Genetic Future

Steve Murphy is up in arms about a recent email from 23andMe to its customers advertising the use of genetic variants on its V2 chip to predict individual risk of statin-induced myopathy and breast cancer.

Of course, Steve does have a strong financial interest in 23andMe staying as far away as possible from the area of clinical diagnostics, but I share his unease here.

So far personal genomics companies have by and large done their best to steer clear of being seen as “doing medicine”, but this move would seem to put 23andMe explicitly over that line. In the case of the breast cancer variants this was very much an active decision. These are not markers that just happen to be present on 23andMe’s SNP chip; they were deliberately added during the design of the V2 product, along with risk variants for several other moderate to severe diseases (e.g. Bloom’s syndrome and Glycogen Storage Disease type 1a).

Intriguingly, both of these latter diseases and the three tested breast cancer variants are all much more common in Ashkenazi Jews than in the general population – suggesting that 23andMe may well have a particular target audience in mind.

In a post a month ago I explained why testing for “high-penetrance” disease variants (variants with near-deterministic association with disease, as opposed to the probabilistic increases in risk for the common variants 23andMe currently tests) might be a bad move for 23andMe in particular:

It’s unclear whether 23andMe intends to move more heavily into carrier
testing by expanding its range of conditions and associated variants to
lower and lower frequencies. However, it seems to me there are good
reasons to avoid such a move: doing so would seriously undermine the
company’s ability to characterise its service as non-clinical in
nature, substantially increase the risk of litigation for false
results, and potentially catalyse unpleasant regulatory consequences
both for the company and for the field as a whole. In addition, it’s
unclear to me whether extensive carrier screening would sit well with
the overall image of the company – there’s just not much that’s fun about the possibility of discovering potential child-killing horrors lurking in your genome.
Large-scale carrier testing is a product that would no doubt appeal to
many prospective parents, but it would feel pretty jarring sitting next
to cartoon movies about human evolution in 23andMe’s repertoire.

23andMe has carefully and skilfully carved a niche out for itself in recreational genomics, an area where a considerable market exists – as an illustration, Blaine Bettinger has recently noted that one company alone has sold over half a million kits for testing genetic ancestry. With the huge number of markers generated by their genome scan products, consumer genomics providers like 23andMe have the capacity to predict genetic ancestry better than anyone else in the market – and other features, such as the ability to trace the inheritance of simple traits through a family tree, are also highly attractive to the public.

23andMe has both the PR clout and the expertise in complex data visualisation required to completely dominate this substantial market; I’m not sure why it would risk all that by making an overt (and IMO premature) move into the clinical arena.

Of course, 23andMe knows a hell of a lot more about the incipient regulatory landscape of consumer genomics than I do – perhaps this move is not as risky as it seems?

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Comments

  1. #1 hibob
    February 15, 2009

    Myriad Genetics has stepped on everyone in the US and Europe that has tried to offer BRCA1/BRCA2 testing without a license from Myriad … Oncormed and Affymetrix tried it 10 years ago and got spanked, and so have hospitals and other companies since then. Did 23andMe move its operations to someplace that doesn’t concern itself about IP law?

  2. #2 Russell
    February 15, 2009

    Steve Murphy is fighting a losing battle. Yeah, there is some overlap between medicine and reading of a person’s genome, just as there is some overlap between medicine and teaching someone how to take their own pulse rate. But people want to know about themselves, and one of the reasons they want to know about themselves is precisely because of its influence on how they manage their health.

    I’m sure if companies like 23andMe are driven from the states, that there will be places like Antigua that welcome them.

  3. #3 Anonmyous
    February 15, 2009

    hibob: Word on the street is that Yale New-Haven performs some of their own BRCA genetic tests.

  4. #4 Kevin
    February 15, 2009

    If it isn’t 23andMe, it will be another company moving into this area. Biotech is moving at an ever accelerating rate while litigation and regulation remained firmly rooted in customs and traditions from the pre-industrial age.

  5. #5 Andrew Yates
    February 15, 2009

    Well, the more popular 23andMe, the more Steve get quoted as a counter-opinion at conferences and in the press. Second, the bigger the market for genomic tests, the bigger the market for physician consults who understand and apply genomic tests. It’s sometimes easy to forget this outside of our specialty web bubble, but the reaction of most physicians to “genomics” is “what?” Steve is a rare exception.

    (And I need to disclose my interest here by stating that I’m an employee of Helix Health) but I would recommend 23andMe tests for patients given clinical utility if the 23andMe terms of service didn’t make that impossible. Would you allow physicians in your practice prescribe a test with a label stating “do not act on the results of the test?” Talk about a risk management scenario…

  6. #6 Daniel MacArthur
    February 15, 2009

    Following up on hibob’s comment – I’m also pretty intrigued by the apparent disregard for Myriad’s patent. Does anyone know how 23andMe is getting around the licensing issues?

    Andrew – all good points.

  7. #7 Carl S.
    February 15, 2009

    If anyone here is a 23andme subscriber, they could also check their complete dataset and see if the V2 chip includes SNPs for Gaucher’s disease, Tay-Sachs, Canavan’s Disease, and all the other Ashkenazi conditions.

  8. #8 Carl S.
    February 15, 2009

    23andme may try to become a more informative Dor Yeshorim, which tests couples for the whole Ashkenazi panoply, but doesn’t inform the testees unless both are carriers.

    http://en.wikipedia.org/wiki/Dor_Yeshorim

  9. #9 Anon
    February 15, 2009

    I welcome this announcement.

    I think doctors have their role as gatekeepers for PROCEDURES (eg: surgery) and for dangerous MEDICINES (eg: opiates). But I don’t think that doctors should ever be able to prevent us from getting test results about ourselves.

    Anyways, why are the BRCA or statin tests necessarily “clinical tests”? 23andme’s position is basically: “These are NOVELTY tests for the curious. You CANNOT act medically based on them. If you have health concerns, talk to your doctor and get yourself RE-tested by a real medical lab.” Seems like a perfectly legitimate position in my view.

  10. #10 Steven Murphy MD
    February 15, 2009

    “These are NOVELTY tests for the curious. You CANNOT act medically based on them. If you have health concerns, talk to your doctor and get yourself RE-tested by a real medical lab.” Seems like a perfectly legitimate position in my view.”

    Why the HELL WOULD YOU EVER RETEST DNA? You are foolish to even suggest such a waste of insurers or patients’ money.

    As for the “legitimate position in your view”

    That is just plain gobble dee Gook and business double speak for performing a medically actionable test without taking responsibility.

    Since when was it ok to give up responsibility for one’s actions……oh, I forgot Bernie Madoff still is not in jail.

    As for my financial interests….I don’t own a clinical diagnostics lab…..I never would, it takes too much medico-legal liability. Even more than merely practicing medicine. Which is why I understand the forked tongue words of these companies…..

    If Myriad doesn’t stop 23andMe in this space, CDPH will. Either way, 23andMe has now moved into the clinical realm. Lab directors beware, they ARE coming after YOU…..Not me.

    So stop saying I have a financial interest, when the only interest I have is in the protection of my patients’ health information. Face it, Genomes ARE health information (as well as other informatics pieces)…

    Interesting move by Sergey, who is of Ashkenazi Jewish ancestry BTW…..

    -Steve
    http://www.thegenesherpa.blogspot.com

  11. #11 Steven Murphy MD
    February 15, 2009

    @ Anon
    “I welcome this announcement.
    I think doctors have their role as gatekeepers for PROCEDURES (eg: surgery) and for dangerous MEDICINES (eg: opiates). But I don’t think that doctors should ever be able to prevent us from getting test results about ourselves.”

    Anon,
    I always give my patients copies of the tests that I order. I also give them a walkthrough of each and every result……if not in person then at least on the phone….Because they deserve clinical interpretation.

    So who then should be the gate keeper to clinical interpretation? Non-Clinicians? Untrained Laypeople? Web designers? Infovores who are armed with a steadmann’s medical dictionary? If you have all the time in the world feel free to learn. But may I suggest, pony up the 180k USD, 4 years of study and go to medical school. In addition may I add another 3-7 years of residency training…..

    Be serious, do you think a few wiki searches can get you there that much quicker?

    I hope you don’t do your own legal defense…….

    -Steve
    http://www.thegenesherpa.blogspot.com

  12. #12 N/A
    February 15, 2009

    I predicted that 23andMe would turn clinical at the start of the new year. It was the only thing that made sense. (selling tests at Wal-Mart…others predicted, lol).

    All of this pull crap about non-doctors diagnosing diseases, giving medical information, and so much more is getting old. So many lay people think that understanding your own health is easy and only takes a few mouse clicks.

    N/A

  13. #13 Anon
    February 15, 2009

    @Steve: quote “Why the HELL WOULD YOU EVER RETEST DNA? You are foolish to even suggest such a waste of insurers or patients’ money.”

    Are you kidding me? There are all kinds of reasons why a test might screw up. A close friend of mine got a positive test for hepatitis at the local government run (!) hospital. They called her back a week later saying “Ooops, sorry, mix up in the lab. You’re OK.” It’s certainly *possible* that a genetic test offered at $400 wouldn’t have as many safeguards as a $4000 test. Things like double checking, air-tight precautions against contamination, etc. But they are ALLOWED to offer a cheap NOVELTY test that is not up to the standard of a MEDICAL test.

    When you compare 23andme to Madoff, you just sound shrill and irrational.

    When you suggest that only those who’ve paid $180k for medical training can interpret test results, you sound arrogant. Fact is, almost any motivated person can get more understanding about his condition from doing his own research than from a 10 minute meeting with his doctor. Unless of course you give unlimited question and answer sessions to your patients.

    Bottom line: I have an absolute RIGHT to access the information in my genome. I have a RIGHT to know what my genetic makeup is, and I DO NOT need to go through *you* for permission to access this information. Get over it!

  14. #14 Anonymous
    February 16, 2009

    Interesting move by Sergey, who is of Ashkenazi Jewish ancestry BTW…..

    -Steve

    What exactly do you mean by this, Steve?

  15. #15 Daniel MacArthur
    February 16, 2009

    So stop saying I have a financial interest, when the only interest I have is in the protection of my patients’ health information.

    Maybe I misunderstand your business model, Steve – are you running Helix Health as a charity?

    So who then should be the gate keeper to clinical interpretation? Non-Clinicians? Untrained Laypeople? Web designers? Infovores who are armed with a steadmann’s medical dictionary?

    Clearly, the argument is that there should be no gate-keeper, and that people should have the right to access and interpret their own genetic data however they choose. I’m a lot less sure of my position on this now than I was six months ago (when I was unambiguously in Anon’s camp) – talking to clinicians and ethicists in the meantime has shifted me slowly into more neutral territory.

    My major concern here is pragmatic rather than ethical: I simply don’t want to see 23andMe (in Andrew Yates’ memorable words) “call down the federal ban hammer”.

  16. #16 Peggy McKee
    February 16, 2009

    Of course, a company like 23andMe is going to go direct. This is financially the smart thing to do. And, of course, I want access to any test that I want to buy and can afford to buy (mind you not any test that I want the govt to buy for me). Because if someone else is paying, they get to say what they will pay for….Insurance plans, govt, etc. They get to regulate and stipulate what they will or won’t pay for. But the company can educate me as a consumer and encourage me to buy the test. If I get a result that I want some action taken on, then I will have to get a board certified physician to perform that action. Word of Warning To Consumers: Labs are ran by people. People sometimes make mistakes. Tests that aren’t FDA approved sometimes aren’t approved because of their clinical value, and sometimes it is because they are neither precise or accurate (meaning test many times = get many answers). So don’t jump off a bridge over 1 test, no matter who does it…
    I don’t think that the average consumer is ready to make their own diagnosis, but I do think that any education, excitement about DNA testing and what it might offer us in the future is a good thing.

  17. #17 Steven Murphy MD
    February 16, 2009

    Helix Health makes its profit from patients paying for medical consultations….Not by testing. I have explained this many times.

    Hepatitis testing is not Genetic testing…so that argument is bunk.

    If 23andMe goes clinical they should join the club and be regulated just like any other clinical test….No one else in healthcare avoids regulation, why are they special?

    If you say BRCA testing isn’t clinical, then I will consider you ignorant of the topic at hand.

    Answer that Daniel, please….Why should 23andMe escape regulation which governs all other clinical tests….even the DTC clinical tests?

    -Steve

  18. #18 Daniel MacArthur
    February 16, 2009

    Steve,

    Are you actually claiming that 23andMe moving into clinical genetics would have absolutely no financial consequences for Helix Health? It seems to me entirely plausible that customers who receive a detailed interpretation of a BRCA1 test from 23andMe would be less likely to feel the need for a lengthy chat with Dr Murphy. Whether that would be a sensible attitude is a separate discussion – but for the record, I think anyone who’s had a BRCA1 test would be crazy not to discuss it with a doctor.

    In a comment above, Drew Yates suggests that 23andMe’s move may actually increase the demand for medical genetic consultations. I’m open to that possibility too, and don’t claim to have a crystal ball telling me which of these two possibilities will win out. But either way, 23andMe’s activities in this domain are clearly financially relevant to you, Steve, and your attempts to claim otherwise are unconvincing.

    Some quick responses to the rest of your comment:

    1. Yes, I think BRCA gene testing is clinical; I stated explicitly in my post that in offering this test 23andMe appears to have “crossed the line” into medicine.

    2. I think if 23andMe offers BRCA testing, it should be subject to precisely the same regulations as any other body offering that test. The whole point of my post was that 23andMe’s apparent skirting of the regulation of clinical tests seems like a dangerous move, potentially threatening the entire industry. I don’t necessarily agree with the regulations (in fact I’m too ignorant to have much of an opinion either way), but I certainly don’t see 23andMe as having a free ticket out of Regulation Town.

  19. #19 N/A
    February 16, 2009

    How soon until 23andMe tests for HD? According to Annon’s theroy, a person can order a HD test (in the near future) and have a result that shows a mutation that will lead the tester to getting HD. Since the 23andMe test results can’t be used medically, the person once again has to take the HD test and once again deal with the results. Oh the horror of conflicting tests results. Do do I have an increased risk of getting HD or not?

    NO person should undergo a genetic test (I don’t give a crap about testing for the basic traits) without FIRST having a medical family history done.

    Why can’t people understand that it takes a good two decades or more to really know if a genetic test has any benefit with clinical outcome? Instead, these DTCs see a study publish from a GWS study that shows a gene mutation for this condition and they market the test to the general public.

    People, we need to know how common gene mutations that have been linked to disease onset is ALSO present in the general publication (with also looking into ethnicity).

    Genetic testing IS NOT something that should just be sprung up out of the blue by some person with only a B.S. degree of education. Sorry, that is how I see it.

  20. #20 N/A
    February 16, 2009

    “People, we need to know how common gene mutations that have been linked to disease onset is ALSO present in the general publication (with also looking into ethnicity).”

    Silly typo:

    People, we need to know how common gene mutations that have been linked to disease onset is ALSO present in the gneral population (with also looking into ethnicity).

  21. #21 Anon
    February 16, 2009

    >Hepatitis testing is not Genetic testing…so that argument is bunk.

    So you’re claiming that a genetic test can never be wrong? If you really think that, I’m sorry to say that your “US$180k education” is worthless. I’ve already given two examples above that could cause mistakes. Here are others: manufacturing defects in the gene chip, database lookup errors in the software code, hackers, etc.

    If you’re about to make a major health decision based only on a lab test, get a confirmation first by being tested again. This should be obvious, from a logical and malpractice point of view.

    I don’t think that DTC companies should be subject to heavy regulation because they clearly offer a novelty product. There is obviously a large market for that. But if you want to offer court room evidence of paternity or make medical decisions, you should get the regulated (and therefore more expensive) tests.

    Saying “only the regulated services should exist” is tantamount to saying “everyone should drive a Mercedes and Kia should be banned because it’s not as safe in a crash”.

  22. #22 Anon
    February 16, 2009

    Oh the horror of conflicting tests results.

    Easy: DTCs say their tests are not medically actionable, so rely on your doctor’s test. And ask for a refund from the DTC company since some of their info would have been in error.

    NO person should undergo a genetic test without FIRST having a medical family history done.

    Ridiculous. who are you to tell me what I’m allowed to know about my own genes?

    This kind of attitude really gets me steamed. Mind your own business!

  23. #23 N/A
    February 16, 2009

    Anon is showing lack of education. A family history can show what tests could be of value, which tests are not reallly needed (feel free to spend that one month of mortgage payment on that genetic test), and so much more. Requering a person to have a family history done is simple and fast (if the person knows what the heck they are doing). All DTC companies show require this before a person can order a test. BUT (and I MEAN BUT), doing so is practicing medicine. However, what 23andMe already does is is practicing medicine.

    Get a refund? LOL. Do they even have that in their terms of service?

    Let me guess, you are in full support of nutrigenomics at its very young stage? (and I’m refering to consumers orderinga a test, not the academic research behind it)

  24. #24 N/A
    February 16, 2009

    Hepatitis testing:

    Hepatitis A

    Also known as: HAV-Ab/IgM, HAV-Ab/total
    Related tests: Hepatitis B, Hepatitis C email this page

    print this article
    was this page helpful

    The Test
    ——————————————————————————–

    How is it used?
    When is it ordered?
    What does the test result mean?
    Is there anything else I should know?

    How is it used?
    There are two versions of the test, and these detect antibodies. Antibodies are produced by the body to protect itself from antigens (foreign proteins). IgM (immunoglobulin M) is the first antibody produced by the body when it is exposed to a virus and is used for early detection of infection. IgM antibodies to HAV are used in a patient with evidence of acute hepatitis, such as jaundice, dark urine, pale colored stools, fever, and loss of appetite. IgG (immunoglobulin G) antibodies develop later and remain present for many years, protecting the person against further infection by the same virus. A total antibody test (which detects both IgM and IgG antibodies) detects both current and previous infection with HAV and also will be positive after receiving the hepatitis A vaccine.

    [Back to top]

    When is it ordered?
    Testing for the presence of IgM antibodies to hepatitis A is done if you have the symptoms and/or are likely to have been exposed to the virus. If you have being considered for the HAV vaccine, a total antibody test may be ordered before you are given the vaccine to see if you need it (if the antibodies are already present, the vaccine won’t help you). Once you have completed the two doses of the vaccine, the total HAV antibody test can also be used to see if you have responded to the vaccine.

    [Back to top]

    What does the test result mean?
    If the test result is positive (or reactive) and you have not gotten the HAV vaccine, you have had a hepatitis A infection – even if you were not aware of it. About 30% of adults over age 40 have antibodies to HAV. If you have been given the vaccine, a positive result means you are immune to HAV and cannot be infected by it.

    [Back to top]

    Is there anything else I should know?
    It is presumed that one infection with hepatitis A produces lasting immunity against further infections.

  25. #25 Anon
    February 16, 2009

    “N/A”, your presumptions are amusing. I’d love to have an “education face off” with you.

    Of course I understand the value of having a family history screening. But I reject the idea that I should be required to get one if I want a test. It’s my money, and my genome, and you have no say over my personal choices.

    What I know of nutrigenomics is that it’s essentially bullshit. If it is bullshit/lies, then their “services” are really fraudulent. Like astrology, naturopathy, most of chiropractics, etc. There are laws against fraud on the books.

    This is not the case for DTC companies’ products. 23andme’s test results are real, and their information is very clear as to what your results mean (eg: “AA means your risk goes from 1% to 1.3%”). Often, it is not very useful, but they’re honest about it and I’m allowed to waste my money on useless shit.

  26. #26 N/A
    February 16, 2009

    Nutrigenomics is not bullshit. Offering tests to a consumer, at this point, should not be done. Studies have shown that a diet of certain foods can affect gene transcription. Therefore, nutrigenomics IS imporant.

    23andMe tests are real? So they puplish a paper showing an association and then offer consumters a genetic test? If you don’t believe this, this has ALREADY happend. This genetic test has not been reviewed by ANYONE.

  27. #27 Anon
    February 17, 2009

    The American College of Medical Genetics and the US Preventive Services Task Force have both issued clear guidelines about who should be tested for BRCA mutations and how it should be done. It seems pretty clear that many of these guidelines will be ignored by 23andme. Before you start arguing about whether a person has the right to such information, it is perhaps important to assess whether the information is of any clinical value to the people who will be buying it, and whether this clinical value will suffer when guidelines, based on years of collected evidence will be incompletely followed.

    It also presumes that the risks are well understood. heck, the literature that 23andme is citing on its (BRCA testing web pages (use a demo account to view them)widely diverge on what risks mutation carriers can expect. The work they write about in their text (King et al, 2003) found breast cancer risks by age 70 of 74% among BRCA2 carriers and 69% among BRCA1 carriers, as well as a 46% chance of developing ovarian cancer by age 70. On the webpage, they also cite an important article by Struewing et al…which found breast cancer risks of 56% and ovarian cancer risks of 16-22% by the age of 70 in carriers. Which risk numbers are correct? I dont know, you dont know, 23andme doesn’t know, but will their customers know that?

  28. #28 N/A
    February 17, 2009

    Quote: “risks are well understood.” Thank god you pointed out the flaw in that statement. I didn’t want to blow a mountain of stem off my head, lol.

    I evaluate statistics in journal publications all of the time for my job. The n will almost always vary, study methods will almost always vary, selection criteria will almost always vary, interpretation of their own data can be biased, etc.

    What these doops at 23andMe (and the other DTC companies) don’t take into account is the medical history and family history (I think one of them does this though). To get a better risk value, it is important to know, if the person already has a positive test for a gene mutation for breast cancer, what is the size of the tumor, age, ethnicity background, environmental exposures, etc, etc, etc.

    I have always said that direct to consumer genetic testing are not going to give accurate risk factors no matter how good they try to make it seem (DNA Direct is as close as it can come).

    *********

    Consumer: Orders a genetic test from 23andMe

    23andMe: Dear……you testes positive for a gene mutation at SNP1233455 on Chromosome 23. According to Bob Law, et al (2001), you have a 1.5% risk of developing ……..

    Thank you for ordering our test.

    Consumer: What? What does this mean? How does it compare to the general population? How does it compare to others who have not developed the condition that had the same risk factor…and why did some people with the same risk factor develop the condition?

  29. #29 Anonymous
    February 17, 2009

    OMG I’m practicing medicine by posting this family history health tool. Regulate me!

    https://familyhistory.hhs.gov/fhh-web/home.action

    On nutrigenomics being bulls**t:
    http://www.gao.gov/products/GAO-06-977T

  30. #30 N/A
    February 17, 2009

    The family history link that you posted is to be used by people to take to their doctor.

  31. #31 Ernie Bornheimer
    March 10, 2009

    Steve Murphy said:
    I hope you don’t do your own legal defense…….

    That’s a very misleading analogy.

    Here’s a better one:

    Having a doctor as the gatekeeper of my genetic information is not like hiring a lawyer to defend me in a trial. It’s more like hiring a lawyer who won’t let me see the evidence against me.

    Put another way, I should have the right to defend myself in a trial (however stupid that might be). Just as I should have the right to any of my genetic information, and decide to consult a doctor about it (or not, however stupid that might be).

  32. #32 BRCA mutation carrier
    March 16, 2009

    I find this new development terrifying. While I certainly agree that your genetic information belongs to you, offering these services without medical insight (especially not through a genetic counselor) is irresponsible at least and criminal at worst. When you learn that you have an up to 80% risk of early cancer, you need medical professionals to help you understand that risk in the context of your own particular family history as well as help you learn about your options for surveillance or prophylactic action. The average person may not be aware of the numerous academic centers that specialize in this area, nor the fact that the consequences of this information in a health record have become innocuous, and that insurance and medical professionals are supportive of learning how to manage one’s risk.

    Regardless of the ethical considerations of these tests (does a parent have the right to the child’s information for a disease that has onset as an adult, for example), it disgusts me that something like this is part of a business model for a fast-moving genetic company. Too bad, 23andme, I thought there was hope for you.

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