DNA DTC: The Return of Direct to Consumer Whole Genome Sequencing

This morning, Gene By Gene, Ltd. – better known as the parent company of the popular genetic genealogy provider Family Tree DNA – formally announced a corporate reorganization that includes the debut of a new division, DNA DTC. (Apparently the news was also announced earlier this month at the Family Tree DNA Conference, although the company waited until today to launch press releases.)

The announcement from Gene By Gene is newsworthy for several reasons, including:

1. The Return of True DTC Whole Genome and Whole Exome Sequencing. According to DNA DTC, the company offers a range of products “utilizing next generation sequencing including the entire exome (at 80x coverage) and the whole genome.” The company’s website, while fairly spartan, appears to bear this out. Whole exomes ($695 at 80x coverage) and genomes ($5,495 at 30x coverage) are both listed as available products.

Now, Gene By Gene is not, as its Wikipedia page claims (as of this writing), “the first commercial company to offer whole genome sequencing tests.” Knome earned that honor more than four years ago, when it started selling whole genome sequences for $350,000; an astounding price, either low (given the cost of the first human genome was $3 billion) or high (given that, well, it was $350,000) depending on your perspective. Gene By Gene probably does represent, however, the only commercial company currently offering a whole genome sequence in a truly direct-to-consumer (DTC) manner.

Knome, the DTC whole genome sequencing pioneer, has left the DTC business, focusing instead on genomic interpretation for commercial and academic customers. Knome briefly had some competition for DTC whole genome sequencing from Illumina, but Illumina’s offering – while still around – requires the extensive involvement of a medical professional in both the ordering and return of the individual’s genomic results.

The Genomics Law Report has discussed, several times (see here and here), what the label “direct-to-consumer” really means in the context of genetic testing, given the myriad companies and products to which that label is applied. However, in its most commonly used and complete formulation, a DTC genetic product (e.g., a genetic test or service) is one that an individual can order, receive, review and share with others without being required, at any stage in that process, to engage a healthcare professional (e.g., a physician or a genetic counselor) as an intermediary. While not everyone believes that sort of DTC model is a good idea, that model remains the one that most people – proponents and critics alike – appear to have in mind when they talk about “DTC.”

As far as can be ascertained from DNA DTC’s website, as well as its press release, the company qualifies as a provider of true DTC genetic/genomic products. 23andMe, the acknowledged market leader in DTC genetic testing, employs the same DTC model, but it’s exome pilot product ($999) continues to remain closed to new customers and the company does not (yet) offer a whole genome sequencing service. Thus, DNA DTC appears to be the only company currently offering a truly DTC whole exome or whole genome product.

2. The First Data-Only DTC Product. Taking a closer look at DNA DTC’s product offerings reveals something else interesting: the company appears to be selling data-only products. For DNA DTC’s exome product, the company notes simply that “we disclose the variants that have been identified, however no analysis or interpretation will be provided.” The company’s whole genome sequencing product description is even more direct: “data analysis not included.”

From the outset of DTC genetic testing, the goal for almost every company has been customer engagement, with the genetic test itself invariably paired with some type of interpretive service aimed at assisting the customer in understanding and exploring their personal genomic data. Some of these services – including Family Tree DNA’s own “Family Finder” service – have certainly been more successful than others, but never has any meaningful participant in the DTC marketplace offered a product without any interpretation or analysis whatsoever (i.e., raw data only). That appears to have changed with DNA DTC.

There are several possible explanations for this. First, as has been much discussed over the past two years, analyzing and interpreting a whole genome sequence is not free. Nor is it easy. Just how expensive and difficult it is has been the subject of much debate (see this Genomes Unzipped piece by Daniel MacArthur for a helpful discussion), but if you’re going to offer whole genome sequencing for under $5,500, your profit margin will undoubtedly be higher if all you are providing is the raw sequence data.

Second, while the FDA has indicated at intervals in the past few years that it intends to more closely scrutinize the DTC genetic testing industry, the FDA has never suggested – nor do I think it likely – that the agency intends to turn its regulatory gaze upon providers of raw genetic or genomic data. Much more likely is that, if and when the FDA acts again in the DTC marketplace, the agency will focus on specific interpretive claims made by DTC products, perhaps requiring companies to take those claims with potential clinical relevance through the FDA premarket approval/clearance process. 23andMe started this process over the summer and, perhaps, DNA DTC is seeking to skirt the time, expense and uncertainty associated with an FDA review by simply eliminating all interpretation and analysis (and thus all potentially problematic claims) in connection with its DTC products.

The lack of any reasonable possibility that DNA DTC could be alleged to be providing a clinical genetic test may also help explain why DNA DTC’s press release features a Senior Vice President at Illumina (Matt Posard) pronouncing Illumina to be “…very excited to be involved in building such a well rounded offering.” At first blush, this might seem like a risky move for Illumina given that (a) it has already received one letter from the FDA warning the company against knowingly providing research use only (RUO) devices to DTC genetic testing companies and (b) last summer the FDA published stringent new draft RUO/IUO guidance warning providers of RUO/IUO devices (like Illumina) not to sell such products to laboratories they know use products other than for research or investigational purposes. Presumably, however, the lack of any interpretation or analytic service in connection with the DNA DTC products (along with Illumina’s ongoing – and since 2010, at least, publicly unchallenged by the FDA – relationship with 23andMe, which uses a very similar Illumina RUO product to the one used by DNA DTC in its genotyping product) convinced Illumina that there was no material risk of FDA action over this particular DTC supply relationship.

3. An Impetus for Interpretation-Only Products? The real question of course, is whether consumers will line up to purchase any of these bare bones genomic data products from DNA DTC. While neither the exome nor the whole genome products are cheap in the abstract, they each still likely represent the cheapest option in their respective classes for individuals looking to directly access their genomic information. (Note, however, that the $5,495 price tag on the whole genome product may be misleading as, at least as of this writing, it was only possible to place in order in multiples of three genomes, raising the actual price tag to $16,485.)

For the motivated consumer (with several hundred or thousand dollars of disposable income), there is plenty that might be done with even raw genomic information, including taking advantage of free genomic interpretation services such as Promethease or openSNP. However, both of those services are aimed at relatively sophisticated users of genomic information and, morever, since it’s currently unknown exactly how DNA DTC returns data to its customers, it’s possible that such services may not integrate well or at all with DNA DTC.

More importantly, even if current services are interoperable with DNA DTC, how many potential consumers fall into this category? Certainly dozens. Possibly hundreds. Anything much beyond that, at least today, seems very unlikely.

What is easier to imagine, although likely not imminent, is the future emergence of a more consumer-friendly genomic interpretation service that would integrate, directly or indirectly, with low(er)-cost, data-only providers like DNA DTC to guide consumers from data receipt to interpretation. In many respects this is exactly what Knome has already done in a different corner of the genomics marketplace, pivoting from a provider of genomic sequence data to a platform-agnostic provider of genomic interpretation services. There’s no obvious reason why something similar couldn’t one day happen in the DTC marketplace, assuming sufficient consumer demand. It’s not too difficult to envision an interpretation-only company offering to improve the experience of understanding and managing otherwise unwieldy consumer genomic information just like, for example, Mint.com already does for otherwise unwieldy consumer financial information.

4. Building a Genomic Data Resource (Without Telling Anyone)? While it seems unlikely that consumers will be beating down DNA DTC’s door any time soon, a word of caution to any would be consumers: remember to carefully read the company’s Terms and Conditions and Privacy Policy. Beyond the usual egregiously one-sided limitations of liability, warranty disclaimers and indemnification provisions that so frequently afflict website terms and conditions, DNA DTC’s policies clearly suggest that the company intends to partner with third parties to conduct “scientific/medical research or conduct or support the development of drugs or devices.” That in and of itself is not so unusual, as plenty of other DTC companies, including 23andMe, have indicated an interest in leveraging their customer data for commercial gain.

What is concerning is that, apparently, DNA DTC is entitled to share it’s customers’ genomic information without specific and informed consent. Here is the operative language from the Privacy Policy:

If you have given consent to participate in any of the Gene by Gene services offered by any of the websites owned and operated by Gene by Gene as described in a specific consent document, we may have your record, information or test results disclosed to third parties for the purpose of publication in a peer-reviewed scientific journal. From time to time, we may ask for explicit consent to participate in a specific research, and upon this consent we may allow research contractors to access your test results, which will be kept anonymous, for the purpose of conducting scientific research. In addition to providing its customers with answers to their genetic related questions, Gene by Gene also aims at advancing genetic knowledge and creating, commercializing, or undertaking activities toward the practical applications that may lead to the improvement of health care. If you do not give your explicit consent to participate a specific research, Gene by Gene may still use your record, information or test results for purposes such as quality control or other R&D activities. Records, information or test results used for such purposes may be disclosed to third-party research partners who will not publish the information in a peer-reviewed scientific journal. Research partners may include commercial or non-profit organizations that conduct or support population genetic studies, scientific/medical research or conduct or support the development of drugs or devices to diagnose, predict, or treat health conditions. (emphasis added)

In short, while it appears that Gene By Gene (the legal entity responsible for DNA DTC) might ask for customer consent for certain research projects, where consent is either not requested, or not granted, the only restriction on Gene By Gene’s use of customer genomic information is to refrain from publishing that information in a peer-reviewed scientific journal. Needless to say, that’s not much of a restriction.

Given the newness of the DNA DTC venture, it’s possible that this represents unintentional ambiguity and not an attempt to entice customers to purchase low-cost genomes and exomes while building, behind the scenes and buried in DNA DTC’s Privacy Policy that only a few people will likely ever read, a database of genomic information that Gene By Gene can use – perhaps in parallel with its already massive database of genetic genealogy records – in pursuit of profitable (at least to the company) research and other commercial collaborations. Then again, it would not be the first attempt by a DTC genetic testing company to do just that (although TruGenetics quickly disappeared from the DTC scene).

Either way, prospective customers who care how their genomic information is used (and, of course, not all do) would be well-advised to clarify directly with the company just how it intends to use their information, as well as when explicit consent will be required. They should also ensure that the company’s answers are consistent with its written policies. And DNA DTC, for its part, would be well advised to preemptively clarify the same with its prospective customers, as the backlash over 23andMe’s patent issuance earlier this year helps to illustrate.

5. Something New for DTC. Apart from 23andMe, recent developments in the field of DTC genetics have largely involved companies either turning away from a true DTC approach (e.g., Pathway Genomics, Counsyl), leaving the field altogether (e.g., Navigenics) or simply pricing themselves out of the marketplace, thereby eliminating any likely controversy (e.g., deCODEme).

There’s good reason to be skeptical about the commercial potential of DNA DTC’s product offerings, particularly given the lack of any interpretation component and uncertainty surrounding how the company intends to use its customers’ data. Nonetheless, it’s impossible to deny the success Gene By Gene has had with its Family Tree DNA business and, whether DNA DTC succeeds or not, it’s refreshing that the (non-ancestry) DTC genetics/genomics field appears to have a new entrant offering a (somewhat) new product and an (apparently) new business model.

It may feel as if DTC genetic testing has been around forever, but in reality the industry just turned 5 years old this month. And as in any nascent industry, an attempt at a little innovation – as well as a little disruption – is almost always a welcome development.

Filed under: Direct-to-Consumer Services, FDA LDT Regulation, General Interest, Genetic Testing/Screening, Genomic Sequencing, Genomics & Society, Industry News, Informed Consent, Privacy
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