Genomic Sequencing
The Past, Present and Future of DTC Genetic Testing Regulation
[Editor’s Note: Newsweek science editor Mary Carmichael has a DNA Dilemma. As Carmichael debates whether to take a direct-to-consumer (DTC) genetic test, she is soliciting feedback from the DTC community, from the public and from other commentators, including myself. At the end of the week, she will make her decision.
On Tuesday, Carmichael and five commentators examined what can be learned from a DTC genetic test. Yesterday, the topic was whether DTC genetic tests are trustworthy, and whether the results can be cause for concern. Today’s topic is the regulation of DTC genetic tests. In addition to several short commentaries, including a much shorter version of the piece below, Carmichael has also posted a lengthy interview with two top FDA officials on the subject of DTC genetic testing regulation.
The column below is an expanded version of what appears over at Newsweek. To see all of the commentaries in Carmichael’s series, click here.]
The recent media attention focused on direct-to-consumer (DTC) genetic tests has left companies, investors, consumers and even regulators scrambling to figure out what comes next.
As the situation stands today, companies and their investors live in a climate of unprecedented regulatory uncertainty, causing delays in the introduction of new products and rendering an already inhospitable economic climate – for both fundraising and sales – even more challenging. Commentators and regulators caution consumers that some DTC genetic tests may be unreliable or, worse, harmful, but have yet to provide clear tools and guidelines for evaluating competing tests. And regulators, including the FDA, must balance their mandate to protect the health and safety of the public with that same public’s desire for autonomy, while also recognizing that innovation is a prerequisite for a healthcare system that must continue to improve outcomes while reducing costs.
Clearly, something must change. But what will that change be? And how will the field of DTC genetic testing evolve? Will DTC be able to continue its current business while regulators and companies engage in protracted negotiations? Will oversight weed out the “snake oil salesmen” and permit legitimate companies to flourish? Will it drive all genetic testing (temporarily) out of the hands of consumers?
Or will the field change in a dramatic and completely unexpected way?
“From Gulf Oil to Snake Oil”: Congress Takes Aim at DTC Genetic Testing
It has been a busy week in Washington for direct-to-consumer (DTC) genetic testing companies. Following public FDA meetings and a new round of FDA device notification letters earlier in the week, representatives from three major DTC genetic testing companies (23andMe, Navigenics and Pathway Genomics) were hauled in front of Congress today to defend their companies, their industry and the practice of DTC genetic testing.
The hearing on “Direct-To-Consumer Genetic Testing and the Consequences to Public Health” was conducted by the House Committee on Energy and Commerce Subcommittee on Oversight and Investigations. The meeting was chaired by Representative Bart Stupak of Michigan. Materials from the hearing, including a briefing memorandum, opening statements from Stupak and Representative Henry Waxman of California and witness testimony are available on the Committee’s website. Also available are materials from the Government Accountability Office (GAO) investigation into DTC genetic tests. These materials include the report the GAO submitted to Congress – “Direct-to-Consumer Genetic Tests: Misleading Test Results Are Further Complicated by Deceptive Marketing and Other Questionable Practices” (pdf) – as well as a YouTube video featuring excerpts from undercover phone calls made by the GAO to DTC companies as part of their investigation (both of which are discussed in detail below).
The Conversation Begins: Recap from Day One of FDA’s LDT Regulatory Meeting
Welcome to Hyattsville, MD, where we have just completed day one of FDA’s two day “Public Meeting on Oversight of Laboratory Developed Tests” (LDTs). The session was civil, well-organized and largely devoid of surprises. It did, however, mark the official kick-off of the FDA’s highly publicized decision to develop a “risk-based application of oversight” for all LDTs.
If you’re interested in the details of what was said and by whom you’ll find links at the bottom to all of the relevant transcripts, video feeds and Twitter coverage. For my part, here are the three key take-away points from day one:
Timing. Last week I wrote that it was unlikely that this meeting, or any of the other myriad regulatory and legislative proposals for LDT regulation, would produce a significant shift in the legal and regulatory landscape any time soon. One day of FDA meetings has done nothing to change that opinion.
Personal Genomics Goes to Washington
Next week, the eyes of the personal genomics world will be focused on Washington, D.C., where the FDA and Congress will be meeting separately to consider the industry’s future. First, the FDA will convene a highly-anticipated public meeting (July 19th and 20th) to “discuss how the agency will oversee laboratory-developed tests (LDTs).” The FDA announced last month a proposal to develop a “risk-based” approach to oversight of all LDTs – a broad category that includes the vast majority of genetic tests, including high-complexity diagnostic tests (IVDMIAs) and direct-to-consumer (DTC) genetic tests. Hot on the heels of the FDA meeting, on July 22nd, the House of Representatives Committee on Energy and Commerce – which two months ago launched its own investigation into the personal genomics industry – will hold a subcommittee hearing on “Direct-to-Consumer Genetic Testing and the Consequences to the Public Health.”1
While the genomics and personalized medicine communities anxiously await the upcoming FDA and Congressional meetings, yesterday the future of personal genomics was being debated on the opposite coast, at a policy forum in San Francisco entitled “Genomics and the Consumer: The Present and Future of Personalized Medicine” (pdf). The forum, which was hosted by California State Senator Alex Padilla (sponsor of S.B. 482, the so-called “bioinformatics bill”) and personal genomics company 23andMe, was filled with speculation from personal genomics investors, providers, customers and commentators about what the FDA and Congress might have in store for the field.
What Five FDA Letters Mean for the Future of DTC Genetic Testing
The FDA has published online letters sent to five personal genomics companies – 23andMe, Navigenics, deCODE Genetics, Knome and Illumina – informing the companies that they are manufacturing and selling medical devices without appropriate FDA premarket review and approval. No surprise that the news that the FDA has sent out letters to some of the most well-known providers of DTC genetic testing products is already making waves. (Daniel MacArthur was the first to point me to the AP story, and Mary Carmichael of Newsweek and Andrew Pollack of The New York Times were among the first to dive into the substance of the letters.)
Below, we will discuss the immediate and long-term implications of the FDA’s most recent regulatory actions for the five companies receiving letters, as well as for the DTC genetic testing industry. First, however, a review of the letters themselves is required. Each of the five two-page letters is signed by Alberto Gutierrez, Director of the FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), and follows a similar format throughout. To gauge the impact of these letters we will take them paragraph by paragraph.
Mapping the Personal Genomics Landscape
Last week saw the first annual Genomes, Environments, Traits (GET) Conference, in Cambridge, Massachusetts. Timed to coincide with DNA Day 2010, the conference marked one decade since the publication of the draft consensus human genome sequence. The GET Conference was billed as “the last chance in history to collect everyone with a personal genome sequence on the same stage to share their experiences and discuss the important ways in which personal genomes will affect all of our lives in the coming years.” Not quite everyone with a public personal genome sequence attended – Craig Venter, Desmond Tutu, Glenn Close were all unavailable – but a majority of the genomic pioneers were in attendance and the GET Conference was a one-of-a-kind event.
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.
More Myriad: Moving Beyond Single Gene Patents
Unless you have been living under a rock – or, if you hail from the Northeast, living under water – Monday’s decision in Association for Molecular Pathology v. USPTO is no longer new news. Previous coverage from the Genomics Law Report (here and here) reviews Judge Sweet’s opinion and its implications.
Moving Beyond Single Gene Patents. Much of the discussion following the decision has centered on what effect the invalidation of Myriad’s gene patents – should that decision be affirmed by a higher court and extended to other similar patents – will have on scientific and commercial innovation.
In many ways, that issue is at the center of the policy debate surrounding Sweet’s opinion and, more generally, the appropriateness of certain biotechnology patents. It’s a question that’s difficult to answer prospectively, but Andrew Pollack’s piece in The New York Times succinctly makes an important point about an emerging reality in the biotechnology industry.
…[T]he [biotechnology] industry is already moving to a period of somewhat less dependence on DNA patents for its sustenance. Diagnostic laboratories, for instance, are shifting from testing individual genes to testing multiple genes or even a person’s entire genome. When hundreds or thousands of genes are being tested at once, patents on each individual gene can become a hindrance to innovation rather than a spur.
Pigs Fly: Federal Court Invalidates Myriad’s Patent Claims
Late on the afternoon of Monday, March 29, 2010, Judge Robert W. Sweet of the United States District Court for the Southern District of New York issued a jaw-dropping summary judgment ruling (pdf) in Association for Molecular Pathology v. USPTO that invalidates certain of Myriad Genetics’ patents related to the BRCA 1 and 2 breast and ovarian cancer susceptibility genes. In a post written immediately after the release of the opinion, Dan gave a thorough summary of the ruling. Our objective here is to offer a bit more depth on what the ruling means—and what it doesn’t mean. On the one hand, Judge Sweet’s order is radical and astonishing in its sweep. On the other, it will be some time before we have any idea what impact it will ultimately have.
We should first disclose that one of us (John) has a dog in this fight, albeit a small one. In 2003, (along with biologist and patent lawyer Roberte Makowski), John published an article in the Journal of the Patent and Trademark Office Society entitled Back to the Future: Rethinking the Product of Nature Doctrine as a Barrier to Biotechnology Patents (pdf). In that article, Roberte and John laid out an argument for challenging Myriad-style patents on “isolated” genes as claiming products that are only trivially different from the naturally-occurring versions. Judge Sweet cited this article and, in several parts of his opinion, followed the roadmap it created. So, if you oppose the Myriad patents, you’re welcome; if you like them, we’re sorry.
What Summary Judgment Means. As Dan noted, and John first wrote last fall, it is rare for plaintiffs to win on summary judgment. For either side to receive summary judgment, it must show that there are no disputed issues of fact that require a trial to resolve, and that, on the undisputed facts, the law mandates judgment in its favor. This standard is especially hard for a plaintiff to meet, since it bears the burden of proof at trial. At the summary judgment stage, a defendant can usually create an issue of fact and thereby avoid summary judgment just by saying “they have the burden of proof at trial, and a jury might not believe them.” Although this is an unusual case in that the basic facts—most notably Myriad’s patent claims and the fundamental biology and genetics that makes possible those claims—really are not in dispute, a summary judgment ruling for the plaintiffs nonetheless sends a clear message about how strong this particular judge thought their case was—and how weak he thought Myriad’s was.
The Road to Invalidation. The court broke Myriad’s patent claims into two major groups: (i) those claiming isolated DNA sequences and (ii) those claiming methods for comparing or analyzing gene sequences to identify the presence of mutations corresponding to a predisposition to breast or ovarian cancer (p. 2). Both sets of patents were rejected under Section 101 of the Patent Act, which enumerates the permissible categories of patentable subject matter: processes, machines, manufactures, and compositions of matter. As the judge noted, a long history of cases forbids claims on laws of nature, abstract ideas, and natural phenomena, which include products of nature.
Breaking: District Court Rules Myriad Breast Cancer Patents Invalid
The highly anticipated decision in Association for Molecular Pathology v. U.S. Patent and Trademark Office, the frontal attack on Myriad Genetics’ breast cancer gene patents, was handed down today. A copy of the opinion, from Judge Robert Sweet of the Southern District of New York is available here.
The opinion was released late this afternoon and it weighs in at 156 pages, so a more complete analysis will be forthcoming. [Edit 3/30: John Conley and I have published a more detailed review and analysis of the decision here: Pigs Fly: Federal Court Invalidates Myriad's Patent Claims. For just the highlights, continue reading below.] However, there are a few crucial points that deserve an initial reaction.
1. The Plaintiffs Win. The ruling appears to be a nearly complete victory for the plaintiffs and their supporters, including the ACLU. With respect to Myriad’s issued patents on the BRCA1 and BRCA2 genes, Judge Sweet’s ruling invalidates both Myriad’s composition of matter claims (its patents on isolated DNA sequences to all or a portion of the breast cancer genes) and its method claims (those patent claims that relate to analyzing or comparing isolated DNA sequences in order to detect mutations in a patient’s BRCA1/2 genes that might cause breast cancer).
The overall tone of the Court’s ruling is best captured by this passage (from page 135):
The identification of the BRCA1 and BRCA2 gene sequences is unquestionably a valuable scientific achievement for which Myriad deserves recognition, but that is not the same as concluding that it is something for which they are entitled to a patent.
Why the State of Personal Genomics is Not as Dire as You Think
Another Tale of the Struggle of Personal Genomics, Full of Sound and Fury, Signifying…What? After a while, the personal genomics news cycle can begin to feel predictable. Recently, and not for the first time, there have been rumblings that personal genomics pioneer 23andMe is struggling. The most recent “news” appears to be a December SEC filing disclosing a $4 million payment to an unidentified 23andMe executive. Gene Expression and BNET have taken the opportunity to recycle some of the company’s previous financial struggles, including co-founder Linda Avey’s departure and a well-publicized round of fall layoffs, and to speculate broadly about the state of morale at the company in addition to the well-being of the personal genomics industry more generally.
Avey herself, perhaps unintentionally, has fueled speculation that something may be afoot with a pair of recent posts (the original post has now been combined with an update) on her own blog. Avey has launched a preemptive strike against what appears to be an upcoming New York Times piece that will “question[] the viability” of the personal genomics industry and “hits too close to home” for Avey not to comment. (Or, as GenomeWeb headlines it, Linda Avey Versus the New York Times.)
Perhaps all of the smoke signifies a smoldering fire at 23andMe. Then again, it may represent nothing more than periodic reverberations from the social media echo chamber, where common memes are repackaged and recycled at regular intervals.
