The audacity of interpretation: Protecting patients or piling on?

In November 2013, the United States Food and Drug Administration set off a media firestorm (or what passes for one in our world) when it sent a warning letter to the highest-profile direct-to-consumer genetic testing company, Silicon Valley-based 23andMe (Gutierrez, 2013). The company, the agency alleged, had committed a litany of transgressions during its six years in business, most notably violation of the Federal Food, Drug and Cosmetic Act by marketing its spit kit and Personal Genome Service (PGS) as a medical device without proper FDA clearance. By doing so, the FDA averred, 23andMe had put its customers at risk because they might “self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome” of the company's PGS test. Or, in the case of hereditary breast and ovarian cancer caused by mutations in the BRCA1 and BRCA2 genes, “if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist” (Gutierrez, 2013). Setting aside all of the other complaints in the FDA's missive (e.g., the company launching a high-profile ad campaignwhile ignoring the agency's communiqués for months on end), the implications were clear: as far as the FDA was concerned, 23andMe could not be trusted to dispense information on genetic risks for actionable traits with fairly high penetrance like drug response and Mendelian forms of cancer. This aspect of l'affaire 23andMe was a surprise: recent criticism of the company's assessment of a single pharmacogenetic locus notwithstanding (Brownstein et al., 2014), it seems to me that most—and arguably themost robust—criticisms of the substance of DTC genetics companies' offerings have been directed at their speculative and often contradictory lifetime risk estimates for complex diseases derived from genome-wide association studies (Peikoff, 2013; Ng et al., 2009; Janssens et al., 2011; Kido et al., 2013; Kalf et al., 2014). Thus, for the FDA to attack the company's assessment of the genetic basis of warfarin metabolism or BRCA alleles seemed less convincing: would any self-respecting surgical oncologist subject a woman to a radical mastectomy and/or oophorectomy based on nothing more than a $99 direct-to-consumer test that examined three known pathogenic alleles out of many hundreds (Meric-Bernstamet al., 2013)? Thiswould be akin to anob-gyn forgoing both a blood hCG pregnancy test and a pelvic exam because her patient had already reported a positive home pregnancy test.