FDA vs. 23andMe: How do we want genetic testing to be regulated?

Yesterday the US Food and Drug Administration sent a letter to the human genetic testing company 23andMe giving them 15 days to respond to a series of concerns about their products and the way they are marketed or risk regulatory intervention. This action has set off a lot of commentary/debate about the current and future value of personal genomics, whether these tests should be available direct to consumers or require the participation of a doctor, and what role the government should play in regulating them.

I am a member of the Scientific Advisory Board for 23andme, but I am writing here in my individual capacity as a geneticist who wants to see human genetic data used widely but wisely (although I obviously have an interest in the success of 23andme as a company – so I can not claim to be unbiased).

I see a wide range of opinions from my friends on this matter – ranging from “F**k the FDA – who are they to tell me what I can and can not learn about my DNA” to “Personalized genomics is snake oil and it’s great that the FDA is stepping in to regulate it”. I fall somewhere in the middle – I think there is great promise in personalized genetics, but at the moment it is largely unrealized. Looking at your own DNA is really interesting, but it only rarely provides actionable new information. I don’t think the FDA should restrict consumer access to their genotype or DNA sequence, but I do think the government has an important role to play in ensuring that consumers get accurate information and that the data are not oversold in the name of selling products.

As people try to decide what kinds of tests and information should be available and how the government should regulate them, I think it’s useful to ask a series of questions.

1) Should a person be able to have their DNA sequenced and get the data?

Putting aside any questions about how useful this information is right now and how it is marketed, do you think companies should be able to offer a service where consumers send in a spit or blood sample and a few hundred dollars and get their genome sequenced in return? (23andme currently provides SNP genotyping, not whole genome sequencing, but we’re very close to the point where human genome sequencing is cheap and reliable enough to make this possible.)

I think the answer is obviously yes. I can’t see any good argument for why we should prevent people who to from obtaining their own DNA sequence.

Which leads to:

2) Should a person who has had their genome sequenced be able to access scientific literature relevant to their genome? 

Again, putting aside questions about the accuracy or utility of this information, there is a lot of published scientific literature that is potentially relevant to people with a particular genotype (including genome-wide association studies as well as a lot of classical human genetic literature and other functional studies). Assuming someone has their own genome sequence, it would be hard to argue they shouldn’t have access to information that would allow them to understand what their genome means.

Which leads to:

3) Is there a role for third parties in helping people interpret their genome sequence? 

The problem with the previous question is that it would be next to impossible for someone to actually interpret their genome simply by perusing the scientific literature (and I’m not even going to get started on the fact that much of this literature is behind paywalls). Even trained human geneticists wouldn’t do that. They’d go to some website – OMIM, DECIPHER, etc… – and use various automated tools to extract what is known about their genotype.

But few people have the technical savvy to be able to analyze their own genome in this way. So, assuming there is interest, there is a great niche for third parties to step in an provide services to people to help them interpret their own DNA. Is this a bad thing? Again, I don’t see how it is – assuming that these third parties provide accurate information (more on this below).

Should this third party be a doctor, as some (mostly doctors) are arguing? There are certainly doctors out there who have a great grasp of human genetics. But there aren’t a lot of them. And even the doctors who do know the world of human genetics inside and out aren’t in a position to help people navigate every nook and cranny of their genome. This is a job for software, not for people.

If you accept points 1,2 and 3 above – which to me seem inarguable – then you accept the right for companies like 23andme to exist. You might not think they provide a valuable service. You might not think they do a good job at providing these services. But you can’t argue – as many are now doing – that direct-to-consumer genetic testing companies should be shut down.

Should direct-to-consumer genetic testing companies be regulated? 

I think this is also a no-brainer. Obviously they should be regulated – and fairly tightly so in my opinion. Few consumers have the capacity to judge on their own whether the genetic testing services provided by a company are accurate and whether interpretive information provided by third parties is valid. It is vital that the FDA protect consumers in two ways: 1) by validating the tests and the companies that provide them, and 2) by monitoring genetic information that is provided by consumers – especially if it is being used to market tests or other products. The former seems relatively easy – validating genotyping and sequencing is well-trodden turf. The latter is a bit more complicated.

If genetics were simple and our understanding of it were complete, companies could provide accurate reports that say “based on your genotype, your age and personal history, you have a 7.42% chance of developing ovarian cancer in the next 10 years”. However, we are far, far, far away from this. We have an incomplete catalog of human genetic variation; known genetic variation can explain only a small fraction of the heritable component of most phenotypes of interest; we have a poor understanding of how different genetic variants interact to affect disease risk or other phenotypes; and we have essentially no capacity to incorporate environmental effects into predictive models. In many cases current, incomplete, data may point to someone having an elevated risk of some disease, when they really have a lower than average risk. And, to top it all off, there are very few cases where knowing your risk status or other phenotype points to genotype-specific actions (with the BRCA status referred to in the FDA letter a notable exception).

The data are, at this point in time, very very messy. I don’t think anyone disagrees with that. The question is what to do about that. One the one side you have people who argue that the data are so messy, of so little practical value, and so prone to misinterpretation by a population poorly trained in modern genetics that we should not allow the information to be disseminated. I am not in this camp. But I do think we have to figure out a way for companies that provide this kind of information to be effectively regulated. The challenge is to come up with a regulatory framework that recognizes the fact that this information is – at least for now – intrinsically fuzzy.

The FDA wants to classify genetic tests like those offered by 23andme as medical devices, and to apply the appropriately strict criteria used for medical devices to genetic tests. But the problem with this is that contemporary genetic tests will almost certainly fail to meet these criteria, and I don’t see who benefits from that scenario. Genetic tests are simply not – at least not yet – medical devices in any meaningful sense of the word. They are far closer to family history than to an accurate diagnostic. The FDA and companies like 23andme need to come up with standards for accurately and honestly describing the current state of knowledge for genotype-phenotype linkages and their application to individual genotypes. They need to establish what generic statements can and can not be used to market genetic tests so that people don’t purchase them with unrealistic expectations about the kinds of information they will provide. Let’s hope this flareup between the FDA and 23andme is the spark that finally makes this happen.


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