DTC in a Gene Sequenced World

July 20, 2010

I am watching the much anticipated FDA public meeting on Laboratory Developed Tests (July 19-20, 2010).  This meeting is the follow up, if you will, to the recent letters that FDA sent to Pathway Genomics (planning a drug store sold genome test kit) and a number of other companies.  It occurs to me that most of what this group is discussing this will be made moot in 5-10 years by whole genome sequencing (WGS) technology.

The primary argument against direct-to-consumer (DTC) genomic testing is that consumers will either (1) have anxiety about the interpretation of the results or (2) use the information to make (stupid) medical decisions without a physician.  The discussion today is all about how, or if, the FDA should regulate DTC Laboratory Developed Tests.  Most regulators and physicians seem to be strongly in favor of limiting access to genomic testing so that your doctor is the one ordering the test and helping you interpret the results.  Business is dancing around a bit because they cannot come out against the FDA.

One reasonable position is that the FDA cannot really regulate away anxiety or stupidity.  If you think it should, maybe FDA should take away my bathroom scales and only let me weigh myself with a physician around.  I might have some anxiety (gasp) if gain weight and then realize that being overweight increases the odds of heart disease, diabetes, etc.   Even worse, you know when you have a symptom and go to Google to find a matching disease?  High anxiety.  Now your blood pressure goes up so google that, too.  You might even take some medical action based on that information (vitamins, exercise, go see a doctor, order a home liposuction kit).  It seems to me that, if access to information causes you anxiety or would make you do something stupid, quit using the internet (or ask the FDA to regulate it) because there is more poor quality information out there than good information.  Anyway, I don’t really buy the argument that we cannot handle information about our health.  We make decisions about our own medical treatment every day…do I have that spot looked at, is that chest pain from working out or a heart attack, should I eat that hamburger.

Regardless of whether you agree that the FDA should be in the business of guarding against anxiety and misinterpretation of scientific information, I suspect that the FDA is not going to be able to regulate it in the same way in the future as it could today.   Here is why:

The Cost of Genome Sequencing is Dropping Precipitously

If it costs $1,000 to sequence a whole genome in 2-4 years (uncertain but this seems to be the consensus among experts I’ve talked to) then I am guessing we get to $200-500 in less than 10 years.  Somewhere in there we hit the point where many, many people will be willing to self-pay for their own genetic information.  Or business models arise where you get sequenced for free.  That’s one traditional barrier (cost) gone.  You don’t need a blood draw either.  All you have to do is put a swab in a tube and mail it along to a lab.  Cheap and easy.  That’s another barrier to self testing (health care industry gatekeeper) gone.

If people want to self pay, can the FDA justify regulation of simple sequencing?  If they do, will consumers just mail it to a lab that is offshore.

WGS Output is a Database that can be Re-analyzed Again and Again

The nature of WGS information is fundamentally different from the results of current technologies used for molecular diagnostics.  When you are tested for specific mutations via microarray or PCR, you get back the interpretation (Dear Mr. Smith or Mr. Smith’s doctor, we found this mutation or this  x% chance of getting some disease).  The test generates no useful information later when scientists discover that another set of mutations has a different effect.  However, when your genome is sequenced, the result is a 3 billion base pair code that defines your DNA (let’s skip epigenomic changes for now) and you can now apply new interpretations against it as those interpretations are developed.  The result is just a database, it can be carried around, emailed or stored somewhere to be mined for valuable information later (click here for a good explanation of the data set/sizes).

Again, it is unclear how the FDA would justify regulating someone knowing data about their own body if the sequencing is divorced from interpretation/diagnosis.  What if a doctor orders the sequencing, could he refuse to give the data file to you because you might misinterpret it?  One complication currently is that the data itself has some fuzzyness/interpretation to it but that should change rapidly as the technology improves.

Your Genome in the Cloud

Taken together, low cost and reusable data mean that one possible future scenario is that you have your personal genome sequence (PGS) sent to a service (a server in the cloud) that allows you to run various diagnostic algorithms against it, essentially looking at it when new credible analyses are available.  These might range from searching for a single nucleotide polymorphism to some kind of complex study of the interaction of thousands of genes.  You could have companies that will read through the DNA and write you a report, offering to pull out better and better interpretations based on the latest scientific studies.  Or maybe you just buy an app at the genomic app store and run it yourself.  Or you could sign up for a monitoring service – as new science becomes available you get updates emailed to you.

Maybe you decide to share your PGS with a million other people to allow correlations and data mining across a larger set or you share it with some personal information with a group doing research on diseases that you have a higher probability of getting.  In fact, the data may be valuable enough that these groups sequence your DNA for free in exchange for the ability to use it.

How is the FDA going to regulate analysis of PGS data when it can be located and studied anywhere?

What about privacy?

While it is not really the FDA mission, one possible factor to how WGS is used could be the privacy issue.  Can this sequence-store-analyze process be done in an anonymous manner?  Even if not, many people are sharing much more personal information on their Facebook pages so I am betting that the consumer will be OK with the usual level of IT data security for their PGS.  One more thing, doing all this yourself might be more private than having your general practitioner order the test (where it will be associated with your health records wherever they go and where insurance companies will want to see it).  A more interesting issue than what happens to PGS that you store online is what keeps other people from sequencing your genome  – seems like it would be pretty easy if they really wanted to do so, directly obtaining your DNA will be easier than breaking into a server to get it (watch the movie Gattaca if you’d like to see some ideas on how that might play out).

FDA says all options are on the table

Maybe FDA should not worry so much about DTC testing as long as the interpretation part (analysis of the PGS database) is scientifically reasonable.  The most likely effect of totally blocking DTC is just slowing US adoption of new technologies.  Instead, focus on educating the population and create some certification (or, ugh, approval process) around the sequencing and the data mining that allows the consumers to identify reputable sequencing and analysis services.

Final thoughts

I think that there are a lot of analogs here with the early development of the internet.  When the cost and difficulty of creating and moving information suddenly drops, trying to stop information at national borders or limit how people use that information generally fails.  Trying to regulate access to information only serves to hamstring a nation’s competitive forces.  What if WGS is a similarly large shift in technology from which new disruptive business models arise?  This can have huge net positive impacts on people’s lives and the economy.  The speakers at this FDA DTC meeting are absolutely right to have some concerns about the risks but I’d like to see them thinking 5, 10, 20 years out on this issue.

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