When the FDA shut down biotech company 23andMes direct-to-consumer Personal Genome Service, many in the biotech community worried that the FDA was risking the survival of a nascent industry that would revolutionize medical care with new genetic technologies. But lost in the story about 23andMe was the news that the FDA had just issued its very first approval for a next-generation DNA analysis machine, clearly signaling that the agency recognizes the growing significance of genetic testing in medicine.

The FDA approved a machine called the MiSeqDx, the first FDA-regulated test system that allows laboratories to develop and validate sequencing of any part of a patients genome. For a few hundred dollars, this little machine can analyze an amount of DNA in 24 hours that, 10 years ago, would have taken a dozen machines two weeks and cost nearly a million dollars. The rate of improvement in our technical capacity to read out DNA has been stunningly rapid, outpacing even the expectations of Moores Law, the gold standard for progress in the computer industry. Biomedical researchers can now consider ways to bring DNA analysis into the clinic that would have been impossible before. Rather than testing for mutations in one gene at a time, and in only very specific groups of patients, its becoming feasible to scan much larger portions of a patients DNA as part of a routine health assessment for everyone. Whats happening in medical genetics is the equivalent of having the operating costs of a private jet suddenly drop to those of a Honda Civicin which case youd probably start considering previously unthinkable destinations for not only the annual family vacation, but for three-day weekends as well.

In a report issued last fall (PDF), the FDA laid out its view of the regulatory challenges posed by personalized genetic medicine. At issue is the idea that with cheap, accessible DNA analysis, medical care can be personalized to match each persons genetic makeup. Cancer diagnoses, rather than being based on abnormalities that are visible under a microscope, would instead be classified more effectively by their underlying genetic mutations. The typical trial-and-error approach to find the right drug for a patient suffering from depression would give way to a genetic test that would indicate the best drug.

It sounds great in principle, but the result is a major headache for the FDA, because modern genetic medicine is demolishing regulatory concepts and categories that the agency has long used to ensure that drugs and diagnostics are safe and effective.

Take genetic tests for instance. The two primary criteria the FDA uses to evaluate diagnostics are analytical validity and clinical validity. As the FDA report describes them, analytical validity refers to how well the test measures what it is supposed to measure, whereas clinical validity looks at how well the test predicts who has or does not have a disease or condition for which it is being tested. A typical diagnostic test is required to be both analytically and clinically valid, but for large-scale genetic tests this doesnt make sense. Tests that analyze hundreds or thousands of regions of your DNA at once can be analytically validthat is, they accurately determine the identity of mutations in your genomebut the clinical validity will vary with the individual mutation, depending on whether that mutation has a discernible effect. Furthermore, clinical validity for any one mutation will often be in flux, as new research clarifies the role of poorly understood mutations.

Another challenge with personalization is that a drug and a diagnostic test are more likely to be paired in their development. Some drugs, like the cystic fibrosis drug Kalydeco, are deliberately targeted only at patients with a specific mutation. Pairing genetic tests with therapeutics makes it difficult to track down the source of problems when something doesnt work. As the FDA report notes, An adverse event associated with the use of a therapeutic product may have arisen as a result of failure of the test to identify the optimal subset of patients due to design deficiencies, manufacturing deficiencies, or operator error.

To respond to these challenges, the FDA report describes the changes youd expect from a large and complex government agency tasked with keeping up with a large and complex industry. There are restructurings, efforts to increase communication and coordination among different agency centers, and committees to rethink the process by which some new treatments and diagnostics are approved.

WHILE THE FDA MAY be making an admirable effort to confront the issues raised in the report, the authors ignored the elephant in the room: the wild frontier of direct-to-consumer genetic testing, represented by 23andMe. Consumer-oriented genome services undermine one of the biggest regulatory concepts that the FDA depends on: whether or not something counts as a medical diagnostic device. Does the FDA need to protect you from information about your genome, especially if some of that information is potentially unreliable? Or should anyone be able to buy a tentative analysis of their genome based on the latest research?

This is where medical genetics shades into recreational genetics. It doesnt help that these services are often advertised with the dubious claim that they will empower you to take your health into your own hands. As a group of researchers, physicians, and health policy experts noted in a recent commentary, there is little evidence to support the basic premise implied by the empowerment rhetoricnamely that individuals will use genomic risk information to adopt a healthier lifestyle and, thus, reduce their risk for chronic diseases.

Even if a personal genome analysis is not useful yet, it is hard to make the case that we should be barred from it. These services feed our curiosity about ourselves, and they are an opportunity to educate consumers about genetics. Of course our genetics are inextricably tied up with our health, which means that direct-to-consumer genetic services will always threaten to impinge on the FDAs territory. How it should respond is an issue not yet resolved.

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CGS : The FDA Is Not Anti-Genetics

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