In my last post about my UNT applied anthropology thesis, for which I conducted an ethnography of direct-to-consumer genomics (DTCG), I discussed genealogical DNA tests. This post we will be discussing DNA and health testing.

The Start of DNA Health Testing

Riding the wave of decreasing costs and building on the success of DTCG consumer genealogical testing, companies started to emerge to offer health testing outside of the clinical setting.  The first wave of health tests that emerged primarily fell into the predictive category of DTCG health tests. At this time, there were three companies offering tests in that space (Williams-Jones 2003). Following this, in 2002 susceptibility tests started to hit the market providing information on gene variations that may predispose an individual to develop common health conditions or have certain traits. Common examples included genetic variation in drug response, clotting disorders, fetal sex, hereditary hemochromatosis and nutrition (McBride, Wade and Kaphingst 2010). Sciona, an example of a DTCG company focused on nutrigenetic testing, analyzed consumers’ DNA to look for genes related to nutrient metabolism and provided personalized dietary recommendations (Hogarth and Saukko 2017).

DNA Health Testing Goes Mainstream

Building on the success of these earlier companies 2003 to 2007 saw an explosion in the market with a fourfold increase (14 to 53 tests) in the number of available DTC genetic tests (Goddard, et al. 2009). Within this new group of companies were Navigenics and 23andMe. Both were very well capitalized compared to their competitors. Both were also respectively well aligned to the leading DNA sequencing chip companies, Affymetrix and Illumina, who produced chips that were used to rapidly sequence portions of genomes. These chips were helping to fuel genome-wide association studies in which hundreds of thousands of genetic variants are examined in large numbers to detect gene-disease associations, which in turn was fueling the ever-increasing number of susceptibility tests that could be offered to consumers. Given this opportunity, Affymetrix and Illumina were also looking to move into this new DTCG space of commercial test to increase their market share.

Likewise, the market collectively diversified away from only the traditional biomedical space, and by the fall of 2007, there were 27 distinct online DTC testing websites offering 53 unique health tests in the price range of $90 to $5400 (McBride, Wade and Kaphingst 2010). Building on the advancements and collaborations within the genetic industry, Navigenics and 23andMe also formed collaborative partnerships with Microsoft and Google respectively (Hogarth and Saukko 2017). Together, this alignment between sequencing chip manufacturers, well-capitalized DTCG startups, and tech giants capable of storing vast amounts of data helped to set the stage for a new era of DTCG.

Riding on the back of the confluence of forces that came together over the past few years to make health testing almost as approachable as genealogical testing, the second wave of companies such as 23andMe, Navigenics, and deCODEme began offering complex tests in late 2007 that cost in the range of $429–$1000. These tests, compared to some of the earlier tests which analyzed only a few hundred gene variants, were now analyzing thousands (McBride, Wade and Kaphingst 2010). Given this new opportunity, the testing companies began to expand their product offerings deeper into the wellness and medical market and started to advertise on social media actively.  This series of events, along with media coverage like Time Magazine naming the Retail DNA Test the 2008 Invention of the Year led to an increase in awareness of DTCG health testing (Time Magazine 2008). However, with the growing awareness came increased scrutiny.

DNA Health Testing Under Scrutiny

The scrutiny started in 2006 when the U.S. Federal Trade Commission (FTC), Food and Drug Administration (FDA), and Centers for Disease Control and Prevention (CDC) published an FTC Fact for Consumers report titled At-Home Genetic Tests: A Healthy Dose of Skepticism May Be the Best Prescription. The fact sheet stated consumers should “be wary of claims about the benefits these products supposedly offer,” and “while these tests may provide some information your doctor needs or uses to make treatment decisions for a specific condition, they are not a substitute for a physician’s judgment and clinical experience” (Federal Trade Commission Bureau of Consumer Protection Division of Consumer and Business Education 2006, para. 10, para. 13). This was followed by the U.S. Government Accountability Office (U.S. GAO) study of four nutrigenetic testing companies. The study found that the test results predicted the consumers were at risk of various diseases, even though the tests themselves carried disclaimers stating they were not intended for diagnosis (United States Government Accountability Office 2006).

By 2008, when the second wave of DTCG testing kits from 23andMe, deCODE and Navigenics were starting to gain market share, the FDA was debating whether or not they should start regulating a certain type of Laboratory Developed Test (LDT) known as In Vitro Diagnostic Evaluation and Safety (IVDMIA). The reason for debating the issue focused on concerns regarding analytic validity, the reliability of the actual genetic test and laboratory performance; clinical validity, whether the genetic variant corresponds to the condition or trait, and consumer comprehension (Curnutte 2017). The corollary to this FDA debate was whether or not the potential regulation of LTDs should be extended to genetic tests. In the end, no decision was made, and DTCG companies continued operating relatively unencumbered.

As prices declined further, advertising and media coverage continued to increase, resulting in growing market share. These developments led other critical players outside of the regulatory agencies to get involved in the debate. Leading scientists such as the National Institute of Health (NIH) soon-to-be chief Francis Collins, and Craig Venter, one of the driving forces of the Human Genome Project (HGP) to speak up. They were calling for more transparency, which led Congress to request that the U.S. GAO launch a second study (Genomic Law Report 2010). This study sought to detail the reliability of the tests and company privacy policies. The findings were discussed in a 2010 Congressional hearing that involved experts testifying that the DTCG company information was not sufficient for medical use and was instead only “for entertainment purposes”  (Spector-Bagdady 2015, 569).

FDA Regulation of Genetic Testing

Congress echoed the report findings and stated that the DTCG companies misled consumers and used deceptive marketing practices. The FDA then sent warning letters to 15 DTC firms to notify them that their tests were, in fact, medical devices, and therefore, under the jurisdiction of the FDA (Curnutte 2017). In the letter to 23andMe, the FDA stated “The 23andMe Personal Genome Service™ is a device under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h) because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body” thereby finally making it legally clear where the FDA stood on the matter (Food and Drug Administration 2010, para. 1).

Following this, some of the companies, led mainly by 23andMe, started working more closely with the FDA. However, in the case of 23andMe, which was the clear market leader for DTCG health testing at the time, this trend seemed to stagnate after they failed to deliver on a January 2013 promise that they would share more data with the FDA. In May of that year, 23andMe stopped communicating according to the FDA, despite the fact that 23andMe had recently launched a $5 million advertising campaign. This breakdown in communication led to the FDA sending a cease and desist letter on November 22, 2013, ordering 23andMe to stop marketing its product (Hayden 2017).

In the letter, the FDA stated: “even after these many interactions with 23andMe, we still do not have any assurance that the firm has analytically or clinically validated the Personal Genome Service (PGS)” (Food and Drug Administration 2013, para. 6) The FDA statement was made based on 23andMe’s “health reports on 254 diseases and conditions, including categories such as carrier status, health risks, and drug response, and specifically as a first step in prevention that enables users to take steps toward mitigating serious diseases” (Food and Drug Administration 2013, para.2 ). After this, 23andMe was able to operate still and provide trait and ancestry tests, but the medical tests that the FDA had classified under medical devices could no longer be sold.

But determined to get back to selling their health tests, 23andMe, under the guidance of a legal team, began cooperating with regulators. Through the process, the regulatory environment that was to govern the DTCG industry going forward gradually came into focus for all parties, and controls were detailed by the FDA to make it more transparent what steps needed to be taken to provide adequate assurances of safety and efficacy. DTCG companies wishing to sell over-the-counter (OTC) tests would need to give consumers information about the biological sample collection device itself, which must get FDA clearance and the details about the test’s analytical performance. The FDA also wanted to see documentation on other instrumentation and software used in the testing process.

With these new guidelines in hand, 23andMe began the process of obtaining approval for a DTCG health test, and at the end of 2014, asked the FDA to approve one such test. The test was for Bloom Syndrome and was intended to inform consumers if their children might inherit a genetic risk for the disease. 23andMe seemingly started with the Bloom Syndrome test because it is a carrier screening test, which implies the test informs consumers if they are carrying one or more copies of a gene, but does not necessarily mean that the disease will be inherited. Therefore, the tests results do not provide a disease diagnosis. This point was critical, as demonstrating the validity of identifying a single gene disease is much easier than a polygenic disease. As part of the approval process, the FDA also required 23andMe to address utility concerns, requiring them to test users for comprehension, requiring a score of 90% or greater for each comprehension concept (Curnutte, 2017). 23andMe complied, and with all of the requirements met by early 2015, the FDA approved the test in February 2015, making it the first FDA approved DTCG test in the United States available for sale to consumers.

In their approval letter to 23andMe, the FDA stated “The FDA believes that in many circumstances it is not necessary for consumers to go through a licensed practitioner to have direct access to their personal genetic information. Today’s authorization and accompanying classification, along with FDA’s intent to exempt these devices from FDA premarket review, supports innovation and will ultimately benefit consumers. These tests have the potential to provide people with information about possible mutations in their genes that could be passed on to their children,” and a result, a near fifteen-year period of uncertainty had seemed to come to an end (Reuters 2015, para. 6).

Following this, 23andMe once again took the lead, and by April 2017, through cooperation with regulators, they were approved for another ten disease-related susceptibility tests, which they achieved by conducting “extensive validation studies for accuracy and user comprehension that met FDA standards” (23andME 2017, para. 5). As a result of this process, they have helped prepare the way for many other DTCG companies, and in the process helped to push the FDA to articulate the required controls. The question now is when, why and how will the majority of consumers adopt DTCG health tests?

Recommended Video

At TEDx Scranton 2020, I gave a talk titled Are DNA Tests Safe? If you are interested in the topic of consumer DNA tests, you will find it relevant.