ly/eBaokC – although not necessarily DTC
• Q: what about studies examining response of physicians to genetic testing results, incl DTC? CB: not aware of anything specific #FDADTC
• Q: how was @Navigenics chosen as the test for the Scripps study? CB: @EricTopol approached major DTC companies, Navi was interested #FDADTC
• CB says findings are consistent w/ existing lit on impact of genetic testing (not just DTC). (That’s true, but very ltd data) #FDADTC
• Panel pressing CB on very short (3 mo) time between testing & follow-up. CB agrees it’s a very fair point #FDADTC
• CB: overall result of DTC genetic testing in the Scripps population? Not a large impact one way or the other #FDADTC
• CB: sharing test results w/ physician was associated w/ some changes (e.g., exercise); sharing w/ GCs did not. But needs follow up #FDADTC
• CB: sharing test results with healthcare providers? Only 10% sought (free) genetic counseling; >25% shared results w/ physician #FDADTC
• CB: changes in behavior as result of screening? plenty of intent to change, but not nearly as much actual change #FDADTC
• CB: showing data on anxiety levels resulting from testing for different sub-groups; general lack of increase in anxiety in cohort #FDADTC
• CB: 5,000 enrolled, 3,400 viewed results, just over half were avail for follow up #FDADTC
• CB: a second disclaimer, while showing @Navigenics screenshots, that Scripps did not evaluate the Navi product itself #FDADTC
• (CB describing use of Navigenics test in Scripps study; keep in mind that this was the test version circa 2008 #FDADTC)
• CB: also unlike Multiplex Initiative, Scripps study was not free to participants – prices ranged from ~$150-$500 #FDADTC
• CB: sample was limited, not selected from within known population (as was the case with Multiplex Initiative) #FDADTC
• CB: emphasizes that the study did not evaluate the Navigenics test that was used for SGHI (incl. clinical validity, etc. of test) #FDADTC
• CB: lack of data on consumer response to DTC; that’s where Scripps Genomic Health Initiative (SGHI) comes in http://1.usa.gov/fDJyoy #FDADTC
• CB: presenting data from the Scripps/NEJM DTC study. Starting with overview of “personal consumer genetics” #FDADTC
• Final speaker of the morning: Dr. Cinammon Bloss speaking about recent Scripps/NEJM (http://bit.ly/hUIuBi) HT @EricTopol
• CM: MI emphasized that genetics only part of the story; need to also have full family history, talk to healthcare provider #FDADTC
• CM: MI was free, used a limited set of markers/traits, all participants were insured. #FDADTC
• CM: BUT the Multiplex Initiative has several crucial differences from current commercial DTC genetic tests. #FDADTC
• CM: public *should* be able to understand limits of genetic testing. (We are obliged to give them info needed to understand) #FDADTC
• CM: recommendations from Multiplex Initiative for DTC? DTC “may be OK” if appropriate presentation of results, pros/cons & support #FDADTC
• CM: take home messages: 3) testers can understand the limits of tests, feedback following testing #FDADTC
• CM: take home messages: 1) lots of self-selection in pop’n 2) effective communication provides adequate support #FDADTC
• CM: not a high level of emotions resulting from participating, but where expressed they were general positive #FDADTC
• CM: w/ prompting, “virtually everyone” could describe whether or not they had a particular variant for a particular health condition #FDADTC
• CM: followed up with participants to evaluate their unprompted/prompted recall of pers results from MI – great idea #FDAMTC
• CM: low-education, male were traits that reduced participation in MI #FDADTC
• CM: taking pains to point out that MI was not a study of the “worried well”, though did have high understanding of genetics #FDADTC
• CM: detailed review of multiplex initiative study aims, designs #FDADTC (Background info here: http://1.usa.gov/hXOUzX)
• CM: involved oversampling of traditionally under-represented groups in genetic testing #FDADTC
• CM: Multiplex Initiated in light of arrival of DTC. Develop an ideal pop’n sample: eliminate barriers, ensure informed consent #FDADTC
• Now up: Colleen McBride, NHGRI, talking about Multiplex Initiative #FDADTC
• (I’m speaking next at #FDADTC so won’t be Tweeting – I can multi-task, but not quite that well. My slides are here: http://bit.ly/fcPUyI)
• NW ultimately making standard arg. for involvement of healthcare providers in DTC. But her exs, evidence leave much to be desired #FDADTC
• True. RT @aliciaault: Wexler did start out describing her biases on testing: family hist of HD & basic bias against industry. #FDADTC
• Panel member pressing NW on her paternalistic stance – denying individuals access to genetic information. #FDADTC
• NW: people don’t understand genetic testing; we need to pull back on all of this. No more “spit parties” #FDADTC (The rhetoric continues)
• (Respect NW’s contributions to science but cannot credit her understanding or analysis of where DTC is or what it’s motivations are #FDADTC)
• NW accuses DTC of “raping the human genome project” (did I possibly hear that correctly? can anyone confirm?) #FDADTC
• NW: DTC companies should be closed and DTC should be eliminated. DTC preys on our worst aspects, prey on snobbery & the rich #FDADTC
• (For ref: MyGeneProfile is a Singapore-based company & a pure scam. #FDADTC needs to address this, but hardly representative of industry)
• NW now moving on to GAO report on DTC genetic testing #FDADTC
• (Disappointed that NW drawing all of her conclusion about state, risks of DTC from MyGeneProfile #FDADTC)
• (My opinion: irresponsible of NW. Not a US company, not representative of DTC. Not even sure MyGeneProfile is an actual company. #FDADTC)
• NW is now showing MyGeneProfile (complete genetic scam, see @dgmacarthur: http://bit.ly/f58AYH) as representative of risks of DTC #FDADTC
• NW drawing direct line b/w exp. of friend w/ HD who committed suicide to DTC tests on shelves of Wal-Mart. I can’t make that jump #FDADTC
• NW speaking broadly about HD testing concerns. Share many, but agree w/ @lindaavey that not best model w/ which to debate #FDADTC oversight
• That doesn’t surprise me – I don’t know of any. RT @DNAlawyer: @genomicslawyer No huntington DTC test at of 5/2010: http://bit.ly/dSSAIf
• (Not aware of any providers offering testing for Huntington’s DTC. #FDADTC)
• NW: describing guidelines for Huntington’s Disease testing, including privacy & informed consent requirements. #FDADTC
• (RT @mary_carmichael: As #FDADTC gets hashed out, @virginiahughes takes a thoughtful tour of her @23andMe results: http://bit.ly/hqTwxM)
• NW focusing on Huntington’s disease gene discovery, a process in which she was instrumental. #FDADTC
• NW now describing her involvement in, history of the Hereditary Disease Foundation: http://bit.ly/gBF15R #FDADTC
• NW speaking personally, with own biases/fears. But believes those are shared by everyone with DNA. (Not sure I agree. At all.) #FDADTC
• Now up at #FDADTC, Dr. Nancy Wexler, Columbia: “Toxic Information: Handle With Care”
• (GLR post from 1 year ago, on why markers of DTC industry failure aren’t really: http://bit.ly/dtqTes Analysis hasn’t changed since #FDADTC)
• SH: thinks the fact we have no data is indicative of lack of enforcement – regulation improves data-gathering #FDADTC
• Q for SH: do we know anything about volume of cross-border activity for DTC genetic testing? SH: no. (I’d give same answer) #FDADTC
• Q for SH: why does UK have such a light touch on DTC? SH: historical (e.g., eugenics) & cultural factors are stronger elsewhere #FDADTC
• Questions from panel to SH focusing on appropriateness of clinical utility as a standard for DTC genetic testing regulation #FDADTC
• SH’s closing thought: “let’s try to avoid disaster” (although not clear what, exactly, the disaster to be averted is) #FDADTC
• (I disagree fairly strongly w/ SH on that point. @23andMe continues to raise money, deCodes bankruptcy not tied to DTC, etc. #FDADTC)
• SH: arguing DTC doesn’t work by pointing to Sciona struggles, @23andMe layoffs & @decodegenetics bankruptcy. #FDADTC
• SH: thinks enforcement will grow if DTC market grows, but SH skeptical that DTC will stick. Thinks business model entirely unproven #FDADTC
• SH’s conclusions: # of DTC companies, countries regulating DTC both increasing. But rulemaking, guidance does not equal enforcement #FDADTC
• SH: like SACGHS, HGC now being wound up. UK may be unique in world in diminishing its oversight of DTC over the past 15 years #FDADTC
• SH: key issue of divergence: tests need to be delivered w/ clinical supervision? (Agree: the most contentious issue in US too) #FDADTC
• SH: main reason HGC went with guiding principles as opposed to (binding) code of practice? Nobody to enforce code of practice #FDADTC
• SH: the revised HGC recommendations were designed with an int’l market in mind, along with participation from DTC industry #FDADTC
• HGC updated its report, recommendations last year w/ “A Common Framework of Principles for DTC genetic testing http://bit.ly/ePPe6j #FDADTC
• SH describing story of Sciona, HGC public consultation on DTC genetic testing (see: http://bit.ly/eOVKf7) #FDADTC HT @eurogene @RDGene
• SH shifting now to soft law approaches: voluntary codes of practices, guidelines, etc. UK has engaged this route frequently #FDADTC
• (Australia’s model is what FDA’s LDT guidance could very well resemble see: http://bit.ly/b8Fr3j #FDADTC)
• SH: TGA participates in standard setting, can intervene if there is a concern. #FDADTC
• SH: AUS classed LDTs as med devices; high-risk reviewed by TGA (FDA equiv); med- & low-risk registered w/ TGA, eval by industry. #FDADTC
• SH now looking at Australia’s new IVD regulatory framework; restricts certain types of IVD self-testing (incl. genetic traits) #FDADTC
• SH: European Commission has suggested there might need to be special measures for DTC genetic testing #FDADTC
• SH’s overview of EU device regulations – the current ones aren’t very good; but European Commission attempting to strengthen #FDADTC
• SH: if we want to stop “bad tests getting on the market” we need to look to IVD regulations. Comparing EU, AUS, US #FDADTC
• SH: does not know of any enforcement activity of genetic testing regs in any of these countries, apart from South Korea #FDADTC
• SH: common themes: restrictions on who can test, standards on genetic testing, some tests more imp than others (e.g., screening) #FDADTC
• SH: South Korea apparently has a blanket ban on DTC genetic testing #FDALDT
• (Incidentally, I agree with SH: sometimes surprisingly difficult to get info on int’l regulatory developments, esp outside of EU #FDADTC)
• SH now flitting out of Europe & over to South Korea (although caveats that he has not confirmed the data); SK banning some tests #FDADTC
• SH: most recent piece of legislation is Germany’s genetic diagnosis act. (For detailed GLR coverage, see here: http://bit.ly/gXMgkg) #FDADTC
• (Most of the legislation/regulation SH is discussing also share common themes of informed consent, clinician involvement, bioethics #FDADTC)
• (Note that most of the legislation SH is discussing is quite old, esp by DTC timelines – e.g., Belgium’s dates from ’87 #FDADTC)
• SH now shifting to nat’l legislation efforts on genetic testing (mostly in Europe) – whirlwind tour #FDADTC
• SH: Current status of CoE protocol? So far only 5 member states have signed protocol, & only 1 has ratified. So not yet implemented #FDADTC
• SH: CoE generally permits genetic testing only w/ direct clinical supervision; some exceptions, but not if clear clinical importance #FDADTC
• SH’s next stop: Council of Europe Additional Protocol on Genetic Testing (2008, see http://bit.ly/i8ReIE) #FDADTC
• SH: OECD now discussing how to revise guidelines. One q: is WGS opening up new issues that require revision? (My answer: absolutely) #FDADTC
• SH: int’l treaties standards developed. Starting w/ proposal from OECD (see: http://bit.ly/fS7I27) & supplement implementation #FDADTC
• SH tackling recent developments from all over the world – Germany, UK, Japan, Aus. (Ambitious proj, given diversity of approaches) #FDADTC
• SH: what are our options? Do nothing; ban it; or set some rules (feat. a slide with 10 commandments. FDA guidance from on high?) #FDADTC
• SH: outlining gaps in regulations, including devices, labs. Many countries don’t have anything as comprehensive as CLIA. #FDADTC
• SH: where does DTC fit in existing regulatory landscape: med devices (FDA), lab devices (CLIA), codes of practice (soft law) #FDADTC
• SH: DTC has become focal point for regulation of genetic testing – a debate that dates to at least the 90s (IOM report) #FDADTC
• Now up at #FDADTC, Dr. Stuart Hogarth, Kings College on “Regulating consumer genetics – an overview of global trends”
• DTC company @23andMe has posted its presentation materials in advance of #FDADTC meeting: http://bit.ly/dLnFzJ
• TM: “I’m not that familiar with the type of claims these [DTC] companies are making” #FDADTC
• Thankfully, #FDADTC panel now pressing TM for how DTC is using this GWAS data, whether DTC cos’ claims match the data
• (TM finishes w/, by my count, a single tangential ref to DTC. Think a missed opportunity to tie NHGRI’s scientific expertise to #FDADTC)
• TM: several limitations of GWAS-identified markers for risk assessment – non-determinitive, don’t explain full variability, etc. #FDADTC
• TM now moving on to “the case of the missing heritability” at #FDADTC, with nice HT to @bmahersciwriter
• (TM’s comments on GWAS/SNP discovery also yet to address relationship to DTC – what is being tested, quality of testing, etc. #FDADTC)
• (TM’s talk on history/state of GWAS quite comprehensive. Let’s hope she turns forward to WGS tech, implications before time is up #FDADTC)
• “Cue Music: stuck in a (regulatory) moment. The FDA & oversight of DTC genetic tests” http://bit.ly/eCKjvv @DNAlawyer’s thoughts on #FDADTC
• TM now discussing HapMap. Diving deep into underlying science (although slides on HapMap, seq cost, GWAS associations 4 years old) #FDADTC
• TM: providing the panel with a high-level overview of GWAS methodology, progress over past 5-10 years. (Reflects diversity of #FDADTC panel)
• Now up at #FDADTC, Teri Manolio from NHGRI. Starts w/ scientific basis – relationship between GWAS and DTC
• Panel q: what is a “medical claim”? LM: any claim that arises from a device deemed to be a medical device under FDA regs #FDADTC
• (So does that mean LM/FDA have determined that anything DTC is inherently a medical device & subject to related regulations? #FDADTC)
• LM: we have “already determined” that “enforcement discretion” is not an appropriate model for DTC testing #FDADTC
• LM: very difficult for FDA to track the DTC market; continually having to scan the web & other sources to determine who is out there #FDADTC
• Panel q for LM: how “massive” is this DTC problem, really? LM: were far more companies; believe a number have left DTC model behind #FDADTC
• (Overall, LM’s talk comprehensive background, well-balanced. FDA hitting right notes at opening of #FDADTC)
• Panel q to LM: is the consumer the person ordering the test, or the person whose DNA is tested? LM: expects them to be the same… #FDADTC
• (You can find full text of 3 questions to #FDADTC panel on pg 4/6 here: http://1.usa.gov/h6WYm3)
• LM: 3 primary qs to panel: risks/benefits of (1) clinical DTC w/out MD, (2) possible misunderstanding, (3) scientific standards #FDADTC
• LM: so why is FDA here? To here discussion/perspectives from panel, public. Wants discussion of “difficult issues” in #FDADTC
• LM: FDA must do this while keeping up with technology, promoting innovation #FDADTC
• LM: regardless of who orders a test, it is essential that FDA determine medical claims are correct & valid #FDADTC
• LM: WGS now “widely available” – WGS platforms’ performance not well understood; none are cleared by FDA #FDADTC [though cos working on it]
• LM providing overview of tests avail DTC, incl. clinical/non-clinical distinction. FDA focused on tests meeting def of med device #FDADTC
• (Good to see Mansfield acknowledge inevitability of WGS, changes in DTC models/marketplace. #FDADTC)
• LM: number of DTC companies has “likely narrowed” due to FDA’s oversight; but technologies (inc. WGS) are changing the field #FDADTC
• LM: working w/ DTC companies to comply with medical device regulations; has been a challenge for both FDA & companies #FDADTC
• LM: “There is a place for DTC genetic testing, but appropriate oversight should apply to [protect individuals]” #FDADTC
• LM: today, DTC remains as business model. Aware of various public positions pro/con on DTC. #FDADTC
• LM: on 2010 GAO report – “FDA briefed generally, not aware of specific findings in advance of House hearing” #FDADTC http://bit.ly/bfF7we
• LM: 2010, FDA sends numerous more “letters to industry” – many companies exit DTC market, others develop compliance plans w/ FDA #FDADTC
• LM: 2010, FDA learns of Pathway/Walgreens (http://bit.ly/uZQa9), sends “letter to industry” & meets w/ Pathway. Concl: DTC = risks #FDADTC
• LM: in 2009, FDA began sending “it has come to our attention letters” and meeting with DTC companies – cos claimed LDT status #FDADTC
• (For a fuller overview of the background Mansfield is providing, see this post http://bit.ly/hfZquo #FDADTC)
• LM: 2007, we moved beyond nutrigenetic; CLIA issues; state (NY/CA) enforcement #FDADTC
• LM: starting off the history of DTC, all the way back to…2006. (We haven’t been at this all that long) #FDADTC
• Mansfield: def of DTC: tests ordered directly by individual, w/out prescription; results received by individual without help of MD #FDADTC
• Now up, Dr. Liz Mansfield: “Why are we here? History and current landscape of DTC genetic tests” #FDADTC
• (Unfortunately, there is no live webcast at #FDADTC)
• Kicking off #FDADTC mtg here in DC: http://bit.ly/iiJIC0 Right now, reviewing exec summary: http://1.usa.gov/h6WYm3
• Also, for those who are interested, I’ve posted my #FDADTC slides in advance of tomorrow’s talk: http://bit.ly/fcPUyI
• GLR Post: Charting a Path for DTC Oversight: http://bit.ly/iiJIC0 My thoughts in advance of the #FDADTC meeting
• RT @dgmacarthur: I adopt a tone of cautious optimism in advance of tomorrow’s FDA meeting on DTC genetics: http://bit.ly/fSkRYl
• Meeting materials for tomorrow’s #FDADTC mtg here: http://1.usa.gov/i24b7F If anybody knows of a webcast link, please lmk.

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

• Interesting. Dx version would be welcome: MT @BiotechPatent: Bipartisan Congressional #MedTech Caucus launches website: http://bit.ly/fbUeil
• RT @matthewherper: A Cancer Patient’s Quest Hits DNA Pay Dirt — or why Kathy Giusty and 38 genomes are so important. http://ow.ly/4lEuE
• RT @LifeSciVC: Not all about Tech; >200 new healthcare, wellness & life sci startups on AngelList. Pretty cool. @naval http://ow.ly/4l3wW
• RT @pgx_reporter: Celera Will Add to Quest’s MDx Capabilities; But Reimbursement Questions Cloud Revenue Contribution: http://bit.ly/gxJOOZ
• Part 2 of @Xconomy guest post on who will pay for drug development: http://bit.ly/gpvD3j
• RT @genomesunzipped: How does adding extra genetic information change our disease risk? @anderson_carl finds out: http://bit.ly/g6X4C3
• RT @ldtimmerman: SV Life Sciences, flush w/new $500m fund, on the hazard of having lots of dough when VC is struggling. http://bit.ly/ekMwbu
• Venture capitalists (via NVCA) concerned about impact of patent reform on inventors, start-ups: http://bit.ly/ed4cqA Cont. to wait on House.
• GLR Post: Considering the Impact of Yet Another Proposal for Genetic Legislation http://bit.ly/egqzi8
• RT @InSequence: BGI’s Sequencing Projects Tackle Genetic Roots of Cancer and Disease, Reference Organism Assembly: http://bit.ly/fatypL
• What’s next for CardioDx? CAD test adoption (here & in BRIC countries) + more/predictive tests. But no IPO: http://bit.ly/hoXNCs
• AMA lashes out against DTC genetic testing: a “weapon” & the “unauthorized practice of medicine”: http://bit.ly/dGeMJk HT @5amsolutions
• RT @GenomeInstitute: @GenomeInstitute’s Dr. Elaine Mardis interviewed about latest breast cancer sequencing work http://bit.ly/hwK5Rr
• Sequence Analysis 101: A newbie’s guide to crunching next-gen seq data: http://bit.ly/gVX6CL feat @dgmacarthur HT @gw_dailyscan
• Who’s Going to Pay for Future Drug Development (Part 1): http://bit.ly/fGV0Q8 in @Xconomy
• RT @dgmacarthur: Cool – @23andMe has used its participant data to find novel genetic associations with Parkinson’s: http://bit.ly/fvYENB
• Alnylam, UMass, and Others Settle RNAi Patent Litigation: http://bit.ly/dRjafg (from 3/15)
• Missed @Xconomy interview by @BVBigelow w/ social networking researcher James Fowler, who is working w/ @23andMe: http://bit.ly/esnwEV
• Thoughts from CardioDx, Genomic Health & others on challenges of commercializing genomic diagnostics (from 3/16): http://bit.ly/e1r6F6
• A reminder from @DNAlawyer that not all gov’t regulation (incl. #FDADTC) is necessarily authorized or unchallengeable: http://bit.ly/hBPzO9
• RT @GenomeWeb_News: AstraZeneca, @Sagebio Partner on Cancer Therapeutic Development: http://bit.ly/dIrFdK
• Last wk’s House jobs forum reminder some in DC see #FDADTC regulation as inhibiting job creation: http://bit.ly/fjLXwJ cc @PathwayGenomics
• Report from @PHGFoundation: Fair access to genetics needed in mainstream medical services http://bit.ly/dSSD7k
• RT @drjonboyg: get this job & be my boss. MT @girlscientist: Job open: NHGRI, Chief Policy & Program Analysis Branch http://is.gd/FBHOED
• Guest Post by @Navigenics GC: “Breast Cancer Counseling: Personalizing Med. Beyond BRCA Testing” http://tinyurl.com/65tct3o cc @alliejanson
• A new DTC entrant: RT @Lumigenix: Until 3/31 our Introductory kit is only $99 USD (normally $279). http://bit.ly/fVU7UK
• RT @genomesunzipped: Analysing your own genome, bloggers respond to the FDA and more reporting on bogus GWAS results http://bit.ly/fP4FtK
• RT @InSequence: BioNanomatrix Pockets $23.3M in Series B Funding http://bit.ly/fO9jHb
• BTW, that may be 1st attempt I’ve seen at valuing a personal genome. $20/day + 10% of earnings for an @kennethreitz clone
• Another github genome, this time with an extremely forward-thinking (& ambitious) license provision: http://bit.ly/i5h6Ev
• Looking forward to the first Science Online NYC event next month: http://bit.ly/eAr3tX cc @S_O_NYC #sonyc
• More $ for OCR necessary? 250 breaches affecting >500 ppl (http://1.usa.gov/bxVDO3) & >10K total breaches say yes.
• OCR requests an additional $5.6M for HIPAA/HITECH enforcement: http://bit.ly/eMBBFp
• RT @PersonalizedMed: Take home msg from HUGO 2011 Dubai: global community in #genomicmedicine engaged , growing, active, entrepreneurial
• An admittedly cynical take on angel investing RT @JCainHart: The Top 12 Lies Angels Tell | http://read.bi/fTzZHM
• A first look at HBM’s survey of ’10 Biotech M&A trends by @LifeSciVC: http://bit.ly/eEw5ie More deals, smaller buyers, worrying multiples
• A look at Europe’s complicated regulatory environment for genetic testing in EJHG: http://bit.ly/gT8AEI congrats to lead author @eurogene
• Good to see BGI (@BGI_Events) taking on ethical challenges of WGS & personal genomics: http://bit.ly/erSNKs cc @PGorg
• RT @GenomeWeb_News: JGI Taking Proposals for Sequencing Projects: http://bit.ly/hU2zfv
• RT @GenomeWeb_News: Ambry Genetics, LABS Partner on Genetic Testing: http://bit.ly/hniLM5
• “The Structure of the MedTech Innovation Ecosystem” http://bit.ly/eqogIh Interesting slidedeck by Josh Makower HT @dgmacarthur
• Obama to push for privacy bill of rights (http://on.wsj.com/fG3THT). Will it encompass genetic privacy rights (http://bit.ly/i9fIT5)?
• Uninformed Consent: Tech Solutions for Faulty Permissions in Health Care http://bit.ly/gloWak in @sciam HT @jasonbobe
• GLR Post: Is the Genetics Rights Movement Picking Up Steam? http://bit.ly/i9fIT5 (review of VT legislative proposal)
• RT @CAPDCAdvocacy: AMA releases proposed molecular pathology codes for stakeholder review: http://tinyurl.com/45uw32w
• Including a “buy” for $MYGN: RT @GenomeWeb_News: Investment Firm Jefferies resumes coverage on 8 MDx & other firms: http://bit.ly/gzi0JD
• Having struck out w/ Bayh-Dole (http://bit.ly/ge6VUZ), Fabry patients file class action suit against $GENZ, Mt. Sinai: http://bit.ly/ghc6bE
• Agreed! A great day & very timely discussion. RT @PersonalizedMed: @genomicslawyer thanks for a great day today @DukeIGSP
• RT @girlscientist: Genetics Society of America launches “fully open access journal, with data availability” http://www.g3journal.org
• Wonder who’s buying at $9,500. RT @shwu: “Consumers can’t decode genomics-based tests on their own” says survey: http://bit.ly/fm9LNO
• RT @GENbio: North Carolina & MD trying to create new funds designed to assist life science start-ups. http://bit.ly/fcnXrV cc @JCainHart
• RT @LifeSciVC: More on $50M Slate drug cost to NDA “Choose your Own Numbers: Crowdsourcing Cost-to-Produce a new Drug?” http://bit.ly/hMya4G
• $GNOM Expects to Ship >500 Genomes in Q1, Plans to Break $5K Genome Price by Year-End: http://bit.ly/fsTnFc via @InSequence
• RT @EdwardWinstead: Making Genome Sequencing Part of Clinical Care http://bit.ly/eBFFtL by @emilysinger via @EricTopol
• RT @ldtimmerman: Gates Foundation makes 1st direct equity investment in a biotech co, Liquidia Technologies. http://bit.ly/fwyfIq
• RT @David_Dobbs: Buckle up. RT @dgmacarthur: Watching James Watson present to packed house … in Francis Crick auditorium @sangerinstitute.
• RT @pgx_reporter: Goldman Analyst: $MYGN’s Stock Buyback Suggests Slowing Organic Growth: http://bit.ly/fqXDnR
• RT @dgmacarthur: Five more @23andMe data-sets in the public domain: @manuelcorpas and family follow @genomesunzipped: http://nblo.gs/f6YjM
• RT @genomesunzipped: Our raw genetic data are now officially in the public domain, under Creative Commons CC0: http://bit.ly/gWDiUR
• RT @jasonbobe: GET 2011 @ UPenn, speakers incl Goldstein (Duke), Pe’er (Columbia), Drmanac (CGI) & Church (Harvard): www.getconference.org
• Dell survey: Patients like idea of health IT & digital data (81%), even as concerned about privacy (69%) http://bit.ly/fNjoI2 HT @cwhogg
• Sad but true: “best-case scenario” RT @NatureNews Modest cuts for science in Senate compromise bill http://goo.gl/fb/BXkxN
• TED not on today’s agenda? Go see @MishaAngrist at BIL instead: http://on.wsj.com/gQFI0y
• RT @genomesunzipped: Inbreeding around the world, gene-environment interactions and sales of genetic tests: http://bit.ly/dYp6y6
• RT @FierceBiotech: Careers in biotech ranked as the No. 1 happiest job in America. http://on.msnbc.com/hJpa98
• RT @GenomeWeb_News: Europe, EMBL Pledge Continued Partnership: http://bit.ly/g8csIF
• RT @MattMealiffeMD: #FoGMIV: increasing # of studies show N=1 seq of individual pt’s tumors yield info w/ at least quasi-clinical importance
• Fighting Gravity in Venture-Backed Biotech Returns: http://bit.ly/g8G7Ds by @LifeSciVC
• RT @bigs: RT @raymondmccauley: Audience doc: Why “patients”, “consumers”, “organizers”? We’re all just people, looking at ourselves. #FoGM11
• RT @GenomeWeb_News: Patent Reform on Cusp of Senate Passage: http://bit.ly/hgLX5I
• RT @InSequence: Affymetrix Dismisses Lawsuit against PacBio, Former Employees: http://bit.ly/g6r78H

What should we make of this three state “groundswell?” Although not identical in scope or substance to the Massachusetts Genetic Bill of Rights (“MA GBR”), both the Vermont and California proposals appear to reflect a concern (shared by the MA GBR) that, at least when it comes to the use and misuse of genetic information, the current system of federal oversight is inadequate. Then again, as the legislative findings section of the California proposal (pdf) puts it, perhaps “the current explosion in the science of genetics” simply “compels legislative action in this area.”

Today we’ll dig into Vermont’s proposed H.368: “An act relating to privacy of genetic information” (pdf) (the “Vermont Act”). Next week, we’ll tackle California.

The Value of a Genome. In many respects the Vermont Act closely resembles the MA GBR we covered in detail last month and shares its emphasis on genetic information as a personal property right.

Nowhere is this clearer than where, matching the MA GBR word-for-word, the Vermont Act proposes the insertion of a new provision into Vermont’s existing genetic testing statute, declaring “genetic information the exclusive property of the individual from whom the information is obtained.” 18 V.S.A §9330 The Vermont Act goes on to confer upon genetic material the status of “ real¹ property subject to one’s individual control and dominion in accordance with generally held precepts of property law in Vermont.” 18 V.S.A. §9336(a)

After codifying property rights in genetic information, the Vermont Act, just like the MA GBR, goes on to require that any individual engaged in genetic research or commerce be “made aware both orally and in writing that his or her donation is a commodity and is of some material value.” And if the transaction of genetic information occurs in a for-profit context, the individual would be entitled to “compensation at fair market value.” 18 V.S.A. §9336(c) To be sure, we’re still no closer to articulating a valuation method for genetic information than when the idea was first proposed in Massachusetts earlier this year.

Ambition vs. Reality. There are also a few areas where, in its zeal to protect individual genetic rights, the Vermont Act goes a step too far and appears to conflict with federal law, with potentially problematic (or at least confusing) results.

For example, the addition of 18 V.S.A. §9336(d) would provide that:

Any report or record produced by or stored at a hospital; dispensary; laboratory; hospital-affiliated registry; physician; commercial genetic testing company, agency, or association; or insurance institution or its representative pertaining to any genetic information is the exclusive property of the individual sampled or analyzed. Such report or record shall not be considered to be a public record, and the contents thereof shall not be divulged by any person having charge of or access to the report or record without informed written consent… (emphasis added)

While there are three minor exceptions to §9336(d), none would save the provision from a nasty conflict, at least on its face, with other federal laws, including the Health Insurance Portability and Accountability Act (HIPAA).

Under HIPAA, covered entities (including healthcare providers, such as hospitals and physicians) and their business associates are not required to obtain prior consent for certain uses and disclosures (e.g., for treatment, payment and health care operations) of protected health information, including genetic information. The prior consent requirement was removed under HIPAA in certain instances due to its unintended effect of preventing “timely, quality health care to individuals in a variety of circumstances.” The Vermont Act’s supporters should take another look to ensure that §9336(d) would not produce the same unintended effect under Vermont law.

Next is §9336(e), an even broader and more confusing provision:

Information derived from the sequence of the human genome shall be part of the public domain and shall not be considered the property of any individual. Nothing in this chapter shall be construed to grant an ownership right to any individual or entity utilizing the publicly held information from the sequence of the human genome in the furtherance of the creation of a venture or enterprise, including any genetic goods, products, or services.

At first blush, this appears to be more of a statement of policy by the Vermont Act’s sponsors than a statement of law. §9336(e) refers to “the sequence of the human genome,” not a sequence of a human’s genome, and the term “genome” does not appear in the Vermont Act (or in Chapter 217 of the V.S.A.) outside of this single proposed provision.

While efforts to place genomic information in the public domain – including the work of Genomes Unzipped, the Personal Genome Project, SNPedia and The Sage Commons, to cite several such public genomics projects in which we are actively involved – are laudable, mandatory public genomics is not exactly the provenance of the Vermont state legislature.

Or perhaps this is just Representatives Pearson and Wizowaty’s way of asserting their support for the plaintiffs in the ongoing Myriad gene patent litigation by asserting, more than a decade after the fact, that none of the Human Genome Project’s fruits shall be patentable. (Although here, too, Vermont would be treading far outside the scope of its legislative authority.) Either way, this is one provision of the Vermont Act that will need to be either clarified or axed before passage.

Consumer Protection. The Vermont Act comes back to earth, and in line with the MA GBR, in proposing the addition of 18 V.S.A. §9339 and §9340, which together restrict the use of genetic information in marketing and instruct the “consumer protection unit in the office of the attorney” to “investigate and prosecute complaints relating to genetic goods, products, and services.”

As we have argued in the past, when it comes to the burgeoning field of genetic and genomic commerce, one logical and welcome form of regulation would be increased oversight from consumer protection agencies, including both state-level enforcement, as proposed by the Vermont Act, and increased national-level oversight from agencies like the Federal Trade Commission (FTC). (While the possibility of FTC oversight for genomic commerce was back in the news last week, specifically in conjunction with the FDA’s public meeting to discuss direct-to-consumer genetic testing, there are also numerous other areas of genomic commerce that might benefit from increased oversight from consumer protection agencies.)

§9339 also explicitly prohibits “genetic profiling,” which includes any effort to link an individual’s “demographic information” to her “genetic information or genetic material for marketing purposes.” However, the provision would not prohibit marketing on the basis of genetic data if those data were aggregated, did not contain identifying information and could not be used, “directly or indirectly, to obtain identifying information.” That would seem to be a fairly broad safer harbor for would-be “genetic profilers,” but given the inherent difficulty in ensuring that seemingly de-identified genetic information, even when aggregated, won’t be re-identified, this marketing safe harbor might prove to be rather limited in practice.

GINA’s Gaps, Again. As we noted in examining the MA GBR, the Genetic Information Nondiscrimination Act of 2008 (GINA) contains several gaps in its prohibition of insurance discrimination. Notably, while prohibiting healthcare insurers and employers from discriminating on the basis of genetic information, GINA does not address the use of genetic information in long-term care, life or disability insurance.

Even prior to GINA’s passage, Vermont was one of a handful of states with relatively robust statutory protections against genetic discrimination in insurance. Under current Vermont law (18 V.S.A. §9334), no insurance policy—including long-term care, life and disability insurance policies—may be “underwritten or conditioned on the basis of” a required genetic test of an individual insured or the results of a genetic test of any member of the individual’s family. §9332, however, currently permits insurers to require genetic testing in situations where doing so would not violate §9334.

The Vermont Act would revise §9332 to prevent insurers from requiring genetic testing in any setting, regardless of whether it would violate §9334. In combination with §9332(d), the Vermont Act would prevent any insurer from soliciting genetic testing without first obtaining “prior written authorization and informed consent,” including providing a warning that the results of such test might become part of the individual’s permanent medical record or materially impair the availability of insurance benefits. The Vermont Act would not, however, deny such solicitations by insurers outright.

The Vermont Act would also prohibit places of public accommodation (9 V.S.A. §4502) and financial institutions supplying credit (8 V.S.A. §10403) from discriminating on the basis of genetic information.

What does it mean? As with the MA GBR, it is crucial to emphasize that the Vermont Act is a legislative proposal and not current state law. We do not know what level of support the Vermont Act enjoys within the state legislature but, should it pass, the implications—both good and bad—would be substantially similar to those we discussed in our review of the MA GBR.

Next week we’ll examine another legislative proposal, from California, and ask whether these recent developments represent a groundswell of support for more robust genetic privacy legislation.

—————————————————————

¹ The text of the Vermont Act says “real property,” although this would seem to be a clear mistake as real property or real estate refers to land and not to personal or intangible property.

On Monday, the twelve founders and co-collaborators at Genomes Unzipped (including me) published our genetic data for the world to see. We released both raw data and a custom genome browser. This morning we began the process of talking about the experience of joining the public genomics movement, something that has already affected each of us in different ways. My first post discusses why my decision to join Genomes Unzipped was not a purely personal decision.

On Tuesday, the Personal Genome Project unveiled its latest phase, announcing the enrollment of its next 1,000 participants (the “PGP-1K”), integration with Google Health for phenotype collection and sharing, the upcoming release of a number of new, public whole-genome sequences and several other exciting developments.

It has been a big week for personal genomics, and I am gratified to be involved in both of these projects. Onward and upward or, as Jason Bobe might say, “to the moon!”

The software-based test can be downloaded from the website of the University of Maryland’s Center for Bioinformatics & Computational Biology, where Salzberg is the director and Pertea is on the faculty. The test purports to test genomic sequence data against a set of known mutations in the BRCA genes. In addition to representing a conceptual alternative for those seeking to evaluate their risk of hereditary breast cancer, the so-called “Salzberg Screen” is also a direct challenge to Myriad Genetics, the FDA and the existing legal, regulatory and policy regimes that continue to struggle to keep pace with the science and technology of genomics and personalized medicine.

Below, we examine how the Salzberg Screen fits—or does not—within the current legal and regulatory landscape, as well as what it signals for the future of do-it-yourself genomics, whole-genome sequencing and the law.

BRCA Background. First, a quick primer on the clinical and legal significance of the Salzberg Screen’s target: the BRCA genes. BRCA-1 and BRCA-2 are perhaps the two most well-known human genes. This stems in part from the role which mutations in those genes play in dramatically increasing the risk of breast and/or ovarian cancer for certain individuals.

The notoriety of the BRCA genes has also been significantly enhanced in the past year thanks to high-profile litigation in both the United States and Australia challenging the validity of the BRCA gene patents held by Myriad Genetics. Myriad’s patents covering the isolated BRCA-1 and BRCA-2 genes, as well as certain methods of diagnosing breast cancer susceptibility, were ruled invalid by Judge Robert Sweet of the Southern District of New York earlier this year. Judge Sweet’s opinion is currently being appealed to the Court of Appeals for the Federal Circuit, where hearings are expected to get underway later this fall. Despite the litigation, Myriad’s BRCA patent portfolio has enabled it to serve as the sole (lawful) provider of BRCA screening in the United States and numerous other countries worldwide.

The Salzberg Screen. Myriad’s role as exclusive provider of BRCA screening is a fact that has clearly irked both Salzberg and Pertea:

We believe that any individual should be allowed to interrogate his or her genome for all mutations of interest, regardless of whether a private company claims to ‘own’ the rights to particular gene mutations. To challenge the restrictive gene patenting system, we have developed a computational assay that, as a proof-of-concept, tests for 68 known variants of the BRCA1 and BRCA2 genes. In other words, we empower any individual using our software (whether this is a private individual, a clinician or a clinical or basic researcher) to test for these mutations and circumvent the gene patents.

The Salzberg Screen compares whole-genome sequence data (or, presumably, data from targeted sequencing of the BRCA genes) against a list of “68 known mutations in the [BRCA] genes” drawn from the Online Mendelian Inheritance in Man (OMIM) database. Salzberg and Pertea readily admit that their DIY screening tool is far from perfect, noting that “…the 68 mutations used in this proof-of-concept assay do not represent a comprehensive list of BRCA mutations,” but pointing out that “additional mutations could easily be added to our test…”

In addition to only testing for a fraction of the publicly identified BRCA mutations, a number that does not include additional proprietary information about BRCA mutations possessed by Myriad Genetics, the Salzberg Screen also possesses another significant current limitation: cost. Myriad’s BRACAnalysis test costs several thousand dollars, but it includes targeted sequencing of the individual’s BRCA genes. While the Salzberg Screen is free to use, it requires the user to come up with her own whole-genome sequence data.

At the moment, whole-genome sequencing is still more expensive than Myriad’s BRACAnalysis, a test which is covered by many insurers where clinically indicated. The price of a whole-genome sequence is a moving target and depends upon the quality of the sequence (including accuracy and depth of coverage), whether it is generated in a clinical (i.e., CLIA-certified) or research facility, the level of associate interpretation or analysis that is provided and a host of other factors. Current best estimates put the cost at anywhere from $1,000 to $10,000 per genome, although Salzberg and Pertea, like so many others, note that we are “rapidly approaching the day when it will be cheaper to fully sequence a genome before testing the sequence for all known genetic mutations associated with a given disease than to conduct multiple separate tests for each disease.”

While that day is not quite at hand, Salzberg and Pertea’s goal is not to create a computational screen that is a replacement, right now, for Myriad’s test. Instead, they have developed a “…template that can easily be modified to test for almost any known genetic mutation,” and thereby one day circumvent not only Myriad’s testing monopoly, but also all human gene patents.

What This Means, Part I: Myriad and its Patents. More than a year ago we wrote about the impending collision between single gene sequencing, such as that provided by Myriad, and inexpensive whole-genome sequencing (see: Whole-Genome Sequencing and Gene Patents Coexist (For Now)). As the cost of gene sequencing continues to fall, we expect that more and more software-only tools like the Salzberg Screen will spring up. But can such tools be used, as Salzberg and Pertea hope, to “empower any individual…to test for [BRCA] mutations and circumvent the gene patents”? More pointedly, can such tools circumvent gene patents legally?

Infringement, Direct and Indirect. A patent can be infringed in two ways: directly or indirectly (see Section 271 of the Patent Act). Direct infringement consists of someone making, using, offering to sell, or selling the patented product or process. Usually, the infringer must be duplicating the patented invention exactly as described in one of the patent claims; in patent jargon, the infringed patent claim must “read on” the infringer’s activity, element-by-element. Indirect infringement comes in two forms: inducement and contributory infringement. Inducement, sketchily codified in Section 271(b), requires knowledge of the patent and an affirmative act to cause or direct a third party to carry out an act of infringement. In other words, you can’t escape liability by contracting with someone else to make a patented product or carry out a patented process. Contributory infringement, codified in considerable detail in Section 271(c), usually consists of selling a component of a patented invention, knowing that the component has no use except in that invention. The theory here is to prevent a conspiracy of infringers from escaping liability by individually selling pieces of the protected invention. Significantly, you can’t be guilty of indirect infringement unless someone is engaging in direct infringement.

So the first and most important question here is whether use of the Salzberg Screen would result in someone infringing one or more of Myriad’s patents. That is, would either the individual or someone else (for example, a clinician or genetic counselor helping the individual use or understand the Salzberg Screen or a similar service) be making, using, or selling a product or process covered by a Myriad patent? (This whole analysis assumes, of course, that the relevant Myriad patents are not ultimately found invalid at the conclusion of the ongoing Myriad litigation.)

It’s worth remembering that Myriad’s patents include both product and process claims. On the product side are claims like Claim 1 of U.S. Patent 5,747,282 (pdf):

An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having [a listed] amino acid sequence.

Would anyone in the chain of use of the Salzberg Screen be making or using this gene in isolation? That is a factual, scientific question that turns on whether the particular sequencing technique involves using “the gene.” Our science sources tell us that the answer depends on the sequencing method, but, at least for whole-genome sequencing, it is probably “no.” (Sequencing just the BRCA genes, as opposed to whole-genome sequencing, would likely be a different story.)

There are also claims like Claim 5 of the same patent: “An isolated DNA having at least 15 nucleotides of the DNA of claim 1”—i.e., any 15-mer oligonucleotide that can be found in the patented gene. While almost no one expects a claim like this to survive in the Federal Circuit, if it did, then almost any sequencing process might infringe solely as a matter of statistical probability (pdf).

A Method of Inducement? On the process side, Claim 1 of U.S. Patent 5,709,999 (pdf) is one of the broadest. Here is how the claim reads:

A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Tables 12A, 14, 18 or 19 in a human which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 cDNA made from mRNA from said human sample with the proviso that said germline alteration is not a deletion of 4 nucleotides corresponding to base numbers 4184-4187 of SEQ ID NO:1

And here is how Judge Sweet, in his Myriad opinion (pdf), translated that claim, shortly before finding it to be invalid:

Claim 1 of the ‘999 patent is directed to the process of ‘analyzing’ a BRCA1 sequence and noting whether or not the specified naturally-occurring mutations exist. The claimed process is not limited to any particular method of analysis and does not specify any further action beyond the act of ‘analyzing.’”

Under that reading, would Claim 1 of the ‘999 patent cover the activities of an individual who downloaded and ran the Salzberg Screen in order to “analyze” their BRCA-1 sequence? Would it cover the activities of a clinician or genetic counselor assisting a user in interpreting the Salzberg Screen’s results? That would be a matter for a court to decide, although it is certainly possible that, depending on the specific court and specific set of facts, the answer could be “yes.” If so, there would be an act of direct infringement.

If a court were to find an act of direct infringement, then Salzberg and Pertea could well be liable for indirect infringement, most likely in the form of inducement of infringement.

A Calculated Gamble? Salzberg and Pertea are clearly aware of the Myriad patents (a requirement of inducement) and explicitly invite individuals to “test for [BRCA] mutations and circumvent the gene patents.” They also readily acknowledge that they are asking Salzberg Screen users to commit patent infringement.

In creating this software, we are not violating the BRCA patents directly but any user would be, because even a noncommercial use (such as examining one’s own genome) is considered to be patent infringement.

The fact that Salzberg and Pertea claim not to be violating the BRCA patents “directly” suggests that they are aware of the risk of indirect infringement. They do not, however, appear to be overly concerned that Myriad will pursue such a claim.

For Myriad to make out a claim of indirect infringement against Salzberg and Pertea, it would likely first have to show that individual users are directly infringing Myriad’s patents. Suing a direct infringer could involve challenging in court the activities of an individual using a freely available software program to examine her own genes from the privacy of her own home.

But Myriad wouldn’t have to actually sue the direct infringer—it could decide to sue only Salzberg and Pertea for indirect infringement. In fact, the whole premise of indirect infringement is that it provides a patent holder an avenue of redress when it isn’t feasible to pursue the direct infringer. Still, given the substantial negative publicity that continues to swirl around Myriad’s BRCA patents, and the fact that suing for infringement would also mean subjecting its patents to a new set of invalidity challenges (a near-certain argument in defense from any alleged infringer), Salzberg and Pertea may be taking a calculated gamble that Myriad simply does not have the stomach to initiate any BRCA patent infringement litigation, whether direct or indirect.

Myriad’s Next Move. Myriad derives 90% of its revenues from its BRACAnalysis product, so neither the company nor its investors are likely to take any challenge to its BRCA business lightly. At present, however, the Salzberg Screen does not pose a credible commercial threat to Myriad. It does not test for the full range of deleterious mutations covered by Myriad’s BRACAnalysis, and it also requires something few people have: access to a high-quality copy of their genome. For those reasons, and in light of the negative publicity that would flock to any attempt Myriad might make to quash the Salzberg Screen, the strong likelihood is that Myriad will simply ignore this development, at least for the moment. What’s more, as Myriad is no doubt aware, pending the appeal of Judge Sweet’s decision invalidating certain of Myriad’s patents, an alleged infringer could use that decision to defend itself under an arcane legal doctrine called “issue preclusion.”

Conceptually, however, whole-genome sequencing has always been a threat for single-gene diagnostic companies such as Myriad. The Salzberg Screen brings that tension into particularly sharp relief. Once individuals routinely have access to high-quality whole-genome sequences, they are likely to ask why they need to pay the Myriads of the world several thousand dollars to analyze a handful of genes when they could pay far less—or perhaps nothing at all—to have the same analysis automatically performed by a software program.

As the technical limitations fade in the face of ubiquitous whole-genome sequencing, the Salzberg Screen, or perhaps one of its descendants (Salzberg and Pertea have created a fully open source piece of software), will come to present a viable alternative to Myriad’s test, at least in certain circumstances (e.g., for second opinion or confirmatory testing). How quickly this will occur remains unknown, but there is a strong likelihood that it will be before 2015, which is when the first group of Myriad’s BRCA patents are set to expire.

In many ways, the Salzberg Screen is every bit the frontal attack on Myriad’s patents that the ACLU-initiated litigation represents.  Like the ACLU litigation, it publicly, deliberately and unapologetically challenges Myriad’s right to control access to BRCA information. Allowed to evolve unchecked, it could one day threaten Myriad’s core business. So even if Myriad takes no action right away, you can safely bet that the company will be watching the development of the Salzberg Screen with considerable interest.

What This Means, Part II: Regulatory Acronym Soup or: WGS means more LDTs go DTC and DIY, creating a problem for FDA. While Salzberg and Pertea focus a majority of their attention on circumventing Myriad’s gene patents, their conclusion recognizes at least one other potential obstacle to widespread adoption of their BRCA screening test:

Finally, we recognize that there may be some controversy about giving ordinary individuals the ability to test their own DNA, without also providing expert genetic counseling.

The “controversy” is a nod to the FDA’s recent and widely discussed proposal to more aggressively regulate not only direct-to-consumer (DTC) and do-it-yourself (DIY) genetic tests, but all laboratory developed tests (LDTs). As we wrote earlier this fall, “recent developments suggest that innovation in personal genomics is an increasingly difficult undertaking.” From Pathway Genomics’ short-lived attempt to offer its product on Walgreens’ shelves, to U.C. Berkeley’s unsuccessful attempt to innovate genomics education by offering non-clinical genetic testing to its incoming freshmen, the recent regulatory climate has been none-too-kind to those intent on thinking outside the box in the personal genomics space.

Salzberg and Pertea are aware, no doubt, of these recent events, but remain resolute in their desire to liberate individuals from the strictures—patent, regulatory or otherwise—that would inhibit personal genomic access:

Nonetheless, the door to this new technology is already open and it cannot be closed. Rather than trying to keep patients in the dark, we need to embrace the technology and work harder to educate both physicians and patients about the power and the limitations of genetic tests.

With the FDA in the middle of developing a formal proposal to regulate all LDTs, including those offered DTC, there’s simply no knowing whether or how the FDA will respond to this development. While we think any immediate and public FDA reaction unlikely, the Salzberg Screen should be setting off alarm bells at the agency.

Regulating Tomorrow’s LDTs Today. At the recent public meeting convened by the FDA to solicit feedback on the agency’s plan to regulate all LDTs, there were two areas of discussion in particular that were defined less by disagreement over how or whether to implement FDA regulatory oversight and more by the creeping suspicion that neither the FDA nor any other regulatory agency is  currently prepared to address the issue: (1) testing based on multiplex or whole-genome sequencing data and (2) software-only bioinformatics or genetic testing services.

After Day 1 of the FDA’s public meeting, we wrote:

What about tomorrow? Another area of considerable confusion, if not necessarily disagreement, was what to do with the coming wave of multiplex diagnostic tests including, ultimately, a proliferation of whole-genome sequence data and corresponding interpretive tools. This was not an issue that the FDA tackled directly, but it was clear in the afternoon question and answer session that many of the panelists, at least, were unsure how the next generation of diagnostic tests would fit into the current (or contemplated) regulatory model. The challenges posed by the next generation of sequencing and bioinformatics tools are hardly new, but designing a regulatory framework equipped to survive the next decade will be one of the FDA’s greatest challenges.

While there is no greater clarity today than there was back in July, the unveiling of the Salzberg Screen crystallizes the importance of addressing these issues today, before the coming proliferation of whole-genome sequence data and associated bioinformatics tools.

The arrival of inexpensive and widespread genomic data will be followed, nearly simultaneously, with an explosion of new genomic-based tools and services prepared to analyze that data. These will not be LDTs in the traditional sense, and many will be unlikely to have any need for a laboratory at any stage. Targeting individuals with data in hand, they may well look like more sophisticated versions of the Salzberg Screen, bringing together data and returning personalized genomic analyses.

The Salzberg Screen is not the first computational test that relies on the individual to supply raw data. A familiar example is the Reynolds Risk Score, which takes as inputs user-supplied risk factors such as blood pressure, cholesterol and family history and then “predict[s] your risk of having a heart attack, stroke, or other major heart disease in the next 10 years.”

The Salzberg Screen adopts a similar DIY model for genomic data. In addition to a number of similar open-source and/or academic tools and projects already in progress (the Personal Genome Project, Genomes Unzipped and DIYgenomics all offer good examples), commercial variants of this model are also in the works. A new California-based start-up, Existence Genetics, recently described its plans to leverage the coming decline in whole-genome sequence data. According to CEO Brandon Colby, although the company today supplies both genetic tests and analysis to patients, “eventually … we see ourselves disengaging from utilizing gene chips completely, disengaging from all lab work, and instead solely being an analysis company.”

Colby, to his credit, recognizes that such a model will undoubtedly attract the attention of the FDA:

Colby said that he expects the agency to provide clear guidelines and regulations for LDTs soon, and when they do, ‘we really do look forward to working with them. The big question is how they’re going to regulate and what the timeline is … but once both of those are worked out by the FDA, we’re going to be front and center and willing to work with them and make sure we comply.’

With the FDA still “trying to decide what [its] options are,” Colby may be more optimistic than most in viewing  “clear guidelines and regulations for LDTs” as likely to arrive “soon.” Regardless of when those LDT guidelines actually do arrive, the more important question remains whether they will provide a meaningful degree of insight into the agency’s plans for reviewing multiplex and whole-genome sequencing products and the software-only bioinformatics services that will be developed to leverage low-cost whole-genome sequencing.

Drawing the Right Lines. The examples presented by the Reynolds Risk Score calculator, Salzberg Screen and Existence Genetics products, among others, challenge us, and particularly the FDA, to carefully establish what constitutes an appropriate regulatory target. As genomic tests and services move out of the laboratory and into the genomics data cloud, where and how will the FDA direct its regulatory energies?

If the FDA focuses on the risk level of the condition analyzed, how will it respond to multiplex or whole-genome interpretations that analyze both high- and low-risk conditions simultaneously? If the FDA seeks to install clinician gatekeepers between data and interpretations, even when those interpretations are not coupled with a laboratory test or other traditional medical device, will the agency also attempt to forbid individuals from accessing or attempting to analyze their medical records or raw genomic data on their own?

Drawing the right lines will be exceptionally difficult, and will require considerable foresight if the regulatory framework now being developed is to be sufficiently flexible to accommodate what are likely to be substantial changes in the way health information is collected, interpreted and delivered. The recently disbanded Secretary’s Advisory Committee on Genetics, Health, & Society (SACGHS), which had been slated to take up the implications of whole-genome sequencing, might well have helped the FDA in this process. Instead, the onus now falls more heavily on the FDA, as well as other public and private regulatory and advisory bodies, to think prospectively and creatively about these issues before the Salzberg Screen and its kin become the norm in personal genomics.

A Final Thought: Keeping Up With the Salzbergs. Even more fundamentally than its challenge to Myriad’s gene patents or to the FDA’s preparedness for a future in which whole-genome sequencing exists alongside do-it-yourself personalized medicine, the Salzberg Screen is a reminder of the Herculean task lawmakers, policymakers and regulators face in attempting to keep up with the pace of scientific and technological innovation in the fields of genomics and personalized medicine.

Whatever we think of Salzberg’s Screen and his aggressive challenge to the status quo of gene patents and federally regulated access to genetic testing, we must applaud the work that Salzberg and others do to continually push forward both the science and the application of genomics and personalized medicine. It’s doubtful that the Salzberg Screen will effectively undermine Myriad’s patents or cause the FDA to wholeheartedly embrace DIY genomics, at least in the short term. But by forcing all of us to think more concretely about such possibilities, Salzberg is spurring valuable discourse and forcing lawmakers, policymakers, regulators and businessmen to respond. We hope that the response, when it comes, will include a recognition that even if we cannot keep up with the Salzbergs—those bent on innovation, no matter how much it strains our current structures—we can do much more, now, to anticipate where they are leading us.

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Note: The image that appears is used and modified with the permission of DIYgenomics.

For those who missed the GET Conference, several high quality recaps are available. The most detailed is A Day Among Genomes, by Carl Zimmer of Discover’s blog The Loom. More targeted reflections on the conference and related events come from Emily Singer of Technology Review summarzing key trends highlighted by the genome pioneers (Singer also has a related piece on the difficulties of understanding human genomes), David Dobbs of Neuron Culture on genomes, cool conferences, and what the hell to tell people about behavioral genes, and Turna Ray of Pharmacogenomics Reporter on the recent Myriad Genetics decision, and its impact on the business of patenting genes. If you’d like even more detail, the Twitter community provided real-time play-by-play.

While there’s no need for a further summary, the GET Conference does provide an occasion to look at the evolving personal genomics landscape in a more holistic fashion.

Genomes GET Personal. Personal genomics refers to the generation and delivery of an individual’s genomic or genetic information. The data itself ranges from testing a single base (referred to as a single nucleotide polymorphism, or SNP) to attempting to sequence each of the approximately six billion bases that make up a human genome. Data generation occurs on a variety of platforms, but it takes more than data to make genomics personal. We must move beyond merely inexpensive genomics to truly personal genomics. That requires analysis of the data, linking it to the life of the individual donor, and, ultimately, using the data in some fashion.

For those of us who frequently read and think about such topics, it’s easy to develop a slightly myopic view of the significance of personal genomics. For example, as Carl Zimmer noted in his review of the GET Conference, it was a challenge to evaluate personal genomics critically “in front of an audience made up of genome scientists, people from the biotech sector, venture capital folks, and other assorted people who are, shall we say, already in the genomic tank.”

The reality is that, to date, personal genomics has been the province of a comparative few. Academic researchers, a fraction of healthcare patients supported by too few providers conversant in clinical genetics, and a handful of companies, entrepreneurs and early adopters striving to deliver genetic information to consumers outside of the clinical setting. But the rest of the world – including a majority of consumers, patients, healthcare providers and payors – is waiting in the wings.

With the cost of generating genomic data dropping, and their possible uses expanding, personal genomics is poised to enter the mainstream. When that happens, certainly by the end of this decade, and possibly far sooner, what will the personal genomics landscape look like? To put it another way, what are the channels or pathways through which ordinary individuals – those of us who are not geneticists or early adopters – will explore their own genomes?

Personal Genomics Pathways. The first step in answering that question is to sketch the personal genomics landscape as it exists today – to understand the pathways through which individuals are currently entering personal genomics.

The following sections outline four different categories of personal genomics: clinical, consumer, research and unintended. Delineating these categoris is not an easy task, and there are frequent examples of companies or technologies that reside in more than one of these four categories. Nevertheless, as the field continues to evolve, mapping the “big picture” can facilitate more precise dialogue, regulatory actions and commercial predictions.

Research. Genomic research is distinguished from the categories described below by its intended use (to improve our understanding of the genetic bases for complex human diseases and traits). But it is important to note that not all genomic research is personal genomic research. This is due to the fact that, in most research settings, genomic information flows in only one direction: from the individual to the researcher. Even aggregate research findings, let alone individualized data, are rarely returned to volunteer participants. Thus, despite the explosion over the past five years of genome-wide association studies (GWAS) and, more recently, the construction of large-scale genomic databases (including the UK Biobank and the Kaiser Permanente Research Program on Genes, Environment, & Health), the vast majority of genomic research does not qualify as personal genomic research.

This is partly due to a timing delay. The proliferation of individual-level genomic research data is a relatively new phenomenon, and research norms have been slow to adapt to a growing body of evidence suggesting that people are interested in learning the results of research carried out using their DNA, and that it is ethical for researchers to return such results. It also reflects some legal uncertainty, specifically whether research conducted (in the United States) in non-CLIA environments can be returned directly to participants without violating federal law. Driven by increasingly vocal calls from both research participants and researchers themselves – including several commentators in the GLR’s What ELSI is New? series – the government agencies that supply the bulk of the funding for genomic research are continuing to examine the issue of genomic data-sharing in the research context.

For the moment, the number of individuals participating in personal genomic research is on the rise. At the GET Conference, George Church provided an update on the Personal Genome Project, which is using unique informed consent protocols to build a research cohort of 100,000 individuals who will have the opportunity to actively participate in personal genomic research, and who will have direct access to their individualized genomic sequence information. The first ten participants (the “PGP-10”) have already made their data available online.

There have also been attempts to develop DTC genomic research initiatives and, while the yields so far have been modest, the model is an intriguing one that promises to involve increasing numbers of individuals in the research aspect of personal genomics.

Clinical. One of the key drivers of the personalized medicine movement is clinical personal genomics. It is defined by its application of genomic data (to clinical care) and its mode of delivering that data to the individual (through a licensed healthcare provider). Extremely wide-ranging, clinical personal genomics has the potential to integrate individualized genetic or genomic information into nearly every aspect of patient care.

Clinical personal genomics includes genetic testing for autosomal dominant genetic traits (e.g., Huntington’s disease), diagnostic testing to predict the likelihood of the development or recurrence of a disease with a known genetic component (e.g., breast cancer) and carrier testing for prospective parents concerned about passing on genetic traits (e.g., cystic fibrosis) to their children. (Arguably, reproductive personal genomics – including carrier testing and other reproductive technologies, such as prenatal testing and pre-implantation genetic diagnosis (PGD) deserve their own category but, since such services are typically offered under the supervision of healthcare providers, they are considered clinical personal genomics in this post.) Clinical personal genomics also involves testing for genetic variants that influence whether and how certain therapeutics will behave in an individual patient, often referred to as pharmacogenetics.

Providers of clinical personal genomics include numerous laboratories offering either FDA-approved genetic testing “kits” or laboratory developed tests (LDTs) (which are not currently regulated by the FDA) targeted at specific genes (as well as at other biomarkers). In addition to the companies that supply the tests or kits, clinical personal genomics also requires genetic counselors, clinical geneticists and other healthcare providers capable of helping patients to understand and act on their genomic data.

A pair of recent announcements by CVS Caremark (acquiring a majority stake in Generation Health) and Medco (acquiring DNA Direct), the country’s two largest pharmacy benefit managers (PBMs), suggest that personal genomics is primed to play an increasingly prominent role in the delivery of medical care. However, there is broad-based concern that there are insufficient numbers of trained healthcare professionals, especially genetic counselors and primary care providers with an adequate understanding of genetics, to handle the expected increase in patients seeking, or needing, clinical personal genomics services.

Consumer. Also referred to as direct-to-consumer (DTC) genomics, the distinguishing features of consumer personal genomics are its intended use (informational, educational or recreational, but not clinical) and its mode of delivery (directly to the consumer, without the requirement of a licensed intermediary).

Consumer genomic services run the gamut from genealogy (Ancestry.com), to paternity (Paternity Experts) to genetic matchmaking (Scientific Match), and everything in between. While some consumer personal genomics services are both popular and uncontroversial (ancestry testing) or are clearly niche products (MyRedHairGene.com), others have straddled the line between consumer and clinical personal genomics, creating confusion for consumers, healthcare professionals and regulators alike.

As an example, 23andMe tests more than half a million SNPs and reports back information relevant to more than 130 traits and conditions, many of which appear unambiguously aimed at influencing their customers’ clinical or medical decision-making. 23andMe also offers a popular genetic genealogy service, and has repeatedly expressed an interest in using its customers as the basis for a personal genomics research platform. What results is a single company with multiple overlapping products that could easily be viewed as a hybrid of the clinical, consumer and research personal genomics types.

What keeps companies like 23andMe in the consumer personal genomics category, at least for the time being, is an insistence on direct-to-consumer access. With a few important exceptions (e.g., New York and Germany), individuals worldwide can purchase and use these services without the involvement of a healthcare provider.

With the list of DTC providers growing rapidly, it can be difficult to keep track of everything that is out there. At present, the only publicly accessible registries of DTC providers are maintained by private entities, including AccessDNA, DNA Test Index, and the Genetics & Public Policy Center (pdf) at Johns Hopkins University.

Recently, however, the NIH launched a new genetic testing registry (GTR) which has the potential to serve as a more comprehensive resource for tracking DTC genomics services. The GTR, which will include providers of both clinical and consumer personal genomics services, is not yet operational. Listing in the GTR is also voluntary so, even once it is in place, it is unlikely to serve as a comprehensive directory of all consumer personal genomics services. There are reports, however, that Representative Patrick Kennedy is attempting to revive the Genomics and Personalized Medicine Act in a form that would include a mandatory genetic testing registry.

Of all of the personal genomics categories listed here, consumer services is the one most likely to rapidly splinter into multiple categories. At the moment, there are few regulations that deal directly with DTC genomics companies and the services they provide. As the generation of genomic data becomes increasingly inexpensive and commonplace, the spectrum of consumer services will expand considerably. As was true of the development of personal genomic research norms, regulatory activity in this area has lagged commercial and scientific development. At some point, however, additional regulations will arrive, helping to further define this category. For instance, it is possible that the GTR will serve as a precursor to a more comprehensive system of regulation for genetic testing. Additional regulation, whatever its impetus, would likely produce further fragmentation within this category, with some companies sliding into defined regulatory boxes and others changing their offerings to avoid regulatory control (and expense).

Predicting precisely which consumer services will be offered and how, if at all, they will be regulated, is impossible. All we know is that personal genomics consumers ten years from now are certain to have many, many more options than they do today.

Unintended. This final category is a catch-all, characterized by a single shared feature: these individuals did not intentionally confront their personal genomic information. At the Genomics Law Report, we have discussed a variety of ways in which an individual might receive an unintended, and possibly unwanted, introduction to personal genomics. Paternity identification, surreptitious testing, genetic testing of a first-degree relative, forensic activity and the re-identification of previously de-identified genetic information all have the capacity to introduce unsuspecting individuals to their genetic information. It’s also possible that individuals who have agreed to share or to explore only certain aspects of their genetic information will be unexpectedly presented with personalized genetic information beyond the originally intended scope of their agreement. No doubt there are other means of unintended exposure as well.

While not every unintended exposure to personal genomic information will be undesirable, such occurrences should clearly be minimized. Although the GET Conference featured a self-selecting audience largely enamored of personal genomics, not every individual shares the desire to peer deeply, or at all, into his or her own genome. An introduction to personal genomics, no matter the context, should be expected, if not always desired (e.g., certain clinical testing), with ample opportunity afforded for pre-test education and, where necessary, informed consent.

Unfortunately, as the cost of generating individualized genomic data declines, more and more such data will be generated. The proliferation of personal genomic data, and the increasing array of valuable applications of such data, is likely to increase the incidence of unintended personal genomics exposures. A combination of public education and policy and legal reforms will be needed to minimize the number of such events and mitigate their impact when they invariably occur.

The Future of Personal Genomics. The categories described above are roughly drawn, and they may well be incomplete. There is no question that they are neither exclusive nor exhaustive. All we really know is this: to the extent that they accurately reflect the current personal genomics landscape, they will not do so for long.

Genomic researchers with novel questions will continue to require novel, and increasingly participatory, research models. Clinical practice will grow and is likely to become simultaneously more specialized (e.g., increasing availability of genetic diagnostic tests) and more generalized (e.g., incorporation of whole-genome sequences into medical records as a default). Consumer personal genomics will go wherever the entrepreneurial imagination can take it and regulatory bodies permit it, leading to splintering and further blurring between its boundaries with other categories.

The 2010 GET Conference closed with the personal genomics company Knome awarding a free exome sequence to the most original audience-supplied idea applying personal genomics. The winning proposal, submitted by Jonathan Eisen, would supplement understanding of our ancestors by sequencing current and ancestral microbiomes. A sampling of the submissions that didn’t win – including sequencing of millions of sperm from an individual to understand germ line variation, replacing newborn blood-spot testing with genomic sequencing, using real-time genetic testing to identify and prevent allergic reactions, constructing encryption keys from an individual’s genomic code and the development of new commercial models to expand access to and participation in personal genomics – provides a glimpse at the untapped applications for personal genomics.

Where will personal genomics head from here? I, for one, am already looking forward to the 2011 version of the GET Conference by which time, if recent history is any guide, this roadmap will already be out of date. And that, without question, is the most exciting thing about personal genomics as we close the book on the 2010 GET Conference.

In the meantime, if you missed the conference, there was plenty of live Twitter coverage. Everything I tweeted from @genomicslawyer can be found below, and there’s much more at the #GET2010 twitter notebook. Thank you to all those who helped cover the conference online, including GET Conference pioneers (Rosalynn Gill, Misha Angrist), moderators (Carl Zimmer, David Dobbs, Dana Waring Bateman), journalists (Edward Winstead, Emily Singer, Kevin Davies, Aaron Rowe), sponsors (Priscilla Oppenheimer), exome sequence winners (Jonathan Eisen) and many, many more.

Now for Genomes, Environments and Traits in 140 character snips:

• And with that #GET2010 draws to a close (except for the cocktails). Thanks to everyone that joined us in person and remotely.
• #GET2010 voting on the winning exome sequencing right now…and the winner is @phylogenomics !
• Conde: showing demo of the @Knome consumer browser. Very slick interface, though it comes w/ hefty price tag #GET2010
• Conde: have come a long way from when they launched (at a price of $350K / sequence). Trying to build Rosetta Stone for genomics #GET2010
• Final piece of #GET2010: Jorge Conde of @Knome is giving away a free exome sequence. Winning idea to be selected by audience via live vote
• Detailed coverage of Ion Torrent winners at #GET2010 from @bioitworld: http://bit.ly/c1SuzZ
• First Ion Torrent winner: John Iafrate, Long Le from Mass Gen. Second winner: Mitchell Sogin from MBL at Woods Hole. #GET2010
• Rothberg: giving away machines for cancer, safe water research. Goal is to democratize sequencing in the same way as computing #GET2010
• Ion Torrent actually giving away a pair of machines at #GET2010. One for cancer sequencing in clinic, one for safe water detection
• Jonathan Rothberg, Ion Torrent: describing the machine he’s about to give away. “Watson meets Moore” #GET2010
• Wrapping up a great #GET2010 conference. Awards presentations from Ion Torrent and @Knome. Will have live voting for exome seq coming up
• Enriquez: areas (e.g., Singapore) may not succeed if they are unwilling to tolerate difficult ppl. You need the right climate #GET2010
• Enriquez: moving from reading to copying to understanding to writing life code. And that will be a big deal when we get there #GET2010
• Enriquez: little labs that an build bridges will generate large economies. That’s how we move economy, healthcare forward #GET2010
• Enriquez: one difficulty is scientists who continue to focus on research, not the bridges to commerce #GET2010
• Enriquez: describes Harvard as a “desert of an ecosystem,” especially in comparison to MIT, Stanford, etc. Why is this? #GET2010
• Enriquez: why are certain places (MIT) so good at building this bridge, while others (Harvard, except HMS) are so lousy? #GET2010
• Enriquez: we need to grow the economy, which means we need to build a bridge to commercialize these technologies #GET2010
• Enriquez: genomics data is becoming so massive that it is beginning to drive large-scale industries (e.g., IBM, Intel development) #GET2010
• Enriquez: big companies – GE, Dupont, etc. – are leveraging this data. This is not all little startups #GET2010
• Enriquez: the growth here is spreading way beyond pharma, the way IT eventually mushroomed outward #GET2010
• Enriquez: if I was going to be investing in 10-15 years, I’d want to be focusing on the brain today. Will be big generator of cos #GET2010
• Enriquez: we now have single labs (eg Church) generating economies equivalent to small countries. This transition is disruptive #GET2010
• Enriquez: going to require exascale computing to manage data on this scale + ability to generate data surpassing ability to store #GET2010
• Enriquez: first zettabyte of data was generated by human species in 2009. Thinks single hospital will deal with that in 5-6 years #GET2010
• Enriquez: moved from human genome project (bounded in size, 3 billion bases) to an unbounded project: G+E+T. Much more complex #GET2010
• Enriquez: points out that the composition of meetings like #GET2010 is changing. Seeing ppl, companies we weren’t seeing 2-3 years ago.
• Final Prototypes of the Future speaker is Juan Enriquez of Excel Ventures: “Bridges to Commerce and Other Dirty Words” #GET2010
• Q: have you looked for discrepancies b/w 23andMe, Illumina data? West: happy with error rate of @23andMe #GET2010
• West: we remain optimistic about risk/reward trade-off, and value the family’s role as genomic pioneers #GET2010
• West: data analysis for family has only just begun, but already seeing medically actionable data, sense of relief w/in family #GET2010
• West: “this brings a sense of reality to what I’m learning in 11th grade AP biology”. Also notes need for bioinformatics in school #GET2010
• West: lists as her final next step: “Finish 11th grade” (to a roomful of applause) #GET2010
• West: next steps with this information? Needs some software (other than Excel) to speed up the analysis. Wants to pursue Factor V #GET2010
• No kidding RT @MishaAngrist: this kid is talking about meiotic recombination in her family…she is a genome hacker extraordinaire #GET2010
• West: now turns to sequencing. What data will that provide that genotyping didn’t? Describes process, consent to data #GET2010
• West: used raw data download feature from @23andMe. Huge dataset across family, analysis conducted in Excel #GET2010
• West: decided to use family genotype data to examine compound heterozygosity for DVT. #GET2010 (What qs were you asking at 17?)
• West: deep vein thrombosis as ex; diagnosis enables direct treatment, reduces risk. But not straightforward to measure. #GET2010
• Agreed. RT @phylogenomics: Anne West, high school student at #GET2010, is remarkably polished presenting before nobel winners, CEOs, etc
• West: starts by reviewing her family’s medical background. history of Alzheimer’s, heart disease, cancer, diabetes, etc. #GET2010
• Now up, Anne West (Harker High School) discussing her family’s whole genome sequencing (Illumina) / genotyping (23andMe) #GET2010
• Lincoln: need quality samples to get meaningful results. Low quality tumor samples = low quality results. Garbage in, Garbage Out #GET2010
• First q from @phylogenomics (from Twitter to #GET2010 floor). Unpublished genomes shouldn’t count. Lincoln agrees w/ need for public genomes
• Lincoln: challenges: determining what data means (interpretation), determining what data to keep (storage) #GET2010
• Lincoln: learned a lot about DNA sequencing, cranking out data. The bottleneck is finding high-quality samples & interpretation #GET2010
• Lincoln: will be “shocked” if don’t end 2010 with thousands of sequenced genomes. Thinks fully loaded cost (data+analysis) is $10K #GET2010
• Lincoln: accumulating lots of data that is not even being seen let alone interpreted Need quality, low-level algorithms to min data #GET2010
• Lincoln: humans don’t have just one genome: cancer is a disease of genomic changes. Sequencing of tumor-normal pairs important #GET2010
• Lincoln: now describing differences between exome / WGS sequencing, using Miller family as example #GET2010
• Lincoln: need to look to families, prospective parents, newborns, pre-natal, healthy individuals, clinical cohorts, etc. #GET2010
• Lincoln: this is good, but the numbers need to get much larger. Genomes need to come from variety of groups. #GET2010
• Lincoln: ended 2009 with 100-200 genomes deeply sequenced (not all published); CG did 60 or so alone #GET2010
• Lincoln: this type of story is now becoming much more common. Will continue to do so as WGS expands #GET2010
• Lincoln: sequencing changed the clinical resolution. Avoided liver transplant, changed diet instead. Infant recovered #GET2010
• Lincoln: describing case study of WGS for hypercholesterolemic infant; found putative cause after few days of data analysis #GET2010
• Lincoln: starts with discussion of what GWAS has/has not shown (rare vs. common variant point) #GET2010
• Now up, Steve Lincoln from @CompleteGenomic talking about an infrastructure for the future of human genome sequencing #GET2010
• Q : do you believe in probiotics? Knight: not a believer (at least for brand he studied), but evidence not yet published #GET2010
• Knight: it’s a bit like weeding a garden with a bulldozer and hoping what grows back is what you want. #GET2010
• Q: do you recommend using anti-bacterial soap for hand-washing? #GET2010
• Describing #BioWeatherMap, @tgoetz has a great analogy: we are the Earth, the microbes are the weather passing over us #GET2010
• Knight: goal is to expand from dollar bills (churches vs. strip clubs) to other surfaces (crosswalk buttons, schools, etc.) #GET2010
• Knight: #BioWeatherMap can be a keystone example of open-access, citizen driven science. Still needs support #GET2010
• Knight: finishes with a call to action for #BioWeatherMap. Broad-scale sampling across environments, integration w/ PGP data #GET2010
• Knight: conclusions? diff ppl, diff sites harbor diverse microbiota. Prospects for personalized medicine are excellent #GET2010
• Knight: looking at microbiota on dollar bills, comparing those collected from churches vs “adult establishments” #GET2010
• Knight: describing microbiota sampling 20 min after birth. Sharp contrast in communities based on birth type (c-section v natural) #GET2010
• Knight: showing changes in his own phenotype as well based on gut microbes. Lost 60 lbs after trip to Peru, antibiotic regimen #GET2010
• Knight: now describing how microbiomic communities produces different phenotypes in the host (mice obesity) #GET2010
• Knight: sampling microbiomes at 27 different body sites. “That’s a lot of different places to stick a q-tip” #GET2010
• Knight: research shows that very few microbial “species” are shared. Same results in human gut & human hands. #GET2010
• Knight: describing his open source data integration analysis pipeline (QIIME). Sequencing, barcoding, tree creation #GET2010
• Knight: is there a Wallace-esque biogeography line that separates microbial keyboard on our keyboard? Knight’s data says yes #GET2010
• Knight: return to Darwin. Recall that most life, and most biological evolution, is microbial #GET2010
• Knight: microbial abundance raises the question: how human are we? #GET2010
• Knight: phenotypes vary, but we are highly similar at genetic level. “You are not a beautiful, unique snowflake” #GET2010
• Knight: from Dawkins, van Leeuwenhoek to the Human Microbiome Project. We know there as many e.coli in your gut as ppl on earth #GET2010
• Now up at #GET2010, Rob Knight (Boulder) discussing the BioWeatherMap for microbial communities.: mapping what we are all exposed to
• Lipkin: next steps-sample prep, Dx & surveillance platforms, sequencing, bioinformatics, serology, gene-env-timing interactions #GET2010
• Lipkin: “it’s not the pathogen, per se, but the host-response” / genomics in isolation is not enough #GET2010
• Lipkin touching everything from Poe to cryptography to linguistic hierarchies, all in the name of virus ID. #GET2010
• IL’s description of his WHO work re: virus identification sounds like something straight out of Hollywood. #GET2010
• IL: now describing research investigating rapid, mysterious decline of bee population #GET2010
• IL: important not to focus on a single genetic/viral region; embrace entire microbial universe to understand how they cause disease #GET2010
• IL: showing examples of identification of novel disease-causing agents using genomic sequencing #GET2010
• IL: shows a tourism slide just prior to SARS: “Hong Kong: It will Take Your Breath Away” #GET2010
• Bit of misinformation RT @23andMe: @genomicslawyer @phylogenomics @dgmacarthur our SAB is still there, no changes to report #GET2010
• Back for the “Prototypes of the Future” sessions at #GET2010. Ian Lipkin (Columbia) now speaking about infectious disease
• Jim Watson, IP session: “I hate Myriad the way some people hate Goldman Sachs.” #GET2010
• That’s it for the #GET2010 breakout pitches. Now we disperse to learn, discuss. Back in a few hours for the afternoon sessions #GET2010
• TG: discussing the idea that genetics is information – like so many other types – and has the potential to help make better choices #GET2010
• Moderator & presenter @tgoetz from @Wired on Personal Health. How genetics illuminates the life path we take, the choices we make #GET2010
• DD: what are possibilities, problems as personal genomics produces info re: behavioral genes. How to understand, use that info? #GET2010
• Journalist @David_Dobbs on Predicting Temperament. Looking at recasting “risk genes” in a more nuanced light #GET2010
• RD: topics incl. how genetics changes nutrition, what we eat (and where), and what health benefits are available #GET2010
• Richard Delerins (French Chef, UCLA genetics researcher) on Nutrition & 21st Century Cuisine #GET2010
• JC: patents help display the always challenging intersection between law and science. Law lags behind, as usual #GET2010
• John Conley, RBH on IP: boils pitch down to 2 wrds: Myriad Genetics. How will Myriad, etc. impact development of personal genomics? #GET2010
• RP: new data suggests genotyping can reduce hospitalization due to drug dosage by 30%. How do we implement this in healthcare? #GET2010
• Ryan Phelan, DNA Direct on Genes & Drugs. Topic: translating actionable genomic info into the practice of medicine, today #GET2010
• DW: genetics can become more accessible. Question is what are best strategies to make genetics relevant, accessible? #GET2010
• Great idea for #GET2011 RT @andrewhessel, @phylogenomics $100 vs $1 metagenomes would be terrific. Would help with funding too! #GET2010
• Dana Waring, Personal Genetics Education Project on Education. Preparing next generation for intro of genetics into daily life #GET2010
• Jason Bobe (PGP) on DIY Genomics. If you like DTC genomics, you’ll love DIY. If you hate DTC, you’ll hate DIY even more #GET2010
• PR: topics for discussion: ID recessive risk alleles, prenatal diagnosis, newborn screening, PGx, etc. #GET2010
• Philip Reilly, Third Rock Ventures on Disease. Remember: 1/6 of world’s ppl does not have access to clean water. How do we improve? #GET2010
• GI: going to be describing #BioWeatherMap, microbiomic sequencing of dollar bills #GET2010
• Gerard Irzyk, Roche/454 on Desktop Sequencing & Analysis. Looking for feedback on how to make sequencing available to more ppl #GET2010
• JT: investigating how genetics gives a better picture of the consumer, and how it will lead to novel consumer products #GET2010
• JT: why consumer genetics? Cos like P&G are inherently involved in manipulating biology at individual level #GET2010
• (Won’t be able to live-tweet the breakout sessions; 10 happening simultaneously. Incentive to come in person to #GET2011)
• Getting started w/ the afternoon at #GET2010. Breakout session “pitches” are beginning, starting with Jay Tiesman, P&G on Consumer Products
• That’s it for the morning session from #GET2010. Tweeting will be lighter in the afternoon during the breakout sessions.
• Maxey: points out that genotype-phenotype associations require vastly improving our ability to describe, record phenotypes #GET2010
• West: doesn’t think it’s a bad thing if people have patents and want to charge for it. If I could get a medical benefit I’d pay #GET2010
• Church: discusses Myriad: whoever wins the court battle, the larger battle is being won by technology obviating (certain) patents #GET2010
• Q: about genome sequencing and patent infringement (curious to see what the panel will say) #GET2010
• Church (going back to Bob Green’s comment), agrees that there needs to be constant reevaluation of info based on outcomes #GET2010
• Q: how will culture change through personal genomes? Will it be like private investigators being replaced by Google searching? #GET2010
• Green: we need ways to stratify information, determine what is useful vs. not useful. #GET2010
• Green: not all information is necessary beneficial to human health. Concerned about raiding of the medical commons #GET2010
• Bob Green: science of discovery vs. science of disclosure, linked by science of health outcomes. #GET2010
• West: wishes his MD would take advantage of looking at his genome. It’s only become more complicated. #GET2010
• John West: methylation is an important, natural extension of the technology. Will be part of rich datasets necessary to advance #GET2010
• Q: what about the third leg? In mice, e.g., we can control environment and genome. What about epigenetics? #GET2010
• JW: interpretation will not scale unless there is automation. Focusing on educating doctors the traditional way will not work #GET2010
• John West: Edu is important but inconceivable that doctors will all become genetic experts. Automated interpretation is needed #GET2010
• Lucier: this is a huge concern. Sponsoring MD certification program (Topol), MD training fellowships. Will do more… #GET2010
• Q: what needs to be done to help medical profession catch up to where the technology is? #GET2010
• Anne West: considers sequencing/genotyping an investment that pays off over time #GET2010
• Audience q: how do we know sequencing is safe? GC: we don’t, and shouldn’t rush into. Early adopters take some of the body blows #GET2010
• GC: (response to question) – some data will be compromised, but the more sharing that takes place the better #GET2010
• Krulwich wrapping up the panel with a quote from Barney (and lots of laughter). I think you needed to be here for that one #GET2010
• Church: don’t need to look 10-20 years ahead. It’s what is already available – or was avail 2 years ago – that we should talk about #GET2010
• Church: think of genome sequence as a cell phone (play and explore) but also as an insurance policy. Risk info you hope not to need #GET2010
• Church: this is going to penetrate more broadly w/ time. May not be a single tipping point. #GET2010
• Church: thinks this has already happened, even if we don’t notice. ~1800 medically actionable genes, held by 10% of pop’n #GET2010
• Q: what will be the discovery / development that will make personal genomic sequencing a societal, medical imperative? #GET2010
• Church/Lucier: sees adoption of EHRs as a separate issue. Sequencing is fundamentally digital, will develop along parallel path #GET2010
• Q from @carlzimmer: is healthcare ready for personal genomes? Can you drop that data into a patient’s traditional medical record? #GET2010
• Lucier: understanding genomes is fundamental to science, & a viable biz. There are many applications beyond what we’ve discussed #GET2010
• Krulwich: sees personal genomes as a slog – through public acceptance, privacy issues, science, etc. Why is this perception wrong? #GET2010
• West: preventative medicine fundamentally lowers costs, improves outcomes. #GET2010
• Q: are we going to just be generating needless medical workups, tests, etc. Will we overburden doctors? #GET2010
• John West: don’t sequence to find out about diseases we already knew we have. Learning new information that is actionable #GET2010
• Wests: MD didn’t find anything, but now they can monitor over time and detect – and treat – at early stage. Ex of why to sequence #GET2010
• Wests: talking about “exfoliation glaucoma”. No reason to suspect risk of this, but learned it from genotyping. Went to see MD #GET2010
• Changing the panel one last time: back on stage: George Church, Anne and John West, Greg Lucier #GET2010
• Gill: enthusiasm (& investment) created technologies, progress we could have never imagined. So there is reason for excitement #GET2010
• Dyson: discussing @23andMe SAB, and how attitudes changed (opened) about what data could be returned #GET2010
• Dyson: scientific progress proceeds one funeral/investigator at a time. Getting the public engaged speeds this #GET2010
• Lupski: science is hard; anybody who doesn’t think that is fooling themselves. Will take time to separate signal from noise #GET2010
• Q for panel: “is there a disconnect between enthusiasm at #GET2010 and how complicated/hard this is?”
• Kim: has also sequenced wife and two kids as well. Interested in whether kids share the same genetics risks he does #GET2010
• Kim: based on genotype, phenotype data (temporary vision loss) he is taking preemptive steps to try to address risks #GET2010
• Seong Jim-Kim now talking about learning of his own risk for macular degeneration, usefulness of his own sequence #GET2010
• Lupski as Columbo for genetics. Moving from SNPs to gene panels, and soon will simply do whole-genome once #GET2010
• Lupski: we’ve learned an incredible amount over the past years. It’s not all in the base pairs. We need sequencing #GET2010
• Lupski: now discussing his exp (and that of his family) w/ Charcot-Marie-Tooth disease #GET2010
• Lupski: as MDs, we should not be paternalistic & control what info ppl can have access to. Should instead tell them what it means #GET2010
• Flatley: we have abstracted those in a way that creates actionable information; we need to do the same for whole-genome sequences #GET2010
• Flatley: remember that genetic tests are done every day; in most cases neither MD nor patient understands underlying technology #GET2010
• Lupski: but complications, fear, should not stop us from learning (and he is most interested in medically actionable variants) #GET2010
• Lupski: it is hard. We don’t understand function of 90-95% of human genes. That is humbling #GET2010
• Angrist: if we focus solely on individual understanding/value we lose sight of the value this contributes to science #GET2010
• Q: are the stories our genes tell us simply too hard for (some) individuals to understand? #GET2010
• Gill: emphasizing that understanding neither starts nor stops at the genome. You have to focus on environmental components as well #GET2010
• Dyson: we are helping people understand their own genetics. If they can understand the Red Sox, they can understand @23andMe #GET2010
• Dyson: it will take a long time to understand personal genomes. So there is value in starting now #GET2010
• Dyson: thinks MDs are good when you need them. But shouldn’t be required for ppl to look at their own data. #GET2010
• Flatley: philosophically agree that no MD should be necessary, but thinks involving one is most robust regulatory / safety approach #GET2010
• Flatley: my MD refused to write a prescription for full genome sequence (required by $ILMN) b/c he knew nothing about it #GET2010
• Lupski: says @23andMe just disbanded their scientific advisory board? (Did I hear that correctly?) #GET2010
• Dyson: “Can’t talk to god yourself; you need a priest. But we are heretical, just like Gutenberg” #GET2010
• Dyson: @23andMe also received letters from states, and adapted to comply. States like MDs as gatekeepers. #GET2010
• Dyson: @23andMe has a slightly different story, but the same basic issues exist. Give information, not advice #GET2010
• Gill: received cease & desist letters from CA, NY and MD. Thought regulations didn’t apply; regulators didn’t. Uncertainty is tough #GET2010
• Gill: challenge Sciona ran into was access to capital, not regulatory hurdles. But we need is greater clarity in what is allowed #GET2010
• Panelists, including Gill and Dyson now being asked about regulatory enforcement / hurdles. Are they worried about this? #GET2010
• Flatley: still trying to get the iPad app right internally. Plenty of underlying issues, but this is where we see the future #GET2010
• Flatley: have ported application from iPhone to iPad. Allows sharing of genome with MD, pharmacist, family, etc. App still internal #GET2010
• Krulwich asking Flatley about his prototype Illumina iPhone app. Is instantaneous analysis the future? #GET2010
• Transition now from the burdens of genomic sequencing to the benefits – for individuals, as well as the cos, investors #GET2010
• Stepping down: Maxey and Gates. Coming back up: Flatley, Gill, Jim Lupski, @MishaAngrist, @edyson, Seong Jim-Kim #GET2010
• Maxey: not all donors want to be found; but that’s a minority. Most find it a great experience to reconnect w/ donor-conceived kids #GET2010
• Maxey: no reason/value for denying ppl access to their genetic information, including sperm donor children seeking to locate him #GET2010
• Maxey: my identification was made much easier by being in the PGP (participant #5); Maxey understood and was in favor of this #GET2010
• Maxey: donated sperm numerous times in the 80; years later he was located by his children. It was a “wonderful day” #GET2010
• (For background on Maxey’s story, see this Newsweek feature: http://bit.ly/4Dh5aO #GET2010)
• Gates handing it over to Kirk Maxey to talk about re-identification with genetic information (in the form of sperm donation) #GET2010
• Gates: there are cultural diffs, but everyone shares the impulse to understand one’s ancestors. Just need to tie in genetics #GET2010
• Gates: the world values genealogy (aside: Mormons are “the Borg of genealogy – eat up all the records we can find”) #GET2010
• Q: is this a peculiarly American set of values? Would the same story resonate in France or in China? #GET2010
• Gates: this allows us to see ourselves as a genetic bouillabaisse, which is what we are. A new measure of identity #GET2010
• Gates: this was the first time he ever saw white people be disappointed that they didn’t have white ancestry #GET2010
• Krulwich: this is a celebration of “mutt-dom” that is fantastic. Gates: yes, and people don’t mind!” #GET2010
• Gates: expected emotional peak to be genetic ancestry; instead it was locating genetic relatives by name That made it relevant #GET2010
• Gates: has had to raise $21M for his various genealogy secrets. Now describing how he landed Oprah #GET2010
• (Skip Gates has landed at least one joke every 90 seconds on stage. Playing the crowd at #GET2010 even better than Jim Watson)
• Gates: you get greater breadth and depth of information. Helps tell the larger identity narrative #GET2010
• Q: is whole-genome sequencing important for genealogy? Does it add much that genotyping, Y DNA, mtDNA doesn’t? #GET2010
• Gates: it is tough to get informed consent. Considers himself reasonably informed, but took him a long time. #GET2010
• Gates: that was irresponsible science. They should have been asked, provided informed consent. Admires PGP model #GET2010
• Q: what happens when the story that is shared isn’t one that you want to hear (e.g., Havasupai Indian) example? #GET2010
• Gates: comparing genealogy to photography. Both are representations. We need to learn how to read a genome way we read a photograph #GET2010
• Gates: just a bunch of bands and colors, but it was a tremendously emotional moment. “Like my mother coming back from the grave” #GET2010
• Gates: first father-son to have genome fully sequenced, as well as first African-Americans #GET2010
• Gates: every day his brother calls, he worries his dad has died. Wanted to immortalize his father and make the genome public #GET2010
• Gates: high point of Faces of America was showing unexpected relatedness to the guests. Putting faces, timelines to haplotype grps #GET2010
• Gates: describing how he put together Faces of America: took the Noah approach to genealogy – 2 from each background #GET2010
• Break over. Now on stage, Skip Gates (PGP#12) and Kirk Maxey (PGP#15) talking about tracing relatives through genetics #GET2010
• Quake: qualifies that anybody with employer-sponsored healthcare will have $0 cost. Dyson points out that isn’t everybody. #GET2010
• Dyson: disagrees. Nothing is cost-free. Who is investing, and what is returned on that investment. #GET2010
• Quake: the cost is $0, George is right. Thinks not just sequencing, but also interpretation will go to $0 as well. #GET2010
• Dyson (in response to question of whether $99 is good enough, why pay $48K): in 2-3 years we won’t do SNPs. “Why bother?” #GET2010
• Flatley who will have access? Goal is to make it integrated part of healthcare (eg every child born is seq). Still 10 years away #GET2010
• Flatley: we need 100s, 1000s of genomes in a single place. We’re still ramping up to that. Need to sequence first. #GET2010
• Quake, on speed of sequencing. Quick to knock out raw data (2 wks; 3 authors), clinical annotation is hard (20 authors, 1 yr) #GET2010
• Dyson: we are very careful not to call this a “medical service” since that is regulated #GET2010
• Dyson: @23andMe will be offering a whole genome sequencing service “some day,” but ancillary services will remain critical #GET2010
• Dyson: more than pure sequencing (eg what @23andMe is doing) is important to consumers; saw a “huge response” to DNA Day $99 sale #GET2010
• Flatley: if the price drops to $0, as Church says, then we have a problem #GET2010
• Flatley: thinks the market is “incredibly elastic”; concerns about commoditization, but volume will expand rapidly #GET2010
• Dyson: one reason Chinese market is growing is that they are not as worried about the ethical / privacy issues #GET2010
• Watson back on stage to talk about collaboration between Cold Spring Harbor & China #GET2010 Still believes US is better at technology
• Flatley: bioinformatics means: storage of data, sequence alignment, interpretation of data. Need all 3 to have something meaningful #GET2010
• Dyson: China is becoming the dominant market. Flatley: we have one customer who will be end of year have capacity of entire US #GET2010
• Flatley: bioinformatics, sample prep are becoming the dominant component of cost #GET2010
• Flatley, Quake, Dyson and Seong-Jim Kim discussing price of sequencing #GET2010
• (Apologies for temporary darkness. Twitter thinks I’m a robot – too many tweets from #GET2010)
• Anne West: not planning to publish her own data, possibly at 21, probably not until later. Her brother also keeping data private #GET2010
• JW: Anne will be talking this afternoon about what the family has learned, but first lesson is data is complicated; takes time #GET2010
• JW: in our family, the information is medically actionable today #GET2010
• JW: talking about the risks of sequencing, but what about the risks of NOT sequencing; not having access to actionable information #GET2010
• John West: he’s not sick, but he’s still at risk (embolism as an example). #GET2010
• John West: first point: why are we talking about risks of genome sequencing when @edyson is talking about being shot into space? #GET2010
• AW: first genotyped by @23andMe, which led to Illumina sequencing. Prompted by father’s embolism. Treatable, but need to know. #GET2010
• AW: thinks what is acceptable to talk about publicly changes with generations, although it’s not as if there are no distinctions #GET2010
• Anne West talking about the Facebook generation’s privacy preferences #GET2010 AW thinks her generation is much more open, public
• Angrist: if genomic science has taught us anything, it is that this information is not powerfully predictive #GET2010
• Angrist: helps that daughters will only receive probabilistic knowledge (mother’s genome not public) #GET2010
• Angrist: tries not to think about the fact that, in time, new knowledge will crop up. Daughters will learn plenty from the internet #GET2010
• Angrist: biggest concern was daughters were finding out they were at risk from the internet; wanted them to find out from parents #GET2010
• Angrist: daughters are aware of the PGP (recommends “Here Comes Science” by They Might Be Giants for explaining DNA to kids) #GET2010
• Angrist: was pre-tested for BRCA1/2 common mutations. Once those came back clean, his greatest fear was removed #GET2010
• Angrist: his concern was BRCA status, given family history and his two daughters. Long family discussion before joining PGP #GET2010
• RK: What about “the Cassandra problem”: learning something about future development of children that perhaps should not be known? #GET2010
• Now coming on stage at #GET2010, @MishaAngrist, John West and Anne West #GET2010 to talk about sequencing and families
• Flatley: makes a point that genomic sequencing is like credit cards online: uncomfortable at first, but pros outweigh the cons #GET2010
• Flatley: worrying about theoretical bad things is understandable, but need to tip the balance so costs outweigh the cons #GET2010
• Dyson: disease is clearly important. But seemingly frivolous things (eg genealogy) are important to the growth of the field #GET2010
• Lucier: focus of why people should get sequenced is to solve disease. Not to dismiss consumer aspects, but priority to disease #GET2010
• RT @tgoetz: Fwiw I’m on @npr’s here&now today w @edyson talking DNA & health. Natl showtimes here: http://bit.ly/bJ445q #GET2010
• RK: what about identifying which parent supplies certain alleles/traits? Has this created any interest among marriage counselors? #GET2010
• GC: we encourage family enthusiasm and discussion around participation in the PGP #GET2010
• RK: what about if you have a twin and they disagree? GC: PGP policy is that identical twins cannot join unless both join #GET2010
• TW: became concerned once she became a mother. Thinks her daughter should make the decision for herself. GC went ahead, TW did not #GET2010
• TW: their family treats sequencing as a matter of personal choice. Describing her own reservations about publishing her own seq #GET2010
• Ting Wu (George Church’s wife) talking about how genomic sequencing has been discussed in their family. #GET2010
• RG: raising awareness of the value of DNA as information is important. “guess what, it didn’t kill me to find out about my DNA” #GET2010
• RG: my family is very intellectually curious. Not concerned about publishing genome. If it helps raise awareness, that’s worthwhile #GET2010
• Rosalynn Gill: “knowledge is power…I want to know all of the information, and the same for my family.” #GET2010
• ED: Not worried sharing her genome. “I’m 58, I’m not dead yet. Will die of something, but total risk of dying cannot exceed 100%” #GET2010
• ED: thinks the legal restriction against insurers using genomes (GINA) is a problem, because it prevents lowering treatment costs #GET2010
• ED: training to be a Russian cosmonaut. Had to have her health insurance notarized, but they had no interest in seeing her genome #GET2010
• Esther Dyson: PGP#3 and early adopter of @23andMe. Invited her whole family, never occurred to her that they wouldn’t be interested #GET2010
• Now coming up on stage: Esther Dyson, Rosalynn Gill, George Church & Ting Wu #GET2010
• JF: biggest argument against sequencing was implications for children. But it is a personal choice (Flatley’s wife not interested) #GET2010
• JF: similarly unconcerned about privacy issues. For me, sequencing was really not a question. #GET2010
• GL: thinks the privacy issues will simply be handled. Wants to lead by example for personal genomics #GET2010
• GL: for his family, because of his biz, this has become a very familiar conversation. Sequencing the family is “next logical step” #GET2010
• JF & GL: both discussed with their families, and not with their boards of directors #GET2010 Lucier going to sequence his whole family nxt
• Q: should an executive of a multi-billion dollar company publish their genome? #GET2010 Flatley’s is up, Lucier’s is coming up soon
• Watson stepping down. Now on stage at #GET2010: Jay Flatley and Greg Lucier to talk about biz of genomics
• JW: limiting factor at this point is intelligence of scientists, not $. Encourage ppl to put genomes online (“send them a pie…”) #GET2010
• JW: the ethical objections to genomic sequencing are just “crap” – a minor blip on the radar screen #GET2010
• JW: “I am very happy that we can do it. Don’t have to talk about $. Just whether humans are bright enough to get its act together.” #GET2010
• Q for Watson: are you amazed that we are now at a point that we can do intimate investigations of an individual’s inheritance? #GET2010
• JW: thinks PGD will be very important in the future (e.g., for bi-polar disease) People will have diff opinions re: nasty traits #GET2010
• Q: is lowering the price of genomic sequencing enough? JW: it should be. Immoral not to pursue it #GET2010
• JW: the argument for sequencing is the same as for motherhood: why wouldn’t you just do it? #GET2010
• JW: we should sequence 100,000 genomes. Cost will be nothing, interpretation will be everything. Goal is to find pathways #GET2010
• RK: does sequencing complicate parenthood? JW: why should it? It’s an absurd sentence. It’s just genetics #GET2010
• What did he learn? JW: lactose intolerance, cytochrome P450 (which changed my beta-blocker medication). That was very useful #GET2010
• JW: “I didn’t think about sequencing because I have other things to think about” #GET2010
• JW: lack of concern reflects his age. At 20 he would have worried. At 80, what is there to worry about? #GET2010
• JW: at this stage of my life, I tend to say yes. Willing to be sequenced (other than APOE)(and we know how that worked out) #GET2010
• Jim Watson now up on stage #GET2010, sandwiched between CZ and RK. Why did Watson decide to be sequenced? “JW: I don’t remember”
• Now up at #GET2010: Robert Krulwich and @carlzimmer leading the genomics pioneers session. No idea what to expect…
• GC: PGP is not a monopoly, not the sole model. It is intended to inspire creativity, help us move forward #GET2010
• GC: some subset of us must share genomes + environment + traits in order to really understand, test deep connections #GET2010
• immune-ome does not escape a #badomics award RT @phylogenomics: @genomicslawyer not approved not approved #GET2010
• GC: personal genome -> traits, with stops in between: epigenome, microbiome, immune-ome, etc. #GET2010
• GC: what else can you examine? “immune-ome” (@phylogenomics approved?) using 454/Roche sequencing. Looking at vaccination response #GET2010
• GC: what else can you do with PGP / open communities? Collaborating w/ fMRI researchers to examine PGP population #GET2010
• GC: what about epigenetics? PGP collects tissue, creates iPS lines to reprogram to any tissue. Showing published data #GET2010
• GC: “which traits to focus on?” Many ways to conceptualize. Not everything must be life-threatening to be important #GET2010
• GC: oldest PGP volunteer is PGP #11 – Skip Gates, Sr. Demonstrating allele identification, interpretation tool #GET2010
• GC: if we act as a community, we can improve genomic interpretation. http://evidence.personalgenomes.org #GET2010
• GC: “how many complete genomes are there?” (Putting aside the missing 7%), probably around 17 #GET2010
• GC: now discussing specifics of PGP. For more visit personalgenomes.org #GET2010
• GC: even if you can encrypt data, controlling access to the material itself is difficult #GET2010
• GC: on re-identification: we can promise privacy, but that would be disingenuous. And what about cell lines? #GET2010
• GC: “Who to sequence?” Need to embrace non-experts. Families are the best non-experts to embrace. Amazing what you can from family #GET2010
• GC: “Why public GET datasets?” Remove barriers to research & serendipity. We want to encourage imagination. #GET2010
• GC: “What if there is no cure? Do we not want to know?” GC wants to know. Inspired by Odone, Fox, Rienhoff, Heywood, Melton, etc. #GET2010
• GC: Genetests: 1770 genes: highly predictive & medically actionable. Why don’t they show up in DTC tests? #GET2010
• GC: “Are rare diseases so rare?” Add them up and 10% of us have a rare disease, and more are carriers #GET2010
• GC: “Should we cure genetic diversity?” Tricky question comes with trade-offs. Depends on the gene in question. #GET2010
• GC: “what if the gov’t started testing babies for intelligence genes?” This already happens: PKU #GET2010
• GC: #GET2010 more than just cheerleading. Imagine the unintended consequences of personal genomes – positive & negative
• GC: $0 genome comes w/ strings: ex: data sharing. What are other ways that the cost will be covered? Inspect your genome’s label #GET2010
• GC: the endpoint is the $0 genome. Cost somebody something, but costs the individual nothing. #GET2010
• GC: “who is my choice for the seq technology winner?” Answer: “yes” (Puts up a list of 20 companies) #GET2010
• GC: over 200M base pairs still missing – that’s a huge gap. #GET2010
• GC: “mission accomplished…except 7%” We haven’t finished a single human genome yet. E.g, 20M base pairs missing on chromosome 1 #GET2010
• GC: history of DNA Day from 1953 to 2010. Focus on DNA structure, HGP and GINA. Interesting to see GINA elevated to that level #GET2010
• GC: beginning with a Q&A of himself. First question: when is the next personal genomes meeting? #GET2010
• And we’re off at #GET2010. George Church delivering intro keynote. Starts with a slide of nudibranchs…
• #GET2010 getting ready to begin. Agenda here: http://bit.ly/anBDd6 Morning will be free-flowing convo w/ genomic pioneers

The research began two decades ago, ostensibly to search for a genetic variant that might be contributing to the increasing rate of diabetes in the tribe. The diabetes research proved unfruitful, but the blood donated by the Havasupai tribe members, and the DNA extracted from it, led to a number of follow-on research projects, grants and publications. It was that research – including searching tribe members’ DNA for variants linked to schizophrenia, and inferring the likely ancestral origins of the tribe’s founders – that led to lawsuits, millions in legal fees and, ultimately, the settlement.

Implications of the Havasupai Settlement. Harmon’s article provides a concise background to the dispute, and briefly describes the $700,000 settlement between ASU and the tribe to “remedy the wrong that was done.” Harmon and unnamed “legal experts” suggest that the settlement is significant because “it implied that the rights of research subjects can be violated when they are not fully informed about how their DNA might be used.”

In some respects, this is a trivial conclusion. One of the most important and well-known elements of the Common Rule – the regulatory regime that governs federally-funded human subjects research – is that researchers must seek, and participants provide, informed consent. Participants that are uninformed cannot provide valid consent and, thus, their rights as subjects are violated. In that respect, at least, the Havasupai case tells us nothing new. (I have not seen the settlement, but I doubt that it will (a) be made public or (b) contain an express admission of guilt from ASU, both factors that will limit its relevance to future similar scenarios.)

But the Havasupai case and Harmon’s article shine light on an important, and difficult, problem that continues to face scientific researchers, particularly those exploring human genetic variation: what does it really mean to provide “fully informed” consent for genomic research?

Fully Informed Consent? Looking at the text of the Common Rule, there are requirements that the researchers describe the nature and purposes of the research (§ 46.116(a)(1)), as well as both reasonably foreseeable (§ 46.116(a)(2)) and unforeseeable (§ 46.116(b)(1)) risks of participation. But the standard of informed consent that must be achieved is not explicitly spelled out. Is it “reasonably informed,” “substantially informed,” “fully informed” or something else altogether? (Interestingly enough, the language that Harmon uses – “fully informed” – does appear, but only in sections regarding research on pregnant women and fetuses, which is not applicable in this case.) Even if a clearer standard were articulated, how would researchers demonstrate that it had been satisfied?

The requirement of informed consent is part of the bedrock of modern human subjects research in the United States, and it is not going anywhere. In fact, the story of the Havasupai, as well as the tale of Henrietta Lacks (told so remarkably well in Rebecca Skloot’s new book) and other past failures of informed consent, suggest the informed consent requirement is here to stay, as well it should be.

A Difficult Balance. Yet, as we push forward into an era of large-scale, personalized genomic research, it is impossible to ignore the difficulties – legal, ethical and practical – that informed consent requirements impose. For example, truly informed consent for genomic research might require participants to possess a deep – or at least working – understanding of the underlying science. That sets a very high bar, and finding sufficient numbers of participants capable of providing such consent could restrict important research.

Even more daunting, however, is the difficulty of fully informing participants of the benefits and risks of participation in genomic research – particularly where the resultant findings could conceivably be linked back to the individual or, as in the case of the Havasupai, the individual’s community – when the researchers themselves lack this understanding. What genetic information can tell us about disease and other traits, and how this information can be used or misused in the case of individuals, is an area of continuing uncertainty. With the publication of the draft human genome sequence a decade in the rearview mirror, we know more than ever before. But there is still much that we don’t know.

Thankfully, new research models and strategies for seeking informed consent are being developed and tested. For instance, the Personal Genome Project (PGP) – for which I am an advisor, including with respect to the informed consent protocol – employs a model of “open consent.” The PGP focuses on preemptive and extensive risk disclosure, along with rigorous participant pre-screening to ensure that the risks of participation are understood. More broadly, the difficulties of informed consent and genomic research is an issue that the NIH is studying on an ongoing basis, with multiple internal working groups looking at different dimensions of the problem. Nevertheless, informed consent for genomic research poses a considerable challenge for policymakers, funding bodies, researchers and participants, and it is unlikely that any of the existing models represent a perfect approach.

None of this should be taken to mean that informed consent for genomic research is impossible. To admit that would leave us with the unenviable choice of sacrificing either the informed consent of participants or the valuable scientific research they enable. What the case of the Havasupai tribe does underscore, however, is just how difficult a task this is. It is clear that the next generation of personal genomics research will require more than purely scientific breakthroughs. We also need to think creatively about the ethical and legal framework in which such research is conducted, to make sure that it continues to promote scientific progress while protecting the participants – no matter what their background – that make such research possible.

As we’ve written earlier (“Back to the Future: NIH to Revisit Genomic Data-Sharing Policy”), the ability to link – and to share – genotype and phenotype data (including medical records, particularly treatment and outcome data) will be essential to the development of the next generation of genomic research. One of the most common ways to link genotype and phenotype data is to combine genomic data with electronic medical records (EMRs). A particular patient’s EMR may contain everything from basic biographical information to family medical history to current diagnoses, including ICD codes. When it comes to associating genes with medical conditions, researchers rely on International Classification of Disease (ICD) codes to categorize individual patients by disease type and search for shared genetic variations that might play a causal role.

Cracking the Codes. Obviously identifying information (e.g., biographical information) is generally required to be removed pursuant to HIPAA regulations. ICD codes, however, are sometimes retained for purposes of genetic association research and, in some circumstances, a set of otherwise anonymous ICD codes pulled from an EMR can be traced backwards to identify the specific individual supplying the codes.

The new research from Loukides et al., a team which includes data privacy pioneer Bradley Malin, recognizes the potential for genomic privacy risks created by linked genotype-phenotype datasets. Loukides and his colleagues propose a mechanism for modifying such datasets to eliminate one route to individual re-identification while retaining enough information to make the data useful. From the abstract:

This work proposes an approach that provably prevents this type of data linkage and furnishes a result that helps support GWAS. Our approach automatically extracts potentially linkable clinical features and modifies them in a way that they can no longer be used to link a genomic sequence to a small number of patients, while preserving the associations between genomic sequences and specific sets of clinical features corresponding to GWAS-related diseases. Extensive experiments with real patient data derived from the Vanderbilt’s University Medical Center verify that our approach generates data that eliminate the threat of individual reidentification, while supporting GWAS validation and clinical case analysis tasks.

The approach from Loukides et al. involves (i) designating individual-level medical data that are potentially identifiable (the ICD codes) and then (ii) modifying the data in such a way that they no longer pose a risk of re-identification. The team’s approach combines a privacy policy (determined by reference to the size of subsets that can be created using the ICD codes) with a utility policy (a set of diseases that can be categorized by combining various ICD codes without overly distorting the phenotypic information those codes represent) to construct a dataset that “provides provable protection from individual reidentification based on clinical features” while enabling important GWAS research.

A Balancing Act. The primary reason why genomic privacy even presents as an issue, of course, is that most individuals are uncomfortable publicly sharing their genomic and medical data. Although some “information altruists” agree to waive their privacy rights and participate in research projects – most notably the Personal Genome Project, which employs a fully public data release and consent model – most genomic research, and particularly research that combines genomic and other medical data, is premised upon some level of privacy for the participants.

The fundamental tension is how to balance individual desires for privacy with a collective interest in employing linked genotypic and phenotypic data to advance scientific understanding and, ultimately, provide improved medical care to individuals. Pure privacy – or sharing no data that could possibly be re-identified – is an untenable solution, because it is impossible. On the other hand, requiring participants to waive all privacy rights is equally untenable because it would, in all likelihood, dramatically restrict the available pool of research participants. (And, as The Wall Street Journal reported today, patients may lie to their doctors if they believe their EMRs will ultimately be shared without appropriate privacy protections, behavior that would hamper both research and medical care.)

Viewed in light of this ever-present tension, the model proposed by Loukides et al. should be applauded for its contribution to the continuing project of striving to balance the conflicting desires of robust individual data privacy and broad access to linked medical and genomic datasets. As Malin puts it: “Generating data is expensive, and it’s both good science and good etiquette to reuse data. The challenge is to do it while protecting people.”

By seeking to block a significant path to re-identification (even if it is impossible to eliminate all possible re-identification scenarios) while preserving the utility of the published data, the approach put forth by Loukides et al. can provide needed comfort to researchers, institutions and participants considering the publication of linked genotype-phenotype datasets. After all, simply because data might be identified does not mean that it need be easily identifiable, and in many research settings robust privacy protection mechanisms will continue to serve a critical function.

Teri Manolio, director of the Office of Population Genomics at the NHGRI, agrees that the team’s approach shows promise. “It does a good job of trying to maximize the information shared while minimizing the risk for re-identification, recognizing that these goals are in dynamic tension and both cannot be fully met at the same time.” Encouraging words from an agency that has struggled to strike the proper balance between privacy and access when it comes to genomic data.

One Kind of Re-Identification. Whether the Loukides method will be adopted remains to be seen, and a technical analysis of the algorithm is beyond the scope of this article. Either way, while the approach described by Loukides and his team – if validated – appears promising, it is important to emphasize that this particular privacy protection mechanism addresses only one pathway of genomic data re-identification. Even if the Loukides et al. method “eliminates the threat of individual reidentification” using statistical measures applied to certain linked genotype-phenotype datasets, researchers have recognized that re-identification can occur in a variety of ways.

As George Church pointed out, one of the most prevalent forms of re-identification occurs through accidental or intentional releases of data that were never intended to be public, such as the data breaches tracked by the Privacy Rights Clearinghouse. Such unintended data releases could, at least in theory, compromise otherwise secure datasets. Re-identification is thus unlikely to be a risk that is ever susceptible to complete elimination. (For a more complete discussion of this issue, see our previous post, “Re-Identification and its Discontents.”)

The Genomic Privacy Two-Step. Loukides and his colleagues recognize that they are providing only a partial solution, and note that genomic privacy tools such as theirs are only effective when applied in an appropriate fashion. As the authors point out, “as is true of all data anonymization methods, our approach leaves the decision of selecting a suitable privacy protection level…to data owners or policy officials.”

Furthermore, striking a sensible balance between privacy and access is only the first step in developing a responsible approach to privacy in genomic research. Researchers and institutions must also be sure to communicate the relevant trade-offs to those individuals whose data will be used in the research, to ensure that they understand – and agree with – whatever risk of identification has been deemed appropriate to the proposed research.

Tackling both prongs of genomic privacy – the risk of re-identification and accurate communication of that risk – is necessary to ensure that the next generation of genomic research is conducted in a way that is technically robust, as well as ethically, legally and socially responsible.