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So here we are again.

Last year, a Congressional panel met to discuss consumer genetic testing. Some of the speakers issued statements that were so factually inaccurate as to be offensive; then, they largely concluded that people should be protected from their own curiosity. This week, an FDA panel met to discuss consumer genetic testing. Some of the speakers issued statements that were factually inaccurate and in one case plain offensive; then, they largely concluded that people should be protected from their own curiosity.

When I wrote a six-part series about consumer genetic testing last year for Newsweek, I was not an advocate on either side. (At least I didn’t start out that way.) Now I find myself squarely in one camp and sorely disappointed in the way the dialogue on the issue has played out over the last few months. What motivated me to write about the issue in the first place was a feeling that consumers were being left out of a debate that was supposed to be about them. Critics in Congress and the GAO were concerned that people would mistakenly treat their necessarily incomplete genetic data sets as crystal balls, but how many customers were actually invited to the Congressional hearing to share how they might think about their results? None. This time around, at the public meeting, how many consumers were expressly invited to speak? None. It’s hard to see how people in power could ever look fairly at consumer genetic testing, given that every time they tackle the issue they end up having the same conversation without bothering to get direct input from the people whose welfare they’re purporting to protect. UPDATE: After the meeting, the FDA held an official public comment period. This was a great way to to get consumer input, and the agency should be commended for it. 

So here I am again, waving my hands and jumping up and down, trying to provide some of that input.

Last year, I was a potential consumer of genetic scans. Now I’m a current consumer. I bought a kit from 23andMe in August; when I got my SNP list back, I sent it off to deCODEme for a generously donated second opinion. And — attention, FDA! over here! — I found out something earth-shaking.

It wasn’t that I’m at dramatic risk of Alzheimer’s, which was the only bad news I thought I might get. Turns out that 23andMe doesn’t test for variants, or SNPs, in APOE4, which is the gene that could have told me such a thing. Scientists can often figure out what a genetic variant is without directly testing it, by examining other nearby variants — this is called imputation — but for technical reasons, APOE4 data apparently can’t be imputed from the information I have. The upshot is that if I’m carrying a variant that might dramatically increase my risk of Alzheimer’s Disease — an illness to which several of my relatives have succumbed — I have no way of knowing, at least not from these results.

It wasn’t that I have a very high or low genetic risk for any other common disease. Best I can tell from these results, I don’t. I suspected that already based on family history. My SNPs are just as “delightfully uninteresting” from a medical perspective as I expected them to be.

I did have two health risks that appeared in bold red text at the top of my 23andMe results list. I suppose that bold red text might have scared me if I hadn’t read the thin black text that was intended to explain it. But I had paid $500 for the thin black text. So I read it, and I reread it, and I cross-referenced it with my deCODEme report, and I clicked on the links to studies, and I did some literature searches of my own. Here is what I concluded:

(1)    For the first bold red risk — atrial fibrillation — the results were based on two SNPs. Neither by itself correlates with a dramatic rise in susceptibility. (Also, I have only one of the high-risk SNPs; my other associated SNP is actually linked to a slightly lower risk than average.) Both SNPs are in the same gene-poor region of chromosome four. Nobody knows what they do, biologically. One thing scientists do know is that other genes have been and will be linked to atrial fibrillation. None of these other genes were tested in my results. If they had been, who knows what would have shown up? It’s possible I’m not at high risk for this disease at all, especially since I have none of the known environmental risk factors. In short: I’m not terribly worried.

(2)    The second bold red risk was for Restless Legs Syndrome. According to 23andMe, 4.2 out of every 100 European women develop RLS; among those with a particular variant on chromosome six, which I have, 5.2 out of 100 will. (This in and of itself made me skeptical. More than four percent of European women have this disease? I’m willing to believe the illness is real, but might it be overdiagnosed? Why, yes, it might be.) Unlike my atrial fibrilliation SNPs, this variant is in a gene, albeit in a non-coding portion. 23andMe does an excellent job of explaining what that may mean: “The function of this gene is not yet known. Scientists do know that it belongs to a large family of genes that encode proteins that can influence activity levels of other genes. The SNP in this gene doesn’t actually cause a change in the protein sequence of BTBD9. Instead, it lies in a non-coding part of the gene where it may affect how BTBD9 is turned on or off.” In other words, I have one variant that may help regulate one gene that regulates other genes; this variant is linked to a polygenic disease for which the background rate is in dispute. Gosh! Forget Restless Legs Syndrome; isn’t this knowledge going to keep me up at night? No. No, it’s not.

These were the only two higher-than-average risks in my report. My analysis of the rest of my risks proceeded along the same lines — which were lines that anyone with an ounce of sense would follow. To wit:

Hey, I have a lower-than-average genetic risk of melanoma! Except I might not, seeing as how my 23andMe results are based on just two SNPs (does anyone think cancer is caused by two genes alone?). Given that there is melanoma in my family, and given that I’m a white girl who regrettably got burned to a crisp on a regular basis in childhood, I’ll keep wearing sunscreen.

This just in: my AA status at the SNP rs7590720 suggests I’m at “typical odds of alcohol dependence in men!” Except I might not be in real life, because alcohol dependence is not a Mendelian trait and I’m not a man.

Cool, I’m AA at rs363050! According to 23andMe, a 2006 candidate-gene study of 667 Dutch subjects showed that for each A at this site, non-verbal IQ goes up three points. But candidate-gene studies often fail to replicate. (Small quibble with 23andMe: Why cite candidate-gene studies on such a complex trait, especially in the era of GWAS? Maybe an appropriate role for regulation would be quality control, assuring that the literature cited is sound.) Besides, IQ is presumably affected by all kinds of things. This result is useful only for making jokes about one’s prowess at Sudoku, and one doesn’t need to be AA at rs363050 to see why.

What else? I’m slightly more sensitive to Coumadin than average and slightly less sensitive to Plavix. I’ll bear that in mind if I ever need an anti-coagulant — but for now, I’ll content myself with learning more about how anti-coagulants work. There’s some fascinating stuff there, starting with the fact that Coumadin was invented as a rat poison.

I carry none of the rare recessive variants that I got tested for, except for one linked to hemochromatosis. Were this a disease-causing variant, I might ask my husband to get tested, too, but my variant is mild. The only consequence of my carrying it, and finding out that I do, is that now I’m interested in hemochromatosis.

I had a blast figuring all this out. And I didn’t need a doctor to help me do it. Actually, sitting in a doctor’s office trying to sift through the data would have been less fun and almost certainly impossible, as I’m sure my primary care provider has much better things to do than babysit me while I look at PubMed.

Now that I have my results, I can’t help but laugh at myself a little, or at least at the version of myself I used to be. Listen to me back in August, agonizing over whether I really wanted to check out my own DNA: “When I finally pulled my testing kit out of its box, [I] found to my complete surprise that I was — there’s just no other word — scared of it. … Whether or not the test qualifies as a medical device under FDA rules, it looks like one. It has a biohazard sticker on it!”

Why on earth was I so scared? What was it that caused me to see my own spit as a biohazard? If you had asked me back then, I might have said something like “emotion” or “irrationality.” Now, I know that this particular type of irrationality has a name: “genetic exceptionalism.” It’s defined as “the idea that genetics must be treated as special under the law,” and it’s largely based on the unfounded belief that DNA is more powerful than it actually is, to the point of being magical.

I don’t know why genetic exceptionalism is so common and reflexive. I don’t know why so many people seem to naturally approach DNA with fear and awe. Maybe it’s because almost everyone is introduced to genetics through Mendel’s pea genes, which really were individually powerful in their effects on phenotype; maybe the lesson people subconsciously absorb is “all genes work like that.” Or maybe it’s just because of GATTACA.

Maybe it’s because DNA really is special in a number of ways. It is a biochemical form of literature, a Great Natural Novel that tells a story of life. (Not the whole story, by any means. But a good story.) It is elegant and beautiful.

But it is not magical or all-powerful, and if we are ever going to make responsible policies around it, we have to stop thinking of it as such.

Here is the earth-shaking thing I found out: It is possible to stop thinking that way. Reason can overcome emotion. People can approach information about DNA, even their own DNA — information that they might naturally find scary — and come to realize that there is nothing to fear because they see it in cold clear light for nothing more than what it is. I know people can do this, because it’s what I did.

Genetic exceptionalism is the default, the state of ignorance. How do you combat ignorance? By enabling knowledge. By giving people information and showing them what it may mean for their lives. By, say, appealing to people’s inherent curiosity about themselves, and then handing them a document that shows — that cannot help but show — that genes aren’t destiny.

This is precisely the information that bad regulation would keep out of the hands of consumers.

What will happen if we, as a society, confirm people’s misconception that genes are all-powerful, and if we tell them they are too stupid to understand their own data? They will come to believe that genes are all-powerful and that they are stupid. It’s a self-fulfilling prophecy. Whatever you think of consumer genetic testing, there is nothing that can turn up in a scan of a few hundred thousand SNPs that is anywhere near so frightening.

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12 thoughts on “DNA Dilemma: Denouement

    • Ah, Steve. I was waiting for you to show up! If you mean *my* BRCA risk, as far as I know it’s not scary at all — I don’t have any of the BRCA variants the companies test for, and I also don’t have any family history of breast cancer. (I’m aware this doesn’t mean I might not be at risk for breast cancer — I have breasts — but I certainly don’t think I’d characterize my risk as unusually “scary.”)

      Is BRCA carrier status scary for people who actually have a relevant variant? I’m sure it is. But as you yourself have noted, they can get second opinions to find out how frightened they should be, and to get medical guidance about the appropriate next steps.

      As for life and disability insurance, as anyone who has been subjected to my presence after I’ve had a few too many drinks will know, I have a lot of issues with the fact that GINA adequately covers neither. (Seriously. This is what all my conversations devolve into when I go to parties at ASHG.) But that is a problem with GINA. I think the considerable energy that’s been put into fighting DTC testing would be better channeled into working on that particular legislative reform.

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  6. Mary,

    Thank you for a lively discussion of YOUR point of view on DTCGT. I have a few problems on how you propose to solve, ahem, “genetic exceptionlism ignorance.” The model you propose is a nicely dressed up form of the deficit model of knowledge. I am sure there are many philosophers around that are cringing at the way you toss ‘knoweldge’ around as something that can easily be defined and that it can solve a complex problem so well, especially by telling others what that knowledge “means for their lives.” Knowledge in this case is intrinsically linked to how one attaches meaning AND value to what their test results mean for themselves and how it relates to their life. From the example Steve brought up about the BRCA test and what the variants may or may not mean for a woman who tests positive with a history of breast cancer in her family, I find it rather insensitive that the best rebuttal you can offer is that she should seek a second opinion on the matter and that the they will advise her on how best to proceed, or the degree to which she should be ‘frightened’. However, in a DTC model of genetic testing for ‘variants’ that may or may not be linked to the BRCA gene, it seems that a person might be a bit limited with regard to the opinions she may be able to seek, as she was most likely alone and at her computer when faced with news that has the potential to change and in some respects redefine her life.

    I have up to this point enjoyed your view and commentary on the ways in which DNA is affecting and influencing our lives; as it was limited to YOUR opinion. However, in light of very proscriptive ideas about how the rest of us common-folk can catch up to your journalistic-personal-fuelled search for the truth – I am dismayed that you could have such a poor attitude about your fellow citizens. Some of the best lines of inquiry and ability for our world to succeed the way it has are based on mutual respect for others and, especially, others’ opinions about who we are, what ideas are important to us and the many ways in which we choose to live our lives. Where the DTC genetic testing market is headed or the regulation that will shape and guide its future is anyone’s guess. But in light of my reticence to get a test, what makes my knowledge on the subject ignorant of it when compared to yours?

    • I will give you the point about philosophical definitions – knowledge isn’t being provided so much as enabled by the provision of new information that can be incorporated into existing individual worldviews. So I’ll change that word, “provided,” to something more like “enabled” or “supported.”

      But as for “proscriptive,” I have to say, I’m really confused as to how you got that out of this essay. I don’t think DTC testing is the only or even the best way to learn about genetics. It’s just one way of learning that seems to work well for some people, and I don’t think we should take that opportunity away from them. (And reticence to be tested certainly doesn’t make one ignorant! Many of the best geneticists in the world have no interest in being tested, either; I quoted one of them on that point in the original series. If you don’t want to get tested, that’s A-OK by me. Just don’t tell me I’m not allowed to — that *would* be proscriptive.)

      I don’t have a problem with people who choose to explore their results with the help of doctors or genetic counselors. (Did you read the series? I asked for my own doctor’s involvement in the mere act of choosing whether to get a test!) I just think that ought to be a choice, not a requirement.

      And God knows I don’t think everyone should be forced to take part in DTC testing or have their genetic information foisted on them if they don’t want to know about it. BRCA mutations (which have been conclusively linked to breast cancer) actually provide a nice illustration of how someone can choose the level of information she wants. The BRCA results are “locked” in 23andMe reports, so you have to expressly say, “yes, I want to know” before you receive that specific information. A hypothetical woman with a family history who gets a result while she is “alone and at her computer” does not have to be in that situation. She can (1) not partake in any genetic testing at all, (2) ask her doctor about clinical BRCA testing instead, (3) get tested for other variants DTC but opt not to find out about BRCA that way, (4) wait to unlock her DTC BRCA results with her doctor or a genetic counselor standing by, (5) get BRCA testing through DTC *and* clinical avenues (which is all I meant by a “second opinion”)… and so on. Why is it a bad thing to offer her options?

      • Thank you for clarification on the philosophical point. I would like to bring attention to the tone that I am not refuting or trying to contradict the conclusions your articles came to (and I did read them, the journey was interesting and most timely given the July hearings in front of the house of representatives), but I am more interested in the practical decisions that have to be made soon, so we can cope with what is going to come. At this time, the results one does get from the DTC test leaves a lot of room for interpretation, and for most of the public at large, it is a pretty big leap to assume they have the skills necessary to research the scientific literature and search out answers using a resource such as Pubmed. As lovely as the interpretations and explanations are that are provided by the companies, there is the sense that a conflict of interest is possible and it is not entirely a bad thing to have transparency somewhere in the testing experience. I am not advocating for a restriction of choices or the removal of options available to consumers, choice is good, but when there are no safety nets in place (or limited ones with low impact – imagine the faceless, nameless genetic counsellor on the phone), I worry that without such measures, the potential for harm increases dramatically.

        At this time, would it not be helpful if our dialogue looked beyond the personal and shouldn’t we perhaps resist making grand statements about what people are capable of based on what one’s own experience is? (“Reason can overcome emotion. People can approach information about DNA, even their own DNA – information that they might naturally find scary – and come to realize that there is nothing to fear because they see it in cold clear light for nothing more than what it is. I know people can do this, because it’s what I did.”)

        Instead, let’s offer a view of positive regulation, because in all honesty, regulation is coming and at this time, wouldn’t an effort now be better spent if we put in place mechanisms to deal with possible consequences, expand choice and the opportunity for people to seek help to make that choice and propose this with honest statements that what might be right for one person, group or society might not be right for all. For instance, the complete ban on DTC genetic testing that is in effect in Germany would not find a friendly audience in America, so what would be appropriate for an America audience or what would an appropriate form of regulation look like? And in this case, the easy answer of no regulation at all does not seem to be a wise choice either.

        Indeed, it is a sad state of affairs when the public is excluded from public meetings on issues that directly affect them. Maybe it is time for all of us to step off our soap boxes and start an honest dialogue about what can be done now so we can claim to have strained our voices shouting to enact change for a better tomorrow.

  7. I completely agree that there ought to be more discussion about what would actually constitute good regulation. (And yes, I think there’s such a thing! I don’t favor a complete lack of regulation, myself.) I can’t report on this issue right now because I’m on a fellowship that prohibits professional work; for now, I will cede the job to people like Matt Herper and Dan Vorhaus. But if you’d like to make some proposals in this space, please feel free!

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