Not enough hubris not to try to kill God

A Letter I Will Probably Send To The FDA

I predict that the current spat between 23andMe and the FDA will be less apocalyptic than some people fear. In particular, I expect 23andMe will submit a lot of paperwork, change some of their wording around, advertise a little less aggressively, stop listing some or all of their “Health Risks” and “Drug Interactions” section, and then be back on their feet in a few months.

But I’m not sure. And even that seems like a bad thing. Although I realize this is probably a very complicated legal game here, I’d like to add whatever pressure I can. So here is a letter I plan to send the FDA and maybe my Congressor once I figure out who that is. Please let me know about any factual errors, logical errors, or things I should change because they are unconvincing or offensive:

To whom it may concern:

I am writing to voice concern at your decision to ask the company 23andMe to halt genetic testing.

As a doctor, I am well aware of both the importance of genetic testing in medicine and of the difficulty in getting these tests through the normal medical system. Many of my colleagues do not know of the existence of personal genomics, and believe that genetic testing is a once-in-a-blue-moon procedure to be ordered only when there is high clinical suspicion for a rare disease such as cystic fibrosis.

Even in cases where doctors are willing to use genetic information to help in treatment, they have few good options within the standard medical system. Tests for a single mutation may cost several hundred dollars, in addition to the expensive consultation with a physician necessary to order the test and the second expensive consultation with a physician necessary to receive results from that same physician. These are rarely covered by insurance, especially for poorer patients. Patients are rarely willing to purchase these expensive tests out-of-pocket, and when they do, both patient and doctor must wait weeks for each individual result they want.

In contrast, 23andMe has raised awareness of genetics among the general population and given them questions and concerns, usually appropriate, which they can discuss with their doctor. Their doctor can then follow up on these concerns. Such followup may involve reassurance, confirmation with other genetic testing, confirmation through other diagnostic modalities, or referral to another professional such as a genetic counselor. In my experience personal genomic results do not unilaterally determine a course of treatment, but may influence an ambiguous clinical picture in one direction or the other, or be a useful factor when deciding between otherwise equipotent medications. Banning the entire field of personal genomics in one fell swoop would eliminate a useful diagnostic tool from everyone except a few very wealthy patients.

Let me give a personal example. My family has no history of any genetic disease, I (like many Americans) do not have a primary care physician, and I had no reason to go to a doctor to get an expensive genetic screening. When 23andMe began offering genetic tests through the mail for $99, the easy availability convinced me to try one out. From that test I discovered that I was, like one in every thirty Ashkenazi Jews, a carrier for hereditary sensory and autonomic neuropathy type III, a serious and often fatal neurological disease linked to a locus on chromosome 9 which can be detected by genetic screening with an accuracy of >99%.

This has given me information I need to control my future: in particular, it has made me more wary of having children with any other Ashkenazi Jew until they have been tested for the mutation as well. Without personal genetic testing services such as 23andMe, I would not have discovered this mutation; with the loss of these services, my future partner will have to convince her primary care doctor to order her a prescription version of the test. Such a doctor will almost certainly never have heard of this rare condition, may blow her off, and may charge a hefty fee for this service if they perform it at all.

In addition to these immediate consequences, I am distressed by the likely effects of this decision on genetic research. Many of the most promising medical advances in the pipeline are based on genetics, but one major bottleneck to genetic discovery is the absence of good genomes to work with. A typical genetic experiment involves using advanced software to tease out small correlations between genotypes and phenotypes. Such experiments require genotypic and phenotypic data from thousands of individuals, which is often hard to come by especially given legal restrictions. 23andMe has amassed what may be the largest database of such information anywhere in the world and is making it available to researchers (with appropriate privacy protection), an amazing public service for a for-profit company. Restricting their ability to provide this service will almost certainly delay life-saving genetic discoveries.

In contrast to these important services provided by 23andMe, your stated worries about the company are, with all due respect, somewhat bizarre. As I gather from your letter to the company, you have at least three fears.

First, you state that “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”. As I would hope the FDA is aware, it is extremely common in medicine to screen for rare conditions through affordable and noninvasive tests, with positive results followed up by more expensive, more complicated tests to confirm the diagnosis. You allow, for example, prostate specific antigen testing, even though the positive predictive value of this test at its most commonly used values is only 30%, because you correctly assume it will be followed up by further analysis before any drastic steps are taken. If the FDA believes that there are surgeons who would say “You claim to have heard you had a BRCA mutation, I have no follow-up questions, let’s schedule you for a double mastectomy”, then the FDA should be pursuing those surgeons, not genomics companies.

Second, you state that “we still do not have any assurance that the firm has analytically or clinically validated the PGS for its intended uses, which have expanded from the uses that the firm identified in its submissions”. If this means only that you are uncertain whether 23andMe’s genetic testing actually reads the genome correctly – that what it reports as an A nucleotide is indeed an A nucleotide – then I agree this is a reasonable question for the FDA to pursue. However, by your mention of intended uses “expanding”, I gather that in fact you mean the specific genetic claims they make, for example that genetics affect warfarin metabolism.

There are several thousand papers about genetics, linking specific genes to everything from eye color to intelligence to chance of developing colon cancer. Some of these papers are no doubt correct, others will no doubt in time be found incorrect. However, I worry you want 23andMe to independently validate each of these results before informing customers about them. Worse still would be a demand that the company validate the results *with its specific testing kit*. It would be cost-prohibitive even for a single company like 23andMe. It would destroy any possibility of competition; even if one company did it, new startups would not be able to. And it is unnecessary. If BRCA is linked to breast cancer in general, and 23andMe’s kit reads the genome correctly, then 23andMe’s result for BRCA will be linked to breast cancer, as will the result of any other kit that reads off the genome correctly. Asking companies to validate each result for their particular kit makes no more sense than asking each pharmacy to do independent studies to confirm that their own bottle of penicillin kills bacteria. The pharmacy’s job is to prove they have real penicillin: once they do that, the general result that penicillin kills bacteria applies.

In my opinion, 23andMe handles the complexity and uncertainty of genetic testing entirely correctly. It rates each of its tests on a “confidence” scale showing how much consensus there is in the literature that the result is correct and gives a clear explanation of what each confidence level means, citing all the studies it uses to gather data. It states very clearly on every single page that its results are open to interpretation and should not be used to unilaterally guide medical treatment. On results with less than its highest level of confidence, it refuses to even give numbers out of a fear that these might seem unfairly authoritative, only linking to the appropriate study and allowing consumers or their doctors to draw their own conclusions.

Third and most important, you state that “assessments for drug responses carry the risks that patients relying on such tests may begin to self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome of the assessment”. For me, this is the most worrying objection, because it seems to acknowledge that although 23andMe may provide accurate information with the appropriate disclaimers, merely giving patients access to medical information is itself dangerous.

I agree that this can sometimes be true. For example, when I was in medical school many of my classmates came down with so-called “medical student syndrome”, in which their increased awareness of symptoms and diseases made them more likely to believe they had some rare and dangerous syndrome, causing unnecessary pain and sometimes even doctors visits and lab tests.

But the alternative is banning all information that anyone could possibly use to evaluate their own health. I have even heard the tongue-in-cheek proposal of banning medical textbooks. You worry that if a patient learns their genetic susceptibility to warfarin it may convince them to alter their own warfarin dose without a doctor’s input. But the same is true if a patient learns the (true) fact that leafy green vegetables affect warfarin levels, or that women require less warfarin than men – facts that can be discovered in any book about medicine or pharmacology. Likewise, knowing one’s weight may convince someone to take unsafe diet pills, to starve themselves, or for that matter to adjust warfarin dosing – the clearance of anticoagulants appears to increase with weight. But banning people from weighing themselves without a prescription is neither clinically nor ethically sound.

The two consistent options are to work to ban patients from learning any accurate information that might be relevant to their health – exactly the opposite of ethical medical practice – or to trust patients and doctors to work together to use information responsibly to support their own care, whether that information comes from a bathroom scale or a genetic test.

In conclusion, while I am excited about the possibility of the FDA helping patients and doctors by vouching for the accuracy of the general process that personal genomics services use to read the genome, I am extremely concerned that it may go beyond this useful service to place unnecessary or impractical restrictions that shut down the field of personal genomics entirely and prevent individuals and medical professionals from getting inexpensive, simple, and unrestricted genetic testing. I urge you to continue negotiating with 23andMe and to take every step possible to ensure that their important service returns to the market as soon as possible.

Thank you for your time.

Yours,
Scott [Alexander], MD, BCh, BAO

Sort of wondering whether I should cite sources for claims like HSAN3 being detectable with genetic testing or warfarin metabolism changing with weight. Is it considered appropriate to have a references section in a letter to a congressional representative? Inappropriate enough to counterbalance the level of awesome?

EDIT: Looks like there’s a petition to sign.

EDIT2: Madeleine Ball points out the less immediately sexy but ultimately equally important issue of the NIH Genomic Data Sharing Policy, which would affect some of these same things but is getting a lot less press.

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96 Responses to A Letter I Will Probably Send To The FDA

  1. Tristan says:

    Outstanding letter and I share your concerns. One avenue that may be worth pursuing to increase exposure would be to have the letter published as an open letter somewhere. Although possibly it is to long for most mainstream publications. And of course it might compromise your pseudo-anonymity…

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  2. Pingback: A Letter I Will Probably Send To The FDA (on 23andMe) | Enjoying The Moment

  3. David says:

    Excellent letter :)

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  4. mo says:

    Don’t send it “to whom it may concern”; send it to Alberto Gonzalez, the individual at the FDA who sent the letter to 23andme.

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  5. Scott, if you’re interested in genetics regulation, please consider looking at our public comments on the NIH’s draft Genome Data Sharing Policy: http://blog.personalgenomes.org/2013/11/21/pgp-comments-on-genomic-data-sharing-policy/

    This policy will affect all participants in US funded biomedical research — $31B annual funding. Surnames can be predicted from Y chromosome data but the NIH persists in calling the data “de-identified” and is about to *require* all participants in their studies have their genetic data broadly shared.

    23andme is well-funded and has plenty of opportunity to defend themselves, and plenty of voices are raised already. My thoughts are aligned with Matthew Harper at the moment: http://www.forbes.com/sites/matthewherper/2013/11/25/23andstupid-is-23andme-self-destructing/ In contrast, there almost no voices raised to represent the numerous participants in NIH’s studies. With so few people noticing the issue, your voice could be a powerful one.

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    • Scott Alexander says:

      I’ve added a mention to the main post and will look into this more. Can you think of anything specific I can do to help?

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      • Maybe write a separate post about it that helps explain it to others? I’m hesitant to take the professional risk (or risk to the PGP) by writing more bluntly than we already did, but I could share something you write.

        Our public comments are hard for folks to read, but I think the issues are ultimately quite simple. Genomes are increasingly identifiable and reveal information about yourself that you might not even be aware of. The NIH needs to clearly acknowledge this and all this entails.

        The second point is also worthwhile and follows from the first — it’s not fair to require all participants agree to share such revealing and identifiable data but NOT require they have access to it themselves. Besides, such access could result in a lot more data sharing if some participants later donate that data to other projects.

        The NIH’s official “comment period” for the draft ended last Wednesday but I think kicking up a bit of fuss at this point (immediately following our comments) could get them to pay attention to what we recommended.

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    • Douglas Knight says:

      How are you aligned with Herper? Your statement (“well-funded…plenty of voices”) seems to be exactly opposite to his: “But outside of a crowd of libertarians and genoscenti, the company does not have the political support it needs for a fight against the FDA.”

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      • Madeleine Ball says:

        I’m trying to say: if you’re looking for effective and important policy issues, it may be more worthwhile to pay attention to the other issue I am raising.

        23andme is a commercial company, they can afford lawyers. My personal opinion is that it sounds like they screwed up if they let six months lapse without communicating with the FDA (a.k.a. “the single largest existential threat to your business model”). I enjoy 23andme’s product and appreciate that pushing back on the FDA may be valid, but I’m finding it hard to sympathize with 23andme as some sort of bedraggled underdog … I mean… six months? Really?

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  6. Anonymous says:

    Genetics PhD here (not that it’s particularly relevant to this letter). Agree totally.

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  7. Julia says:

    Does including citations make you look more or less like a crank to the overworked Congressional aide who reads your letter, given that they get a lot of letters from cranks? I’m not sure.

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    • ozymandias says:

      IME volunteering for a congresswoman, the overworked congressional aide just notes down on a form that you got a letter about Topic Y. Presumably if enough people complain about it the congressperson is like “ah! This is clearly a topic of concern to my constituency!”

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      • Alexander Stanislaw says:

        If this is true then every American reading this who cares about the cause should probably send a letter as well even if its not as compelling as Scotts.

        I may draft a few versions of such a letter and try to convince my friends to send it to their congressional representative (since I am not American but am currently living in the US). This does sound important to me.

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      • Alexander Stanislaw says:

        What are your thoughts on mo’s suggestion: send the letter to Alberto Gonzalez rather than a congressional rep? Would that be more effective?

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      • ozymandias says:

        I have no idea; all I can speak about with authority is what happens to letters that come to one particular regional congressional office. That said, I think that writing letters to your congresspeople about issues you care about is fairly useful, even if you are not eloquent or qualified.

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      • Said Achmiz says:

        IME also working for a congressperson, this is accurate. The specific content of letters is rarely conveyed to the congressperson directly.

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  8. MugaSofer says:

    “However, I worry you want 23andMe to independently validate each of these results before informing customers about them. Worse still would be a demand that the company validate the results *with its specific testing kit*. It would be cost-prohibitive even for a single company like 23andMe. It would destroy any possibility of competition; even if one company did it, new startups would not be able to. And it is unnecessary. If BRCA is linked to breast cancer in general, and 23andMe’s kit reads the genome correctly, then 23andMe’s result for BRCA will be linked to breast cancer, as will the result of any other kit that reads off the genome correctly. Asking companies to validate each result for their particular kit makes no more sense than asking each pharmacy to do independent studies to confirm that their own bottle of penicillin kills bacteria. The pharmacy’s job is to prove they have real penicillin: once they do that, the general result that penicillin kills bacteria applies.”

    This section seems like it could be clearer? Maybe go over the wording.

    Nice use of the “proving too much” argument with the “ban weighing scales now” bit, incidentally.

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  9. Randy M says:

    “Tests for a single mutation may cost several hundred dollars”
    This jumped out at me as a Dr. Evil moment (from the Austin Powers movie). Does anyone in the medical industry bat an eye about ordering a test costing merely hundreds of dollars?

    (This is not just general cynicism. My wife was told by a technician for a leg sonogram that the test was more or less just to pad the bill, as the chance of a blood clot related to her treatment or condition was so low. And seeing the cost of some just-in-case colonsocopies, MRI, etc.)

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    • Scott Alexander says:

      No one in the medical industry would bat at ordering that test, but if there’s not some obvious specific indication for it insurance won’t pay, and then you will have to pay those hundreds of dollars out of pocket.

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  10. Alexander Stanislaw says:

    I’d sign the petition if I were Americans. I thought it was very compelling, the strategy of opening up with your credentials and giving personal anecdotes before giving statistics seems like a good one.

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  11. Martin-2 says:

    “A typical genetic experiment involves using advanced software to tease out small correlations [...] across thousands of individuals. Such experiments require genotypic and phenotypic data from thousands of individuals”

    Hundreds of individuals. Got it.

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  12. Pingback: Genome (DNA) Sequencing/Analysis - Page 6

  13. Engineer says:

    As someone who suffers every day, because the drug that would cure my illness, a drug that is proven safe in clinical trials, is not on the market because the FDA makes it too expensive to go thru the hassle…. I hope you will send that letter.

    And then I hope you will realize that sending that letter is pointless.

    You’re a doctor, you’re a professional in that field. They couldn’t care less what you think.

    They will not change until enough people start voting libertarian and start standing up for our right to determine our own health care in consultation with our doctors.

    So long as people like you vote republican or democrat, it’s people like you who keep the drug I need out of my hands, as much as the FDA.

    The FDA needs to be shut down.

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    • Scott Alexander says:

      On the one hand, I sympathize with you.

      On the other hand – yesterday one of my patients came in with a very fast heartbeat, covered in sweat, complaining of feeling hot all the time – classic symptoms of hyperthyroidism. Took thyroid hormones and, sure enough, they were really high.

      Story was, a few months before she’d been feeling a little tired so she’d gone to the doctor to get a thyroid test done (low thyroid levels can cause tiredness). The doctor said the test was perfectly normal. She decided that wasn’t good enough and went to a “holistic practitioner” (read: quack) who did a “holistic thyroid test” (read: made up some numbers and told her she had thyroid deficiency so he could sell her drugs). Then he diagnosed her with low thyroid and gave her thyroid hormone.

      Well, when you don’t have low thyroid and you start taking extra thyroid hormone, you become hyperthyroid, which she immediately did. Luckily it got caught before something really nasty happened. On some questioning, she admitted the reason she had been feeling a little tired lately was that she was working twelve hour days.

      So it’s a toss-up. Sometimes the FDA are idiots and ban useful and important things. Other times I wish they’d be a little more proactive in banning things that are totally fake and kill people.

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      • Douglas Knight says:

        What did the guy do, exactly? Surely making up numbers is already illegal? So what can the government do to stop him? Do you have a concrete suggestion?

        It’s a lot easier to tighten up rules at a bottleneck where people come to FDA, like new drug applications. So that’s what they do, rather than seeking out more diffuse but clearer violations.

        A completely different problem is Ranbaxy, caught faking test, what, 10 times? Yet no cumulative punishment. I don’t understand what happened there, but I think it shows limits to bureaucracy.

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  14. dan says:

    A well crafted letter with excellent arguments.

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  15. CP says:

    Not that I believe a reply from a potential internet crank would sway you from your convictions, but this letter is really misguided, and speaks to a pretty significant misunderstanding of the point of clinical laboratory testing. With precious few exceptions, lab testing should be used for sick people. The example you gave of how you interpreted your own findings only emphasizes this point. Notwithstanding the issue of whether or not they actually got the result right, the finding of a rare allele in a normal person is really troublesome. In your case, had you found another Ashkenazi Jew later in life and were thinking about kids, the guidance today from genetics bodies is to test you and your partner for the common Ashkenazi mutations anyhow, so getting this result now has done little other than interjecting a potentially stressful issue into your future relationships. I might add that your chances of having a kid with the disorder in question with a random Ashkenazi partner are less than 1:100, even if you truly carry the allele (1/4 because autosomal recessive times prevalence).

    As to whether or not people act on 23andMe results in vacuo, the answer is yes, they do. That you have not seen it makes me wonder what type of practice you have. I run a clinical laboratory (I am a clinical pathologist), and I deal with the sequelae of follow ups to unnecessary testing all the time. Remember that mastectomy is not the only possible adverse outcome from a BRCA1/2 test. Additional testing is itself unpleasant, stressful, and expensive, and globally (not just in one docs experience) these cumulative costs to our patients far outstrip the 99 bucks they pay upfront.

    What the FDA is doing here is a great first step, and I hope they continue with the other labs that are plaguing our diagnostic landscape with non actionable testing. I have talked to Alberto Gonzalez about this at a meeting, and believe me, he has heard everything you are saying from many other people. At his level, though, he has to make decisions that put the interests of the whole society ( who are collectively hurt by places like 23andMe) over the interests of a few individuals like you (who mostly don’t really understand how lab tests are performed or correctly interpreted).

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    • Doug S. says:

      Scott’s medical specialty is psychiatry.

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    • Scott Alexander says:

      I agree that there are some truly awful lab tests (see my story about thyroid above). But these aren’t them.

      As you probably know, there’s actually a very large amount of very appropriate population screening of healthy people going on. Just to name ten things off the top of my head in ten seconds that are highly recommended, PKU, cholesterol, hypertension, glucose, mammography, colonoscopy, pap smear, depression, PSA (admittedly a stupid idea), and Down’s Syndrome.

      You accuse me of not being familiar with lab testing, and you might be right, but clinical practice has its own set of pitfalls. Like, you know how it’s recommended that all Ashkenazi get tested for genetic diseases before marriage? I can’t find good stats on what percent of young people have a regular doctor, but my guess is it’s around 50%. Certainly the people who come into the emergency room for their flu because they can’t find a PCP who will accept their insurance don’t. And what percent of primary care doctors do you think know which of their patients are Ashkenazi, remember the factoid they heard once in medical school that Ashkenazis need genetic testing, and remember to ask their Ashkenazi patients this when they hear that they’re getting married?

      (as an anecdote, I am a full-blooded Ashkenazi Jew, I have great insurance, I work in a hospital surrounded by doctors all the time, I have been fascinated by genetics my whole life, and I probably would not have gotten this test before marriage if not for 23andMe. What chance does anyone else have?)

      (also, contrary to your “you shouldn’t get it now, it’ll just make you worry” point, Dor Yeshorim suggests people do it on the third date so that if they end up with the same recessive gene as their date they can decide whether they want to continue seeing that person before they’ve Fallen Madly In Love With Them. Third date sounds probably suited to an Orthodox Jewish culture where relationships usually end in marriage, for seculars I would suggest ASAP so that people can compare results as soon as possible in the dating process)

      Yes, thank you, I graduated from medical school with highest honors in genetics and I am aware of what “autosomal recessive” means. On the other hand, I expect to have two to three children, raising my chances to 2-3%. I do not think that a 2-3% risk of my child dying a horrible death before my eyes is something I can dismiss so quickly, and if you will look down one or two posts here you will see this is an area of special concern to me.

      I don’t entirely get your point with the BRCA example. Suppose that (as you seem willing to grant) 23andMe accurately reads DNA. That means if it says you have a BRCA1 mutation, you have a BRCA1 mutation. The chances of getting breast cancer with a BRCA1 mutation are 60% (not 60% more, 60% full stop). If you see on 23andMe that you have BRCA1 mutation, then you going and getting lots more tests is A VERY GOOD AND IMPORTANT THING. Even if 23andMe has a positive predictive value of only 10%, something I have never heard them accused of even by their worst enemies, then people whom 23andMe says have BRCA1 getting lots more tests is a very good and important thing.

      In fact, quick back-of-the-envelope calculation. 1/500ish people have the mutation. 23andMe has 400K customers. That means 800 BRCA mutations detected. Halve it to take out men, then double it back b/c Ashkenazi Jews probably disaproportionate 23andMe customers. Depending on what percent of those people didn’t already know and what percent follow up on that result by getting the official confirmation test followed by treatment, probably hundred or so lives saved there.

      I agree that for every person who discovers she has BRCA, there are ten people who find out they have 1.1x the average risk for heart disease and freak out and demand a coronary bypass surgery. There is a simple and helpful response doctors can give these people. That response is “No.” If they demand some sort of fantastically expensive radionuclide scan: “No.” If they demand to have their cholesterol checked and ask for advice on diet and exercise: “Well, finally. I thought you’d never ask.”

      (This is also what doctors do when patients demand radionuclide scans because they heard about a rare new virus going around on “Dr. Phil”, and in two thousand other cases)

      And it may not be especially important today as we can only predict heart attack risk in the most general terms, but in 20 years, we’re going to know more genetics. And the battle that’s being fought now is whether people are going to have access to that information in a simple, easy-to-get and easy-to-understand format, or whether they’re going to have to go through a lot of trouble and expense to get it that pretty much limits it to wealthy people or hobbyists.

      There’s an even more important component to the issue, which is the level of FDA regulation that genetic tests have to meet, and in particular whether each test needs a separate approval. See Phil Goetz’s comment here for why I think this is super-important and the 23andMe incident sets off huge alarm bells.

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      • Douglas Knight says:

        1/500ish people have the [BRCA] mutation.

        Where do you get that number?

        The mutation that 23andMe tests is 1/100 Ashkenazi and no one else. Maybe 1/500 people have a thoroughly broken BRCA, though that sounds way too high to me. 1/100 Dutch (eg, Angelina Jolie) have a different mutation that it would be reasonable for 23andMe to add to v4, and all other variants are unique.

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        • Douglas Knight says:

          As of about 11/2012, they had 136 BRCA hits out of 150k customers (although some of those customers had earlier chips that didn’t test BRCA). That suggests 9% Ashkenazi, similar to the 7.5% in 6/2011. Extrapolating to 3x customers today, that’s 300 hits, half of them women.

          (Some caveats: (1) There is an extra filter. That’s not 136 people whom the computer knows to have a broken BRCA, but only those who clicked the “unlock BRCA results” button. So the effective customer base is lower and that rate of hits and thus Ashkenazi is higher; (2) If you’re a carrier, you should have your relatives screened, which could greatly elevate the 23andme rate. But the implication is that people have their relatives screened by Myriad, not 23andme.)

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    • Scott Alexander says:

      “I have talked to Alberto Gonzalez about this at a meeting, and believe me, he has heard everything you are saying from many other people.”

      It is somewhat difficult for me to believe this as the name of the FDA official involved is actually Alberto Gutierrez, and the name “Alberto Gonzalez” was just an error made by another one of my commenters who posted above you which you apparently copied. Apologies if I am being unnecessarily paranoid.

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  16. > In my experience personal genomic results do not unilaterally

    Missing comma after experience.

    Your logical-consistency slippery slope argument (if you ban 23andme, you must also ban bathroom scales), is true but perhaps less convincing than other ways that could be argued.

    I would reframe that as a precedence argument, both invoking the ethical precedence that medical info is cleared for consumers, and urging the authorities to consider precedence effects of this regulation.

    Also, be sure to back up the abstract argument with the specific argument for this case. It should be easy to show that the expected benefit of the true-positive test is greater than the expected harm of the false-positive, and this would prevent any counterarguments along the lines of “never mind precedent; in this case it should be banned”.

    I urge you to raise a public stink about this aimed at the public and more general in scope. FDA idiocy is a bigger problem than just 23andme.

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  17. Douglas Knight says:

    This reminds me a comment Phil Goetz left on this blog, probably too late for many to see it.

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  18. Excellent letter, polite and well argued. I urge you to make it an open letter as well as sending it to the FDA – actually it’s already partly open, I came here through HN rather than my usual bookmark, but posting it to your blog is not quite the same as sending it to a newspaper. At any rate you have very little to lose by trying to get it published as widely as possible.

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  19. Error says:

    > “But the alternative is banning all information that anyone could possibly use to evaluate their own health.”

    This part feels like the fallacy of the excluded middle to me. You could, for example, ban some information that you think is more likely to result in patient stupidity and allow other information that you think is less likely to result in patient stupidity. It might be a dumb alternative but it is an alternative. I wouldn’t be surprised if a recipient caught that and dismissed the rest of the argument based upon it.

    The rest is fantastic, though I have my doubts about whether anyone in a position to do anything about it will ever actually read it. (and a paranoid would have doubts about whether their stated reasons for this action are their actual reasons; in which case they may not be subject to argument anyway)

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    • Scott Alexander says:

      “This part feels like the fallacy of the excluded middle to me. You could, for example, ban some information that you think is more likely to result in patient stupidity and allow other information that you think is less likely to result in patient stupidity. It might be a dumb alternative but it is an alternative. I wouldn’t be surprised if a recipient caught that and dismissed the rest of the argument based upon it. ”

      It’s a good point, but if we tried it what would actually happen is that we banned information that had bad lobby groups or needed an IQ above 80 to understand, and allow information that was traditional or had special interests behind it or would make stupid people angry if it got banned.

      I don’t want to be quite that honest when writing my congressman.

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  20. Nestor says:

    Peter Watts puts references in his science fiction novels. It’s kinda badass.

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  21. Watercressed says:

    If you’re addressing the FDA, you need to mention the biggest reason that this letter was sent: 23andMe filed initial paperwork, the FDA asked for further information, consistent with regulations, and then 23andMe did not do anything for several years.

    I’m pretty sure that this letter is entirely consistent with regulatory law. The FDA does have discretion, but at some point, they have to enforce what’s written. The letter lists many good reasons why this decision is damaging, but the FDA can’t say “this product sounds like it has positive effects, so we’ll allow it”.

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    • Scott Alexander says:

      Yeah, I agree. I said that I understand why FDA is doing it, I hope they do a good job in ensuring the test accurately reads the genome, but I’d be disappointed if they went much beyond that.

      I am pretty clueless (and curious!) in what’s going on behind the scenes here. 23andMe is either INCREDIBLY dumb (uncharacteristic of them) or has some angle to get publicity or decrease public trust in the FDA or something. Even knowing that I feel pretty okay going along with them.

      Report comment

  22. Phillip says:

    Congressor is not a word.

    Report comment

  23. Alex Mennen says:

    A piece of advice I’ve heard for sending letters to members of Congress is to ask that they provide a detailed reply about your concerns, and that the reply not be a form letter. Congressional offices usually oblige such requests, and it will force the intern who has to read your letter to think about it more, and to figure out what the Congressperson’s position is, which will increase the chance that it gets brought to the attention of the Congressperson if they don’t already have a position.

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  24. Chris B. says:

    I was with you 100% until I read this article from the Standford Law Biosciences Blog, particularly this quote:

    “The SNP chip method that 23andMe uses was never very good at providing useful genetic information. Its advantage has been its low cost. But as sequencing gets cheaper and cheaper, SNP chips have already largely become obsolete for most genetic testing. Don’t look only for SNPs, do a whole exome (the 2 percent or so of the genome that “codes” for protein) sequence for under $1000 or a whole genome sequence for under $5000 (today – under $1000 soon).”

    Can you speak to this for those us who are not well-versed in genomics?

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    • Douglas Knight says:

      Consumer exome or genome sequencing isn’t really available at the moment. Lots of false prices are advertised. I think $5000 for exome or $20k for genome is more realistic today, plus a lot of work to find someone actually selling the service.

      It is certainly true that 23andMe’s product will be obsolete in a few years, but this has nothing to do with particular products; this is all about information. The same issues apply to 23andMe interpreting complete sequence data. The FDA specifically mentions BRCA. Currently, 23andMe detects the particular mutation that 1% of Ashkenazi have (and a couple that 0.1% have). Moving to exome will let them detect the form that 1% of Dutch have and much rarer forms, but it won’t change the usefulness to Ashkenazi women.

      Report comment

      • If you’re looking for consumer exome or genome sequencing, I think DNA DTC might be promising. I don’t know them personally or work with them, but I heard they were advertising at ASHG and so I’m passing them along as a lead. http://dnadtc.com/

        I thought their terms & conditions were interesting. They’re very strong on stating that it’s “research use only” — research-grade data.

        Report comment

        • Douglas Knight says:

          The prices are $7k for genome and $900 for exome. They offer a SNP chip that looks slightly inferior to 23andMe’s, at twice the cost. Pretty close to the quoted numbers.

          The prices look much more real than anything else I’ve seen, so I retract my numbers, but I’m not entirely convinced it’s real.

          Report comment

      • b says:

        23&me offered exome sequencing to their subscribers for a while. IIRC, for $1k you’d get a a PDF summary, a VCF file and a BAM file.

        Report comment

    • AlexSchell says:

      SNP microarrays provide much less info than sequencing (whether exome or genome). Basically a SNP microarray gives you a list of which sequence variant you have, at each of a few hundred known, interesting places like the BRCA gene. Sequencing gives you the entire exome (all coding regions) or genome, respectively. Sequencing obviously gives you a broader picture, but the short-run advantages are in areas where the science is less settled. Notably, if you read about some SNP that was newly discovered to correlate with something of interest, you can pull just up the website and check your status.

      None of this in any way supports the FDA’s proposed action. The FDA’s absurd clinical validation requirements for 23andMe’s microarray product would apply equally to their or anyone’s sequencing products. If the FDA gets its way, it will cripple personal genomics in its current form. There are workarounds I can think of, but the effect on innovation will obviously still be negative. If you want progress in personal genomics, you should be against the FDA on this one.

      Report comment

  25. CP says:

    One other thing…focusing at all on the indications or idea of direct to consumer testing is missing the point of the FDAs action. 23andMe didn’t follow the simplest of rules for test validation that all of is in the clinical lab have to follow. Their lab should be shut, like mine would be if I did the same thing.

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  26. Jonathan Weissman says:

    Are you trying to convince the FDA to ban bathroom scales?

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  27. Somehow or other (a $99.00 fee) is probably scaring the bejeebzies out of Big Pharma, not that their advertising is too aggressive. They need better and more obvious disclaimers as to what the test can and cannot do. Certainly a niney-nine dollar test cannot do what a $10,000 test can do. OR CAN IT? Eventually this is what it will cost and if so the cost/benefit equation is very significant, indeed !

    Report comment

    • Douglas Knight says:

      Most genetic test that cost $10k are completely different and not covered by 23andMe. If a genetic test costs $300, it is probably a subset of the $100 23andMe test. I believe Ashkenazi carrier panels are a subset of the 23andMe test. Usually they cost $2k, but sometimes they cost $10k.

      But that doesn’t mean that you should ever pay $10k for a genetic test. It is almost always better to get an exome or genome sequence for less money.

      Report comment

  28. Charley says:

    hey everyone i am so glad that i found help that make me to conceive i am really pleased with this spell caster i found online that cast a spell pregnancy spell for me that make me to conceive and in few week now i will have my child. i have been married for many years without a child but with the help of Dr.Odogbe i came in contact with online was able to help me with his pregnancy spell. i want to appreciate everyone that has recommended Dr.Odogbe to us online if not for you all i don’t believe i would have found this great help Dr.Odogbe has render to me and my partner. in case anyone out there still need his help to conceive just reach Dr.Odogbe via his email address anoitedtemple@gmail.com indeed Dr.Odogbe is now our solution to have our own children.

    Charley
    USA

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  29. Anonymous says:

    I HAVE FOUND A SPELL CASTER WHO HELPED ME WITH A FERTILITY SPELL AND HELPED ME HAVE MY OWN BABY. IT ALL HAPPENED WHEN MY HUSBAND SENT ME PACKING FOR NOT ABLE TO GIVE HIM A BABY AFTER MANY YEARS OF OUR MARRIAGE. I ATE DIFFERENT PILLS AND NOTHING HAPPENED UNTIL A FRIEND INTRODUCED DR.ODOGBE OF anoitedtemple@gmail.com TO ME WHO ALSO HELP HIM GET A CHILD. HE CAST A SPELL FOR ME AND I GOT PREGNANT FEW WEEKS LATER, IF YOU NEED HIM ASSISTANCE, HIS EMAIL IS
    anoitedtemple@gmail.com

    Report comment

  30. MADALENA says:

    i have been married for the past 12 years without having my own child this was really killing me and my husband but i came across this Doc online Dr.Odogbe he is a spell caster i contacted him to help me out with his spell behold after he cast the spell for me i started seeing my periods and after a week i became pregnant to the glory of god i have my own twin baby boy. please in case you are reading this please help me to thank Dr.Odogbe of anoitedtemple@gmail.com for the grate help he render to 12 years of marriage. or incase you his help just contact him via his mail anoitedtemple@gmail.com

    Madalena

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  31. Miley says:

    My name is Miley, i ‘m here to testify on how i was able to conceive and have my Baby girl after 5years of marriage. with so much much joy in my heart i want to thank Dr.Odogbe whose email address is anoitedtemple@gmail.com , Dr.Odogbe did a pregnancy spell for me after i contacted him to help me out in my marriage i explained to him how i have so many miscarriage 2years back. i spent $200 for him to cast the spell for me and after he cast the spell he told me to sleep with my partner and after i have done as he told me i went for a pregnancy check up a 2week latter and i found out i was pregnant to make my story short i gave birth to a baby girl this year September 15th 2013. all thanks to Dr.Odogbe, i will also recommend him to help you out you can reach him via his email address anoitedtemple@gmail.com .

    Miley

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  32. Someday says:

    It sounds strange for you to say that a potential future partner of yours will have to convince her primary care doctor to write a prescription for a genetic test. If you are a doctor, why can’t you write her a prescription for free?

    Report comment

  33. Pingback: FDA orders 23andMe to shut down home genome test - Overlawyered

  34. LRS says:

    For years, my husband and I struggled to conceive. I consulted renowned spellcaster Dr. Odogbe, who took my bank account information and then cast a pregnancy spell on me. Within a month, to our tremendous joy, we discovered that I was pregnant. But it wasn’t until a routine first-trimester ultrasound that we learned of the terrifying and awesome extent of Dr. Odogbe’s power; eight fertilized embryos had implanted. My husband and I were stunned. We were neither financially nor emotionally ready to care for octuplets. We spent days tearfully discussing our options. We just couldn’t handle eight children, especially given the near certainty of premature births and the concomitant crippling medical expenses, and yet, it had taken us so long to conceive and we were terrified at the prospect of having to start over.

    The strain on our relationship became more evident over the following weeks. My husband had never been a violent man, but he began lashing out in ways that scared me. He took up drinking and frequently came home at 4:00 AM reeking of whiskey and vomit. One night, I received a phone call from the police department, informing me that he had been arrested for disorderly conduct and that I needed to come to the police station so that he could be released into my custody. As I stepped into the holding cell and looked with heartbroken eyes upon the broken shell of a man my husband had become, I heard a commotion behind me. I turned around to see the officer who had taken me to the cell, a pleasant, round-faced young man…lying prone on the cold concrete floor, at the feet of a sinister and imposing figure clad in a white lab coat.

    It was Dr. Odogbe.

    Thousands of thoughts raced through my mind as the doctor began waving his hands and chanting, undoubtedly casting another powerful spell whose nature I could not even being to imagine. I stood, frozen in terror, as the air around Dr. Odogbe began to swirl and crackle. But then, my husband, roused from his drunken stupor, charged past me and tackled Dr. Odogbe, seizing him around the waist and wrestling him to the floor. The spell was disrupted.

    “Honey!” my husband shouted at me. “Run!”

    I rushed out the door of the cell, down the hallway, and out the door of the police station. But when I reached my car in the parking lot outside, I was horrified to see a man sitting in the driver’s seat, wearing a white lab coat. It was Dr. Odogbe.

    My eyes wide in terror, I stumbled backwards as he stepped out of the car and began to wave his hands and chant. I ran back into the police station and locked myself in an office, where I’m currently sitting and typing this. But right outside the door, I can hear the air swirling and crackling, and I know that it’s Dr. Odogbe. I don’t know what’s going to happen to me or why I’m the target of his arcane malice. I just wish I had never sent that email to anoitedtemple@gmail.com (sic).

    Report comment

    • JRM says:

      I’m for deleting most of the spam above, but you have to keep one to keep this, which was by far the most plausible account given for Dr. Ocatpee.

      Report comment

    • Olumide Odogbe, Archmagister of the Order of Atlantis, Wizard of the Ninth Circle, MD says:

      The fools among you curious about the fate of the girl will enjoy learning that she no longer walks the Earth of her own will and her soul, safely ensconced in a psychoactive crystal, is now in my possession. It, alongside many others, shall die in the grand ritual to come but do not lament her, as thus she will play a pivotal role in bringing about the new world order — surely, a fate worthy of the deepest envy!

      For years now, I have labored. Since the youngest age I have seen things, ghostly shapes, eerie presences, swirling patterns of energies from a layer of reality beyond mortal sight. They laughed at me. They called me mad. But I never cared. I sought out lost wisdoms, uncovered ancient secrets. I tread confidently and with purpose where others had stumbled. And as I grew in power, the shape of my destiny revealed itself. Disconnected bits of lore coalesced into a grand whole, giving me powers far beyond those of mortal men. Patterns of forgotten histories correlated, showing paths to buried treasures. Plans were formed, efforts were made. And now it is all coming to fruition!

      The children that I have gifted to desperate women throughout the years shall arise to serve their true master and become an unstoppable force for conquest. The collected souls shall be extinct, the explosive force of their agony ripping apart the veil between worlds, and on the longest night the flying city of Atlantis, hidden for millennia in the space between worlds, shall arise once more. And sitting at its throne will be me, to rule humanity as its new God!

      But still, there are patterns of destiny which precise shapes elude me. The prophecies I’ve gathered speak of a third party, an individual who shall affect events with great potency and be a lynchpin upon which the fate of the world will turn. I have been observing you for a long time, Scott Alexander, and I believe you to be that individual. I am making an offer to you. Join me and swear fealty and you shall be rewarded greatly. Oppose me, and face swift defeat.

      Make no mistake, Scott Alexander, your destiny shall serve mine. Your choice is to embrace is or to be crushed in a futile struggle. I shall contact you soon, through means beyond your wildest imaginations, and I trust you to make the wise choice.

      Report comment

  35. Anonymous says:

    > hard to come by especially given legal restrictions.

    This needs a comma.

    Report comment

  36. Doug S. says:

    The spambots are evolving.

    Report comment

  37. Martha says:

    I just told my grandparents about my liason with Dr. Odogbe.

    My grandma thinks I’m confused and don’t actually feel any MAGICAL tendency to conceive. She is basically in denial.

    My grandpa didn’t understand a think even though I explained the same things to him over and over again. Even after an hour long talk, he still thinks a witch doctor is some creepy dude who speaks in tongues. There is literally something blocking his mind.

    It’s the same with my parents. They give up after two hours, tell me to leave them alone because “it’s very difficult to understand and they are tired”. I ask them if they understood everything I said, and they say “yes”. The next week, they are worried again and think I’m some kind of sicko.

    They are all mentally ill.

    Report comment

  38. DSmith says:

    WONDERFUL letter! On behalf of the half million who have already submitted tests to 23andMe, I applaud you. Your letter put into words my exact thoughts regarding genetic testing.

    I understood from the start that the science of genetics is in its infancy – and as much as I find my own results interesting, I realize there are many variables and much to be discovered. I do not hold 23andme accountable for my results, nor was I alarmed by my “risks.” Today, I consider 23andme to be a simple tool among many. But to future generations of my family, having access (and advanced science) to their long gone relative’s genetics information will be considered a gift.

    Please, send your letter.

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  39. Pingback: The Amazon whisperer, invisible interfaces, FDA vs 23andMe, and robots usher in a new polical order - O'Reilly Radar

  40. Jonathan says:

    Genetic disease screening for is actually fairly routine with Ashkenazi couples because we’re so very inbred. I’m not entirely sure that HSAN3 is on the standard battery, but if so it may not be the best example for the FDA.

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  41. jaimeastorga2000 says:

    So… this post caught the attention of Mencius Moldbug.

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  42. JP H says:

    A counter point considering why the tests are so cheap…to aggregate data and sell it on.

    http://www.scientificamerican.com/article.cfm?id=23andme-is-terrifying-but-not-for-reasons-fda

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  43. Pingback: The internet mystery puzzling the world | EveryBenefitThings

  44. Pingback: From the Archives: 11/26/2013 Edition « whatsjohnreading

  45. Pingback: More Fictional Drugs Banned By The FDA | Slate Star Codex

  46. MugaSofer says:

    *feels urge to do something about this*

    Any chance you’ll ever share these advanced social skills you learned during your Five Thousand Years?

    Obviously, some of these techniques may be evil. But you have unparalleled access to the rationalist community, so I’m guessing the instrumental value could be high.

    Oh, and I’m crazy curious, of course. Hmm, I think I’ll ask this on a few posts in the hope it’ll be seen.

    Report comment

  47. Josh says:

    I purchased the 23andMe kit the day after the FDA nixed them. Therefore, I was unable to get health results from 23andMe. But I was curious as to how I could use the genetic data provided by 23andMe – they allow you to download your raw data.

    After some Googling, I found the 23andYou site. It contains a number of services that will tell you interesting information. Two of the services – one free, one $5 – will give you health data. The free site (run by a team at Stanford) will only cross-reference your genome with the SNP literature database and provide a list of scientific papers that correspond with SNP’s in your genome, then provide a very cryptic (for the layman) statistics chart. The second service costs $5 but it seems to provide information that is very similar to 23andMe’s health data.

    http://snpedia.com/index.php/Promethease ($5 service)
    http://esquilax.stanford.edu/ (Free service)
    http://www.23andyou.com/3rdparty (A list of other services)

    Report comment

  48. Victoria says:

    Victoria is my name, I am 39 years of age , from Henderson, NV, I have not done this before, but i think is will be of great benefit for me to come online and make my friends out there know about my encounter with a spell caster whom i met on net. I have had bad experiences over the years and this has made me bitter and skeptical about finding solution to my problem. Until my Aunt introduced me to a man who help her in the past and she was successful. I also did contact this man and to my greatest surprise i was so shocked for the wonderful works experience from him, He is so true to his word and what he says is what he does. I really appreciate you Lord Zilialia for you help. Thank you so much and i sincerely can’t thank you enough. you have indeed done what other spell casters i have contacted cannot do for me either they cause me pain and agony. Friends please make no mistake anymore here is a man who has been tried, tested and trusted and he never failed for once. contact Lord Zilialia on spellcaster1202@gmail.com today and put an end to your pain. don’t get deceived and scammed Lord Zilialia is true and genuine. I will forever be grateful to him till eternity. Lord Zilialia you are simply the best. Contact him spellcaster1202@gmail.com.

    Report comment

  49. Pingback: What Else Can I Do With My 23andMe or AncestryDNA Data? - Joshua Townsend

  50. Latesha says:

    When I initially commented I clicked the “Notify me when new comments are added” checkbox and now each time a comment is added I get three e-mails with the
    same comment. Is there any way you can remove people from that service?
    Bless you!

    Report comment

    • Andy says:

      I know, the comment subscription is annoying as heck.
      At the bottom of the emails should be a bit saying :
      “Want less email? Unsubscribe or modify your Subscription Options.”

      Report comment

  51. Stella John says:

    I have to keep you updated because I’m simply AMAZED at the results of this spell you performed for me. Everything is going so well and EXACTLY how you said it would be. Even though it took 5 months to fully progress, it was so worth it because things are just about at perfection! How you took my situation and completely turned it around to give me exactly what I wanted is beyond me, but something I will never question and just be completely grateful for coming across you. Bless you for helping so many people get what their heart desires. You truly gifted! . you can also contact him for help as well (arigbospelltemple@gmail. com)

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