paternalism

"Integrative medicine": The lure of the shaman healer

oracknows — Mon, 09 Mar 2015 05:00:51 +0000

"Integrative medicine": The lure of the shaman healer

Quite to my surprise, apparently I've become fairly well known as a critic of so-called "integrative medicine," that which used to be called "complementary and alternative medicine" (CAM) but whose name was changed because its practitioners didn't want to be "complementary" to anything. Rather they wanted their woo to be co-equal with science-based medicine (SBM). Before that, what is now "integrative medicine" after having been CAM was known as "alternative medicine." (The wag in me can't resist further pointing out that before that it was mostly known as quackery.) As I like to say, the only thing “integrative” medicine adds to SBM is pseudoscience. I do my several blog posts per week, most here, at least one a week at my not-so-super-secret other blog, and people actually read the brain droppings I want to throw out into the ether. After over a decade, I still have to pinch myself, but even with my tendency towards extreme (for the Internet) logorrhea, I still have a readership.

One of the questions that keeps recurring over the years is: Why? Why are patients drawn to unscientific medicine. Make no mistake, the whole point of "integrative medicine" is to integrate medicine that has not yet been validated by science (or has even been disproven by science) with real, science-based medicine, although advocates of "integrative medicine" are very good at convincing themselves that they are just as science-based in their practice as any of us. Not surprisingly, they become very unhappy with me when I argue otherwise.

A couple of weeks ago, Scott Gavura mentioned how quackademic medicine has ppretty much completely overrun his alma mater, the University of Toronto. He was not alone. Joe "Dr. Joe" Schwarcz, a professor of chemistry at McGill University and director of McGill's Office for Science & Society, which is dedicated to demystifying science for the public, was also harshly critical of the dean of the Leslie Dan Faculty of Pharmacy at the University of Toronto for running a clinical trial of homeopathy for attention deficit hyperactivity disorder (ADHD), criticism that led to Heather Boon, the dean and PI of the study, to fire back. I don't want to discuss exactly what happened here, given that Dr. Joe's article, a post by Dr. Gavura, and another post by a certain "friend" of the blog all discuss those issues in detail.

Rather, I want to use a post by Dr. Mario Elia as a jumping off point. The post, entitled The lure of “integrative medicine”, begins thusly:

It has been fascinatingly frustrating over the past couple of weeks to see faculty and students at the University of Toronto defending “alternative” and “integrative” and “holistic” medicine with all of their might. They are portraying this entire issue as an “us vs. them” debate, as if anyone opposed to the idea of integrative medicine is also blind to new ideas, opposed to non-prescription treatments, and has no interest in patient satisfaction. Nope, we actually care about all of those things. And we care about the patient’s pocketbook and about the scientific method.

This is another example of the false dichotomy of CAM (or integrative medicine, or whatever you want to call it) that I've lamented so often, albeit in different terms. Usually, I point out that being a "holistic" physician does not require the embrace of pseudoscience. After all, that is a key implication often made by proponents of integrative medicine, namely that you have to embrace pseudoscience like acupuncture, homeopathy, naturopathy, and the like in order to be a truly "holistic" physician and take care of the "whole" patient. Obviously, they don't put it in those terms, but that's the bottom line in many of their contentions about the usefulness of integrative medicine. Opponents of integrative medicine are often painted as believing in "scientism," of not caring about the whole patient, and the like. As Dr. Elia points out, we're also frequently painted, either by implication or by assertion, as not caring about non-pharmacological treatments of various conditions and of not caring about anything that science doesn't understand very well.

Now here's where Dr. Elia nails it. He describes a patient encounter with one of his patients who has hypothyroidism. This patient also regularly saw a naturopath, who offered her a boatload of the usual things that naturopaths offer, such as supplements and herbal medicines. (As an aside, I'd like to mention here how I frequently laugh at how practitioners of SBM are accused of "pill pushing" and of only wanting to give patients a prescription for a medication that will help them when so often naturopaths and other alternative practitioners want to push supplements and herbs as the cure for what ails their patients. The difference, of course, is that as a physician I can't sell the pharmaceutical drugs that I presribe to my patients. Naturopaths and alternative practitioners can sell their patients the very supplements that they prescribe. But I digress.) In any case, after Dr. Elia found out what supplements his patient was on and trying to explain to her as gently as he could that there was no evidence that any of these supplements did anything for her hypothyroidism, this is what happened next:

I paused and asked her “What exactly about how you feel do you wish were different?”. She said she wanted to have more energy and be less stressed and angry. I asked how she feels when she leaves the naturopath. Fantastic, she said. After a fascinating discussion with her and her husband, I learned that my patient is quite religious, and has been frustrated for the past decade that she hasn’t found anyone locally who shares her sense of spirituality. Until she met this naturopath, as they have very in-depth discussions about her faith. I explained to her that the benefit she is seeing from the naturopath is from a sense of camaraderie, and not any diets or supplements or treatments she is offering. I told her that she can feel free to continue seeing the naturopath, as long as she realizes she is essentially paying for companionship. The pricey supplements and herbs are just along for the ride, and are unproven in terms of safety and efficacy. An expensive placebo while the companionship provides all of the benefit.

As I said, I think Dr. Elia nailed it here. Remember all those studies over the years that I've discussed about, for instance, acupuncture, in which the provider-patient interaction was as important—or more so—than any nonspecific effects of the acupuncture (e.g., this one)? This is the distillation of what "integrative medicine" really is, for the most part.

But what's in it for the integrative practitioner? I suspect it's reclaiming something that has been lost over the last couple of decades, the physician-patient interaction. As the financial pressures of practicing medicine have grown and patient face time has declined, it's understandable that some physicians would like to reclaim "the way it was," whether it ever really was that way or not. There exists in the collective consciousness a concept of the physician along the lines of Dr. Marcus Welby and Dr. James Kildare, kindly, benign figures whose influence and good intent were unquestioned by patients. Doctors also long for a perceived time when the will of the physician was generally unquestioned, and patients did what they were told.

I've frequently referred to this apparent view of the role of the physician in the physician-patient interaction by proponents of "integrative medicine" as that of the shaman. Indeed, no authority less than "America's doctor" himself (or, as I like to call him, "America's quack"), Dr. Mehmet Oz, has said just this, as I pointed out two years ago, citing an article about him by Michael Specter:

“I would take us all back a thousand years, when our ancestors lived in small villages and there was always a healer in that village—and his job wasn’t to give you heart surgery or medication but to help find a safe place for conversation.”

Oz went on, “Western medicine has a firm belief that studying human beings is like studying bacteria in petri dishes. Doctors do not want questions from their patients; it’s easier to tell them what to do than to listen to what they say. But people are on a serpentine path through life, and that is the way it is supposed to be. All I am trying to do is put a couple of road signs out there. I sit on that set every day, and that is what I am focussing on. The road signs.”

It's that role, that some doctors crave (and understandably so), that of the healer. Unfortunately, to attain such a role, all too many of them have embraced pseudoscience to the point of advocating "integrating" it into medicine. As I've pointed out before, throughout most of human history, that was the role of the physician/healer. It took many hundreds of years, which stretched into thousands of years, before it was fully accepted that medicine should be based on science. Arguably, it wasn’t until just over a century ago, with the advent of the Flexner Report, that medicine, in the U.S. at least, was placed on a firmly scientific basis. Indeed, what we now know as randomized controlled clinical trials did not see their debut, much less become the basis of determining which treatments worked and which did not, until the 1940s. Although physicians have been trying to base their craft on science for hundreds of years, it’s really only been in the last century or so that they’ve succeeded.

Yet still some would like to go back to the way it was. They yearn for the days when doctors were “healers” and shamans, the way medicine was for hundreds and hundreds of years before science intruded. Indeed, I've lost track of how many times I've taken notice of rhetoric from practitioners of "integrative" medicine that basically says just this, usually with the implication that to attain that hallowed role of healer requires the embrace of various pseudoscientific—or perhaps I should say prescientific—treatments. And it works, too! Dr. Elia illustrates this with a question:

Can you imagine if physicians used the same predatory techniques that these alternative practitioners do? A patient comes in with viral pharyngitis, and I tell them it will resolve on its own, not to worry. It resolves on its own within 48 hours. Or….I could offer them some special herbal concoction, and voila! The herbs cured the sore throat in just 48 hours! Amazing! Dr. Elia is the hero! Patients need to realize the humility that physicians show in allowing the concept of tincture of time to run its course without creating a false sense of a cure through bogus practices. I am bound by evidence and science, not by pricey cures and by the ego-boosting of “curing” illnesses. The public would truly be amazed at the proportion of my day spent simply ruling out serious disease and providing reassurance, allowing time to take its course. Not as sexy as being a hero, but it’s the only ethical way to practice.

Indeed.

Of course, that's the problem with "integrative" medicine. Basically, it is based on using interventions that either haven't been shown to work or have been shown not to work and then taking credit for what would happen anyway even if the practitioner did nothing. Now, don't get me wrong. Practitioners of SBM are sometimes guilty of this as well, but SBM isn't built on the very model of placebo effects and regression to the mean. Integrative medicine is. SBM is all about producing real therapeutic effects. Integrative medicine doesn't much care if there's a specific effect. After all, any specialty that embraces naturopathy, traditional Chinese medicine, homeopathy, and even "energy healing" can't be too concerned with verifiable science, its protestations otherwise notwithstanding. As I've said before many times, the "central dogma" of alternative medicine/CAM/integrative medicine is that wishing makes it so.

It's not for nothing that I (as well as Kimball Atwood) have referred to CAM as the "new paternalism." It's not SBM that's paternalistic.

Dr. Elia "gets it":

“Integrative health practitioners” often point to patient satisfaction as a rationale for their existence and for funding, which is completely insufficient as a measuring stick for appropriateness in health care. We know that simply having an individual listen to your concerns and show empathy will improve outcomes, regardless of the form it takes. So take Reiki, and craniosacral, and therapeutic touch, and any mind-body energy life-force practices, and call them what they truly are. Relaxing companionship. Then let’s have a discussion about whether public funds should be directed towards that end. And let’s tell private-paying patients that they are paying for companionship and relaxation. But don’t try and explain these techniques via unproven scientific principles as a means to give them legitimacy. Perhaps many of these practitioners can work to develop self-directed education programs for patients to help those improve their own stress. Less lucrative, but far more patient-centred.

I'm not going to hold my breath waiting for this to happen.

oracknows Mon, 03/09/2015 - 01:00

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"I would like to take us all back a thousand years..."
---- Dr. Mehmet Oz

Indeed.

One might think that selling supplements and hand holding are somewhat easier paths of study and income generation than, you know, science.

In my younger days, physicians were expected to have a good "bedside manner", or so the talk went. They were at most half joking. But financial pressures have pushed physicians away from that model, and I think you and Dr. Elia are correct to see that "integrative" practitioners are trying to exploit this gap. People often want a sympathetic ear, and sometimes they will pay good money for it (ISTM that many therapists work on this business model). But that leaves them vulnerable to charlatans. It's a variation on "The Emperor's New Clothes".

I don't want to be taken back a thousand years and I doubt anyone would really want that. At least if they realised what living a thousand years ago really ment.

it's a vicious cycle which seems to "work" for both parties.
The patient gets the sense that someone is listening to them and allowing them to "control" their health and heal themselves by paying for supplements, meditating or whatever.
The CAM practitioner gets paid for essentially nodding reassuringly and selling them useless stuff.
Unfortunately they create an echo chamber around themselves via friends and social media which validates all of this and drowns out anything they don't want to hear.
Many SBMs would agree that a good bedside manner, companionship etc. are all potentially important to a patient's (primarily mental?) wellbeing but given the economic pressure they are under if something has to give then this is the first casualty.

"Doctors do not want questions from their patients..."

Bull f#cking sh!t Mehmet you arrogant twit. In my experience you can have a good partner in health if you approach a physician with an inquisitive humility, the very opposite attitude of what CAM tries to instill in their clients: every alternative practitioner I saw pissed away privately on idea that doctors don't know very much, that they are mostly incompetent boobs except in the ER. The distrusting insistent ignoramus-savant CAM would have you become would try even Marcus Welby's patience.

The CAM-patient relationship is about a secret knowledge shared with you because you are so special to have come to CAM. Saccharine lather applied to egg you on and keep you coming back for more. Doctor Oz soils himself on national television and you smile knowing you are lucky to be a part of this.

Indeed. The way many alt-medics and friends talk, I often wonder: Have you been to a doctor lately? They don't always have the time we'd like but nor are they trying to sign you up for weekly crystal hugging sessions either. Generally, I find that they try to address the problem as quickly as possible, via the least onerous means whilst accounting for patient needs and preferences. In an ideal world, they'd have nice rooms and herbal tea and decent food in hospitals which would achieve most of the 'benefits' of CAM without the fairytales plus bonus science. Now that's real 'integrative' medicine.

Another aspect to CAM therapies I've noticed could be termed: things that do work but are not particularly exciting or able to be trademarked without accessories or a hefty dose of pointless ritual. E.g. eating vegetables, regular exercise.

Excuse me now while I take my ancient African seed-based tonic to stimulate mental clarity and increase energy.

@DevoutCatalyst.

OK I feel like I need to find out where Dr. Oz did his residency and avoid anyone from that program if they were trained to never listen to patients, ever. YIKES!

The only questions from patients that I've heard docs don't like is the so-called door knob questions. You've gone over everything, did the tests, did any teach-back needed (where the patient tells you in their own words what the problem or treatment is) wrote the prescriptions, made the referrals and you put you hand on the door knob and the patient says something like oh doc, just one more thing...and it usually is some kind of alarming symptom that would have changed everything in the above list had you only known about this at the beginning of the appointment.

It is one of those human quirks where if we are really scared about something, or embarrassed we tend to put off bringing it up and then all of a sudden the appointment is over, especially if you've been fretting about it and wondering how to bring it up and may not even have really heard the important info about the other thing.

I just noticed, that we don't see much striving for integration in other branches of science.

I'd love to have resources required to invite the most vocal integrative medicine to a flight in plane organized in the spirit of integrative aeronautics.

In the middle of the flight the pilot would be replaced with shaman in trance connection to the Great Condor who'd steer them to safety through his holistic and natural understanding of how birds fly. And tank would only be filled to half capacity, since after the initial part of journey incense and focused will of passengers will suffice to take control of the journey, to creathe their path to flight. Well that and maybe some coffee enemas.

The news reports today that Cassandra C.'s cancer is in remission. http://tinyurl.com/nn7gyjt

There's no word from Cassandra herself, so mom Jackie Fortin is still running the show, and lawyers are apparently still trying to fight the State mandate. But Cassandra's doing the treatments, and the docs are reporting progress. Perhaps she'll be clear by the time she turns 18, should she decide to forgo further treatment at that time?

OK I feel like I need to find out where Dr. Oz did his residency and avoid anyone from that program if they were trained to never listen to patients, ever. YIKES!

Agreed. Although this is probably alt-med spin on what I imagine doctors were actually told, which is something more like "Never put patient comfort above patient health, should the two ever be at odds." Which, in an ideal world, they would never be. But patients are notorious for wanting to do what feels good, rather than what is good for their health. It is the job of the doctor to persuade/teach them otherwise.

@ The Smith of Lie:

I should ask my cousin, an architect, if there are any recent innovations in complementary or integrative architecture.

I can imagine that outdated concepts like the arch and cantilever might be replaced with more spiritually relevant formulae like praying that that wall will hold or wishing for a sufficiently strong foundation.

@Orac

I frequently laugh at how practitioners of SBM are accused of “pill pushing” [...] but I digress

It's actually a very good point worth repeating, because it's a prime example of the cognitive dissonance - or should I say, hypocrisy - of the alt-med practitioners.
Homeopathy is all about pill pushing, chiropracty is all about visiting every other week if not more often...
Not to mention the detox crowd which is all about cleansing oneself by pushing chemical stuff one way or another into one's body.

MNA: In an ideal world, they’d have nice rooms and herbal tea and decent food in hospitals which would achieve most of the ‘benefits’ of CAM without the fairytales plus bonus science. Now that’s real ‘integrative’ medicine.

Oddly, I've had an idea very much like it, but it's more to encourage vaccination. Parents who vaccinate, regardless of income level, get tea, snacks, toys for the kids and reading material that was published within the last year. Parents who don't get the room with one flickering lightbulb, no tea or toys and reading material that's older than their kids.

I am very lucky. My family doctor makes his patients feel very comfortable. From the moment he comes to the waiting room to greet me, shakes my hand and walks me back to his office I start to feel better. Oh, and when warranted he prescribes real medicine or finds a specialist for me.

In my experience the specialists are more likely to see me as an inconvenient vessel for a particular problem.

Smith @9: I take it you don't live in the US, because we have plenty of that happening here. Consider how difficult it is in the US to get high school biology classes to mention evolution. Or more recently, witness the Department of Environmental Protection in a US state that is particularly susceptible to seal level rise (because in many areas of the state, 5 m elevation is high ground, relatively speaking), being banned from using the terms "climate change" or "global warming". We have now had 360 consecutive months (30 years) of global average temperatures above the 20th century average--that's significant because 30 years is the standard minimum baseline for determining what climate is.

Denice mentioned architecture. There is something called "feng shui", alleged to be of Chinese origin (as you might guess from the name), which has significant effects there. But at least feng shui practitioners don't doubt the calculations of structural engineers regarding what is needed to ensure the building remains standing; they are more concerned with placement and aesthetics.

#12: Monty Python has something on belief-based architecture:

http://www.montypython.net/scripts/mystico.php

The skit itself is on YouTube, somewhere.

Um, I can't point and laugh at Florida as my state legislated the rate at which the sea may be allowed to rise.

Denice, we must of course remember the amazing Mystico and his assitant Janet, who put up blocks of flats by hypnosis. They work great as long as people believe in them. ;-)

https://www.youtube.com/watch?v=1ujRE2IkEIo

Mr Verybigliar: Well there is a considerable financial advantage in using the services of El Mystico. A block, like Mystico Point here, would normally cost in the region of one-and-a-half million pounds. This was put up for five pounds and thirty bob for Janet.

We have the relaxing companionship here in PDX:

Cuddling professional Samantha Hess of SE Portland fills the need for love -- nonsexually

http://www.oregonlive.com/portland/index.ssf/2013/11/professional_cuddl…

*bril*

Love this blog . . . thank you all for expressing so clearly and completely what I can not. I've tried to explain to friends and acquaintances that MMS won't cure cancer, that there isn't a secret cure for HIV infection, that a "colon cleanse" is really just sh**ting and apple cider vinegar can't perform miracles, etc. I'm usually accused of contempt prior to investigation, which is true, but is it just lazy to not "see for yourself" the benefits of a hydrogen peroxide enema? It totally amps up my PVCs to engage with these people, so I don't. Oh, did you know that beet juice will help cardiac dysrhythmia?

My light bulb went on in 1995 while was speaking on a panel that included Christine Maggiore. I had no idea who she was (I don't think she was yet the "somebody" she became). It turned out we'd had the same M.D. at some time -- my experience with him made me much more interested in SBM. Christine, obviously, not so much. At the time, I just thought she was making some unwise choices concerning her healthcare.

The healer/companion characterization hits it on the head. In addition to taking a lot of prescribed medication and participating in many clinical trials, I played with CAM because ***I liked the attention***. It always felt like the benefit, to me, was the feeling of being ministered to. I never had any belief in the CAM, itself. The needles, the stinky herbs and the annoying new age muzak were all just things to be endured while a kindly person made nice on me. Although I felt the treatments were bogus as f***, it was for the most part, sweet to be treated sweetly ---> and it was FREE. There really was that time for us (HIV infected) in the 80s to mid-90s when it felt there relatively little else to do. If nothing else, it was a diversion. It's gruesome that some were sucked over the event horizon, into total delusion.

Things have changed and CAMmers seem much more aggressive now. There's a pervasive "ortho" vibe EVERYWHERE that's like a magic carpet for this stuff to travel on. They are a pain in my ass, even though I really have nothing to do with them.

I'm very grateful to all of you who are able articulate (and back up) this stuff so well . And to the woophiliacs who frequently comment: please continue to toss those logs on the fire. It helps to keep the fire of reason burning bright.

Take us back just a few hundred years to get the cartoon on my fridge: "Yes, it's a golden age, or could have been, were not everyone swarming with lice." (add your own infectious disease.)
2nd thought: The idea that maybe we just need more therapist types might be worth investigating. Insurance pays for lots of that. It might be admitting you have a different problem than you wanted to have though.

We have the relaxing companionship here in PDX:

Cuddling professional Samantha Hess of SE Portland fills the need for love — nonsexually

Yeah, there are snuggling services popping up all over the place. I find the idea a bit weird myself, because
1. I'm definitely not comfortable inviting a stranger over to my apartment to cuddle with me, and
2. what's the other option, cuddle with a stranger in public?

Plus I have a gay faux boyfriend I can snuggle with.

2nd thought: The idea that maybe we just need more therapist types might be worth investigating. Insurance pays for lots of that. It might be admitting you have a different problem than you wanted to have though.

Yeah. I have some friends back in PDX who see SCAM artists for various chronic ailments. I have a feeling that the ailments have one name and that name is depression, but somehow saying that would come off as an insult.

I mean, I can sort of see why people want to have a physical illness instead of a mental illness - physical illnesses tend to garner a lot more sympathy and understanding. Nobody expects you to "snap out of" lupus.

Cuddling professional Samantha Hess of SE Portland fills the need for love — nonsexually

I see from the link she charges $60/hour. She must be really good at hugging. I've worked a helluva lot harder for a helluva lot less.

I learned that my patient is quite religious, and has been frustrated for the past decade that she hasn’t found anyone locally who shares her sense of spirituality. Until she met this naturopath, as they have very in-depth discussions about her faith. I explained to her that the benefit she is seeing from the naturopath is from a sense of camaraderie, and not any diets or supplements or treatments she is offering.

Yes, the patient was clearly interested in the camaraderie but I think there's more than an expressed desire for companionship in this confession. What about religion? The patient was having her spiritual views reinforced. She was essentially going to a religious leader who also provides evidence for 'miracles.'

My pro-alt med friends are very clear indeed that CAM is a matter of faith. It involves spiritual forces or metaphysics directly linked to Mind over Matter (ie wishful thinking in full blown New Thought armor.) All of their defenses -- and those of other proponents -- smack of the very same apologetic approaches and arguments atheists get from people who believe in God. And the very same indignant outrage over insensitivity and incivility. It's a choice which should never be "attacked."

A lot of people probably do like the friendly attention. But when health is specifically extended into mind, body, and soul, it looks to me like that the last one is what is uniquely being integrated into "integrative" medicine.

After over a decade, I still have to pinch myself, but even with my tendency towards extreme (for the Internet) logorrhea, I still have a readership.

Q: What's the distinction between logorrhea and being satisfyingly thorough?

A: A satisfied readership.

Denice, does feng shui qualify as complementary architecture?

For sixty bucks a whack I'd expect a lot more than a cuddle.

Speaking as someone with a thyroid problem and who takes synthetic thyroid hormone –

Taking supplements recommended by the naturopath could well be interfering with the thyroid medication that this patient is taking. Dr. Elio doesn’t say whether he explored this with the patient. It is known that calcium, magnesium, zinc, aluminum and iron supplements interfere with thyroid hormone absorption. I bet anything that the naturopath is recommending mineral supplements.

It sounds like the patient had some inkling that the supplements might be causing an issue, which was probably why she wanted the doctor’s opinion of them, and also why she continued to feel unwell. Instead of discussing these issues, however, she got a talk about companionship and placebos.

I’m not certain what the situation is like in Ontario where Dr. Elio practices, but if it’s like the US, he probably doesn’t have the time to sit down with a patient such as this and go over the details of what they are taking and how they need to manage her condition. Which just pushes this type of patient back into the arms of the naturopath, where her medicals needs are not being met, on top of wasting money.

Rork: "The idea that maybe we just need more therapist types might be worth investigating. Insurance pays for lots of that. It might be admitting you have a different problem than you wanted to have though."

Rork, I'm guessing you live somewhere other than the U.S. As far as I know, insurance in the US doesn't pay for therapy, and if it does, it's only for three months or so. And that's assuming the insurance company doesn't dump the person for having depression or some other thing.

And that’s assuming the insurance company doesn’t dump the person for having depression or some other thing.

No longer a thing (pre-existing conditions, that is) since the ACA took effect. Yay.

But yeah, mental health coverage is woefully inadequate on many plans. Mine has shockingly good mental health coverage, all things considered; I guess the university has some interest in not having grad students jumping out of windows or something. Although having windows that don't open, at least in my building, would seem to put the kaibosh on that anyway.

Rork, I’m guessing you live somewhere other than the U.S. As far as I know, insurance in the US doesn’t pay for therapy, and if it does, it’s only for three months or so. And that’s assuming the insurance company doesn’t dump the person for having depression or some other thing.

Well I guess we can add this to the ever-growing-list of things you don't know but try to speak authoritatively about.

@Renee #28, my doctor's office asks about all the medications I take, and make it very clear that they mean all of: things someone has prescribed, any OTC medications, any vitamins, and supplements. And every visit they give you a copy of the whole list for you to mark any changes on, it's all in their computer system and absolutely everything is cross-checked for interactions. One of the pluses of being in a medical group affiliated with a university in a tech-happy area, I guess?

O/T, but in case our esteemed host is looking for blogfodder, the Encyclopedia of American Loons had an interesting piece on Daniel Amen.

The Encyclopedia appears to be on its third pass through the alphabed -- there are always more where those came frome.

Eric Lund # 16
Well yes, I live quite far from States. Far enough that we only just started picking up on the trend to believe that vaccines cause autism about year or two ago and it still is relatively minor thing.

I admit I did not account for things like creationism or global warming manufacturoversies in my previous post. Still I stand by my point that one does not see the same push in areas where hard and fast science happens with binary outcomes. I doubt even the biggest enthusiast of feng shui would want his home blueprints to be created by a guy who has no formal knowledge of architecture.

I think it would just satisfy my vindicative streak if I could watch all the woo meisters forced to choose between their woo and science based solutions in a very quick and binary life or death situation.

@#28 Renee

My clinic here in the Midwest (hardly a hotbed of hi-tech) is the same as Emma describes. It was the same when I lived elsewhere (three other states). Every doc I’ve been to in the last 15 years (I move a lot) ask about all medications and specifically asks that you include any supplements or herbal stuff. This sheet is in your file (or on the computer these days). I also think that Dr. E from Ontario would have considered this aspect even if he didn’t specifically mention it.

JP: Although having windows that don’t open, at least in my building, would seem to put the kaibosh on that anyway.

Gotta love those 19th century buildings. I lived in a dorm like that one summer- I could probably have baked bread on my desk.

Science Mom: I have insurance, I just have never bothered to use it to attempt to get therapy or even medication(in fact, I haven't used it at all in a couple of years.) The insurance companies can and do rewrite the coverage constantly. And if anyone actually believes that the ACA will still be around in 2016- well, I have landmarks that are on sale.

Eric Lund @#3
Perhaps one way to think about CAM is that "bedside manner" has become a sub-specialty.

Gotta love those 19th century buildings. I lived in a dorm like that one summer- I could probably have baked bread on my desk.

It's actually 20th century - a truly hideous artifact of red-brick brutalism. The local myth about the non-opening windows is that, since the building was built in 1970 or thereabouts, it was made to be riot-proof and bullet-proof. (The campus was considerably more radical once upon a time.) I think a more likely explanation has something to do with heating, cooling, circulated air, etc.

The windows in my apartment building do open, but I am only on the second floor. Alas.

I have insurance, I just have never bothered to use it to attempt to get therapy or even medication(in fact, I haven’t used it at all in a couple of years.)

Hmm. I think I remember, a few months back, you mentioning going off an SSRI, although I may have you confused with somebody else. Was it unhelpful? Were you seeing a therapist at the time? The places I've gone to, you had to be seeing a therapist in order to see a psychiatrist. I did find that therapy had some value in helping to keep my head together, although I got pretty discouraged with it ultimately due to a failure to find a therapist I could "click" with in any significant way. I suspect this may be due to being too smart for my own good.

^ The "I have insurance" bit was supposed to be in a blockquote.

What is the number one used form of medicine on the planet?

JP: The SSRI was either in college or high school, back when I could be sure of coverage. I've been on two different ones, and found them both equally unhelpful. I wasn't seeing a therapist when I was on either. I think either my pediatrician or my other doctor (probably the other doc) prescribed them for me. Therapy never came up.

Science Mom: I have insurance, I just have never bothered to use it to attempt to get therapy or even medication(in fact, I haven’t used it at all in a couple of years.) The insurance companies can and do rewrite the coverage constantly. And if anyone actually believes that the ACA will still be around in 2016- well, I have landmarks that are on sale.

Don't shift the goalposts and try to obfuscate because you are called out for talking through your arse again. Take this advice or not but just stop making ignorant blanket statements based upon your own narrow worldview and scant life experience. You're really just embarrassing yourself.

@PGP:

Huh. Yeah, the whole phenomenon of GPs prescribing antidepressants is a little weird to me, and it seems extremely common.

Given that you do have insurance, if you think it might be helpful, you might look into seeing if they do offer coverage for therapy. A lot of plans do only offer a certain number of weeks, or only CBT, say. It can be helpful in general to have somebody to bounce one's cognitions and assumptions off of.

Of course, a good friend can be helpful in that regard, too.

Yeah, the whole phenomenon of GPs prescribing antidepressants is a little weird to me, and it seems extremely common.

Where I'm from, the standard procedure seems to be that they prescribe antidepressants, and if that doesn't work then they send you to a therapist. Given that pills are cheap and therapists are not, that may be a sensible way to spend healthcare funds efficiently.

Myself, I was on SSRIs for a few years; they weren't unhelpful - I wouldn't be sure I'd be around here to type without them - but neither did they bring me back to normal. The first therapist I got sent to didn't seem to make a difference, but when I got a new one things "clicked" and I improved fairly rapidly.

Given that you do have insurance, if you think it might be helpful, you might look into seeing if they do offer coverage for therapy.

We've been through this. There are different excuses, such as losing the insurance and vague surveillance concerns.

Sciencemom: Like anyone even understands health insurance.Can you tell me what your insurance coverage covers and what it does not, this year? How about next year?

JP: I think that's always been the case, at least in the US. Therapy might be helpful, but it can wait, until I have some gold-plated insurance plan. I can always talk to the cats and dogs I look after. Friends would be nice, but the one I could trust moved away.

Like anyone even understands health insurance.Can you tell me what your insurance coverage covers and what it does not, this year? How about next year?

I got a booklet not long ago with complete details on what my insurance does and does not cover, along with a notice that my copay had gone up again, to $25, which is still not bad. I'm guessing this is pretty typical, though if you don't have a current booklet, such information can be found online.

Therapy might be helpful, but it can wait, until I have some gold-plated insurance plan.

Can you check what your non-gold-plated insurance plan covers? It might be more than you think. And I wouldn't be too worried about losing coverage for using it. GradCare is admittedly pretty good insurance, but I've used it quite a bit, and so far, so good.

I can always talk to the cats and dogs I look after.

Dogs and cats are great, but they don't talk back, to my knowledge.

Friends would be nice, but the one I could trust moved away.

Do you have a phone? Or an email account?

Sciencemom: Like anyone even understands health insurance.

Speak for yourself. And speaking of which, if you don't understand the topic, then why are you making such blanket statements about it? Again I assure you that your myopic experiences do not even begin to scratch the surface of our complex world.

Can you tell me what your insurance coverage covers and what it does not, this year? How about next year?

I have exceptionally good insurance coverage so my experience is not generalisable (see how that's done?). But with the exception of minor changes in coverage, it has been very stable for years now. I don't profess to be an insurance intuit so I will refrain from guessing what will happen in the future.

It's one thing to integrate with a group's traditional healers when that group is fairly new to modern medicine (good politics) like the people in the photo seem to be. They've no reason to trust the stranger and his odd ways. And maybe, just maybe, you can teach the traditional healer some modern things, if the two of you can build up a good relationship. However, Europeans' traditional healers were by and large replaced with physicians centuries ago. Doctors are our traditional healers!

Our family has been poorly served by our physicians over the years, in many serious ways, resulting in much unnecessary suffering, some of which will never be overcome due to lasting neurological, other physiological, and psychological damage (lives derailed, many years of pain and illness, etc.). We are educated, proactive, intelligent, and have good (and very expensive) health care coverage. The maladies were easily discovered, obvious, and not rare. And further complications easily avoidable. In my opinion, the problem starts in medical school; there is an obvious deficit in diagnosis, including teaching how to piece together a puzzle, and a built-in skepticism of the patient. This speaks of an arrogance, and being taught to disrespect and disregard the observations of the patient or the parent (mother). It also speaks of constant haste and being overworked.

Physicians are also now between a rock and a hard place that started when the insurance companies became the middle man and took away their profits. Their incomes dropped, and along with that their political muscle, and their ability to self advocate as a group. They lost more and more income and the power to do anything about it. In order to support a practice they are forced to see many patients, quickly, and work long hours. Many cannot support their families on their incomes.

Then comes Obamacare, which has placed remaining profitable practices in the position of sharing their income with those that are unprofitable. This is socialism. I am the wife of a physician (a specialist), and his job has required both of us. We have worked very very hard all of our lives, and find that we are pretty much left stranded. We have our savings to rely on for retirement, but we need everything to raise our children. I try to explain to people that in order for a physician to be first rate, it takes two - his job is a two person job. I gave up my career for his. I recommend to physicians that they choose between their profession and having a family - it is practically untenable to attempt both.

Regarding the new quackery movement. I see friends go through all kinds of ridiculous exercises, and to no avail. Herbs and fake herbs are not the solution. I have been exploring the origins of a couple of herbs since learning of the recent testing of certain herbs in major chains, and most ingredients come from China, with a few exceptions. The supply chain is opaque, and there is no way to know the truth.
I am also concerned about the pharmaceutical industry and the cost of developing new drugs. Is the purpose of these mergers really just to enrich the top executive(s)?
Thanks for reading.

Why you CAN have your $1000 genome - so long as you learn what to do with it [Genetic Future]

sb admin — Fri, 07 Jan 2011 09:10:00 +0000

Why you CAN have your $1000 genome - so long as you learn what to do with it [Genetic Future]

As part of his Gene Week celebration over at Forbes, Matthew Herper has a provocative post titled "Why you can't have your $1000 genome". In this post I'll explain why, while Herper's pessimism is absolutely justified for genomes produced in a medical setting, I'm confident that I'll be obtaining my own near-$1000 genome in the not-too-distant future.

Matt's underlying argument is that while sequencing costs will continue to drop, obtaining a complete genome sequence that is sufficiently accurate for medical interpretation will require additional expenses (increased sequence coverage to ensure accuracy, all of the computation required to stitch the raw data into a useable form, and paying doctors to perform the interpretation) that will keep the cost of medical sequencing well above the arbimagical US$1,000 threshold. Instead, Herper argues, we will likely see medical-grade genomes stay above $10,000, or at least above the $2,000 currently forked out for MRI scans.

There's certainly some depressing truth here. I believe Herper is right that if you intend to access your genome sequence via a traditional medical route, it will certainly cost more than $1000 for the foreseeable future - if indeed you can get access to it at all, which is by no means guaranteed. The costs of clinical sequencing will include even more overheads than Herper notes in his short post: for instance, even as the accuracy of high-throughput sequencing technology improves, there will still be a need for variants with major medical impact to be independently validated in clinical labs, and custom assays don't come cheap.

However, many of these extra costs of clinical sequencing will be further inflated by regulatory demands (at least some of which will be arbitrary and pointless), and many will only apply if you obtain your genome through the medical system. Individuals with the motivation to seek alternative routes will be able to obtain a perfectly serviceable genome sequence at a substantially lower price: they'll have to be cautious in how they interpret the results, of course (although, importantly, this is also true of a medical test), but it will be possible to obtain substantial and potentially extremely useful information from your own genome without having to pass through the clinical toll-booths.

The key obstacle will be the development of cheap (or free), intuitive tools for annotating large-scale genetic information. Purchasing the sequencing itself will be trivial: even if the FDA succeeds in crushing innovation in direct-to-consumer genetic testing in the US, there will be plenty of companies abroad (especially in East Asia) willing to convert a mailed saliva sample into an assembled genome sequence. What the individual needs to do with that sequence is to (1) validate that the sequence they receive is in fact their own genome; (2) extract medically useful variants; (3) confirm that these variants are real; and (4) figure out how that information should be used to make health and lifestyle decisions.

Only one of these steps (the final one) will require direct consultation with the medical profession. The first will require comparing the sequence with independent genetic data (such as a genome scan from a company like 23andMe) to check that the two match the same individual (i.e. you), and also to provide an indicator of the global quality of the sequence. The second step is currently extremely challenging, but we can expect tremendous innovation in genome interpretation software and databases of functional variants over the next few years that will gradually simplify and improve this process. The third step will require sending another DNA sample to a company that does affordable, custom assays of a small number of genetic regions of interest using an independent technology. And the final step will involve discussing the results with everyone who might be able to tell you something useful about them, including your family and your doctor.

None of this is simple, but it will become easier with time. As the retail costs of sequencing drops, a substantial niche will develop for innovators providing affordable, intuitive, accurate interpretation tools (embryonic versions already exist: see, for instance, Promethease or Enlis Genomics). Open-source academic software built for large-scale sequencing projects will be adapted for use by non-specialists. The increasing availability of large-scale computing power (for instance, via Amazon EC2), coupled with this intuitive software, will make even compute-intensive analyses available to the educated, motivated lay-person. (Incidentally, tracking and fostering the development of these tools is one of the motivations behind the Genomes Unzipped project - and you'll hear more about our plans in this area in 2011).

Done carefully, there's no reason why a DIY genome couldn't be every bit as useful (or indeed as useless, in many cases) as one obtained through the doctor-as-gatekeeper route. As Dan Vorhaus argued after last year's sample mix-up at 23andMe, it is likely that clever DIY genomicists will be better at picking up certain kinds of errors (such as sample swaps) than clinical labs would. In terms of accuracy, while retail genomes may not reach the same quality standards as those generated by clinical labs, increased competition and innovation in the direct-to-consumer space will mean they're unlikely to lag too far behind - and judicious use of independent validation of important variants would in most cases raise the reliability to a level is equivalent to, or even higher than, a medical-grade test. Of course, for the very small number of genetic variants per genome that might require urgent, serious action - such as BRCA1 breast cancer-associated mutations - individuals can always fork out for a clinical test.

What proportion of people will take this DIY route? This isn't for everyone. Those wealthy enough to blithely fork out $10,000 for a medical genome interpretation, or sufficiently unwell to be able to convince their insurance company or public health system to pay for it, will by and large simply take the expensive medical route. Of the remainder, relatively few people will be sufficiently motivated to develop the background knowledge required to make sense of their genome, even if the analysis software is relatively intuitive. But for the non-trivial fraction of the population who want to know about their genomes, but don't want to pay the inflated costs associated with medical-grade sequencing - and I know this is a category that many readers of Genetic Future fall into - this will be an attractive and feasible option.

In addition, there will be advantages to the DIY approach beyond the lower cost. People who actively engage in the process of constructing useful information from raw sequence data - regardless of how intuitive the software is for doing it - will automatically learn important lessons about the nature of genetics (just as anyone who has given more than a casual glance at their own 23andMe profile has automatically learnt something important about the probabilistic nature of genetic risk factors for common diseases). They will also have opportunities to ask and answer fascinating questions that would be irrelevant in a purely medical consultation about your genome: for instance, what does your genetic information tell you about your ancestry?

They'll be able to ask these questions because they will own the data. How easy do you think it will be to obtain your raw genome sequence from your doctor to use to satisfy your own curiosity? How many forms and disclaimers will you need to sign? How many times will you need to listen to someone tell you that the data files are just too large, that the formats are inaccessible to lay-people, that your request is extremely unusual and will need to be considered for months by a hospital committee in the name of "health data privacy"? Anyone who has ever tried to get access to their own medical records will know how tedious and shrouded in unnecessary mystery this process can be; imagine how much larger the obstacles will loom when the system has the additional excuse of large, complex file formats to throw in your path.

Importantly, your genome is just one contributor to your present and future health. DIY genomics will, I hope, be part of a larger ongoing trend towards individuals taking greater personal responsibility for tracking and maintaining their own wellness - a task, incidentally, which modern healthcare systems are spectacularly ill-equipped to perform, something that seems unlikely to change substantively in the near future. As Western populations age, this broader shift of responsibility will be essential for healthcare systems to survive.

But I digress. My point here is simply this: Herper is perfectly correct that the overheads imposed (for a mixture of valid and arbitrary reasons) by medical-grade testing will ensure that clinical genomes remain expensive. But for those of us willing to learn the skills required to go outside the system, the $1000 genome is rapidly approaching. We just need to be ready to make the most of what it contains - and to reap the benefits of accessing that information as an active, engaged participant rather than a passive recipient.

sb admin Fri, 01/07/2011 - 04:10

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Why you CAN have your $1000 genome - so long as you learn what to do with it

dgmacarthur — Fri, 07 Jan 2011 09:10:00 +0000

Why you CAN have your $1000 genome - so long as you learn what to do with it

dgmacarthur Fri, 01/07/2011 - 04:10

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Bioscience Resource Project critique of modern genomics: a missed opportunity [Genetic Future]

sb admin — Wed, 15 Dec 2010 06:15:00 +0000

Bioscience Resource Project critique of modern genomics: a missed opportunity [Genetic Future]

Late last week I stumbled across a press release with an attention-grabbing headline ("The Causes of Common Diseases are Not Genetic Concludes a New Analysis") linking to a lengthy blog post at the Bioscience Resource Project, a website devoted to food and agriculture. The post, written by two plant geneticists, plays a tune that will be familiar to anyone who has encountered the rhetoric of GeneWatch UK: basically, modern genomics is pure hype perpetuated by scientists seeking grant money and corporations seeking to absolve themselves of responsibility for environmental disasters.

The post is long, but its core argument can be summarised as follows:

Genome-wide association studies (GWAS) have failed to find variants explaining much of the risk of common diseases like type 2 diabetes;
The potential hiding places postulated for the remaining "missing heritability" are implausible;
Many epidemiological studies have shown a major role for environmental factors in determining disease risk;
Studies estimating the proportion of disease risk determined by genetics using twin pairs are flawed;
Both corporations and medical researchers have incentives to prop up the notion that common diseases have genetic causes;
Therefore, the notion of major genetic causation for common diseases is a fallacy, and we should stop looking for disease genes in favour of investing in beneficial environmental changes.

These claims would be fascinating, if true. However, while the article makes some (scattered) valid points, its central claim (that the results of GWAS suggest that genetics plays little or no role in the causation of common diseases) is entirely false, and the authors rely on a combination of distortions and statistical misunderstandings to make their case.

Unfortunately the article has not simply lapsed back into the internet obscurity it deserved: over the weekend a link to the article was posted on Twitter by popular author Michael Pollan, bringing it to the attention of his ~40,000 followers. Pollan's tweet and the cheer-leading responses from his followers were subsequently picked up and blasted over at OpenHelix, leading to an exchange with one of the authors in the comments. The article was also criticised for a schoolboy statistical error by Luke Jostins, but received a qualified positive review from Mike the Mad Biologist.

So, let's take a closer look at how well the some of the claims in the article stand up.

Why was the post written?

The article itself is written in a reasonably neutral tone, which could easily fool the casual reader without a solid background in genetics (like, perhaps, Michael Pollan) into seeing it as a dispassionate critique of the field. However, it's important to read the post in the appropriate context.

In a comment over at the Huffington Post found by Keith Grimaldi, one of the authors explains the key messages and motivations of his analysis:

We have just reported that genetics now demonstratÂes that genes cannot be the cause of common diseases:

http://wwwÂ.biosciencÂeresource.Âorg/commenÂtaries/artÂicle.php?iÂd=46

That means environmenÂt must be the entire cause of ill health, i.e. junk food, pollution, lack of exercise, etc. The reason we wrote an article about human genetics (when we are a food and agriculturÂe website) is that we believe that if people live right, agriculturÂe and therefore the planet will more or less fix itself. [my emphasis]

This quote is illuminating in a number of ways. Firstly, it shows that there is no nuance in this argument: the authors aren't attempting to argue that genes play a smaller role in common disease than geneticists expected, but rather that genetics plays no role whatsoever.

Secondly, it reveals the motivations behind the post: the authors have assembled this critique, despite their acknowledged lack of expertise in the field, because they want to encourage a greater focus on behavioural and economic changes to bring large-scale environmental benefits. A noble cause, to be sure, but not one that necessarily encourages them to take a balanced approach to the discussion.

I don't mean to discount the post itself on the basis of its authors' motivations, but I do think it is important to read the piece in this context.

OK - on to some of the specific claims made in the piece.

Possible explanations for the missing heritability are post hoc and implausible

The authors claim:

A problem for all these hypotheses, however, is that anyone wishing to take them seriously needs to consider one important question. How likely is it that a quantity of genetic variation that could only be called enormous (i.e. more than 90-95% of that for 80 human diseases) is all hiding in what until now had been considered genetically unlikely places? In other words, they all require the science of genetics to be turned on its head. [italics in original]

This is complete nonsense. Indeed, the authors' question should be turned on its head: How likely is it that a technology that we know is only well-powered to find risk-associated variants that are common and have reasonable effect sizes will have found all - or even most - of the variants underlying common disease risk? If the answer to that question is "not very likely" - as it clearly is - then the authors' argument falls apart. Genome-wide association studies (GWAS) were not conducted because scientists expected them to find every disease-associated variant, but because they were a place to start with the technology that was available; the fact that a large fraction of the heritable risk remains undiscovered is not a sound reason to doubt that risk was heritable in the first place.

Some fraction of the missing heritability for complex diseases may turn out to lie in exotic candidates such as epigenetic inheritance or heritable variation in microflora, but these aren't yet required explanations. There are also perfectly mundane locations that haven't yet been explored by modern genomics, and would require absolutely zero changes to "the science of genetics" to investigate. For instance, genome-wide association studies (GWAS) conducted to date have been seriously under-powered to detect risk variants at low frequency (less than 5%) in the population, as well as common variants with individually very small effects on disease risk - yet there's no reason not to expect an appreciable fraction of the population variance in disease risk to fall into these categories. Or, again, are we expected to believe that the distribution of allele frequencies and effect sizes for disease risk variants falls entirely within the range for which GWAS conducted to date have been 100% powered to detect them?

We haven't even begun to make the most of risk variants we have already uncovered. GWAS are capable of flagging up a region of the genome linked to a disease, but typically don't immediately identify the precise genetic change responsible for that association. More detailed analyses of risk-associated regions (known as fine-mapping) allow researchers to zoom in on variants that are more tightly linked with the underlying causal change - and this alone can substantially increase the fraction of variance explained.

Variants discovered by GWAS are useless

The authors argue:

For each disease, even if a person was born with every known 'bad' (or 'good') genetic variant, which is statistically highly unlikely, their probability of contracting the disease would still only be minimally altered from the average.

Erm, no. Luke Jostins has a very handy post showing the distribution of risk prediction scores for individuals with different combinations of genetic variants associated with three common diseases: type 1 diabetes, type 2 diabetes, and Crohn's disease. Given he'd gone to all the work of collating these distributions, I asked him to do precisely the analysis the post authors describe here, and compare the predicted risk of individuals with all possible risk variants to the population average.

Here are the results for people with the average risk vs those with the highest number of risk variants:

Type 2 diabetes: 19.6% vs 41.3%

Type 1 diabetes: 1% vs 65%

Crohn's disease: 0.4% vs 99.6%

This analysis includes only variants identified by GWAS, but it's also based on a somewhat out-of-date catalogue of variants - so updating the results would increase this spread slightly further. [Explanation above edited to correct minor error in original version, which stated numbers were for lowest vs highest risk rather than average vs highest risk.]

Do the authors genuinely believe that the difference between 0.4% and 99.6% risk represents "minimal alteration", or have they just not bothered to actually look into these numbers themselves?

Strong environmental effects on disease risk argue against strong genetic effects

This argument pops up in a number of places in the article. For instance, the authors point out the apparent contradiction between twin studies suggesting that the risk of myopia is 80% heritable, whereas individuals moving from non-Western to Western countries can go from a prevalence of myopia of 0% to 80%. How can these two figures be reconciled?

The answer is that heritability is a number that applies to a specific population within a specific environment. Within white Europeans living in Western countries, who face a reasonably uniform set of environmental risk factors, around 80% of the risk of myopia is genetic. That number will obviously not apply to a population in which some individuals are moving from a low-risk to a high-risk environment, in whom the majority of the risk is primarily determined by that massive environmental difference. However, importantly, that doesn't mean the heritability estimate isn't correct for white Europeans: it just means that it shouldn't be extrapolated to other populations subject to different combinations of genetic and environmental risk factors.

There is no contradiction here, just a misunderstanding of the concept of heritability. The authors' misunderstanding should remind us of the caution that needs to be applied when thinking about heritability, and also that the existence of strong genetic predispositions to common diseases doesn't mean that environmental interventions can't be extremely effective. However, it's not a valid critique of the heritability estimates generated for common diseases.

The evidence for disease heritability from twin studies is flawed

The authors claim:

Studies of human twins estimate heritability (h²) by calculating disease incidence in monozygotic (genetically identical) twins versus dizygotic (fraternal) twins (who share 50% of their DNA). If monozygotic twin pairs share disorders more frequently than do dizygotic twins, it is presumed that a genetic factor must be involved. A problem arises, however, when the number resulting from this calculation is considered to be an estimate of the relative contribution of genes and environment over the whole population (and environment) from which the twins were selected. This is because the measurements are done in a series of pairwise comparisons, meaning that only the variation within each twin pair is actually being measured. Consequently, the method implicitly defines as environment only the difference within each twin pair. Since each twin pair normally shares location, parenting styles, food, schooling, etc., much of the environmental variability that exists between individuals in the wider population is de facto excluded from the analysis. In other words, heritability (h²), when calculated this way, fails to adequately incorporate environmental variation and inflates the relative importance of genes. [my emphasis]

As Luke Jostins has already explained at length over at Genomes Unzipped, this criticism is based entirely on a statistical misunderstanding of the methodology behind heritability studies. In fact, the sentence highlighted in bold above is completely wrong: twin-based heritability estimates use between-family variability, not within-family variability, to estimate the proportion of variation that is due to the environment. This misunderstanding completely undermines their argument against heritability estimates.

As Luke notes, there are valid reasons to be cautious about heritability estimates from twin studies - but this isn't one of them.

What this piece could have been

Mike the Mad Biologist has a post about this article, in which he describes it as having "good and bad points". I should also be charitable: although the central argument of the post (that results from GWAS suggest that genetic factors have little or no role in common disease) is completely wrong, there are valid criticisms of the excessive value that is sometimes placed on genetic versus environmental explanations of morbidity.

Stripping away the conspiracy-mongering and accusations of genetic determinism among geneticists (seriously, how can anyone working on complex diseases be a genetic determinist?), there are some nuggets of truth in the article's discussion:

The last fifteen years, coinciding with the rise of medical genetics, have seen unprecedented sums of money directed at medical research. At the same time, research on pollution, nutrition and epidemiology has not benefited in any comparable way.

[...]

This same mindset is accurately reflected in the media where even strong environmental links to disease often receive little attention, while speculative genetic associations can be front page news.

Even as a direct beneficiary of money thrown at medical genetics over the last five years, and someone who blogs entirely about news in the genetic domain, I freely acknowledge that these criticisms have merit. Genetic dissection of common disease is valuable, and will be (and indeed already has been) fruitful in generating new therapies, but it is nonetheless true that research into environmental risk factors and interventions to minimise morbidity is woefully under-funded and under-reported relative to its potential benefit.

This article could thus have been a considered, balanced and valuable critique of the imbalance in funding between research into the genetic and environmental contributors to common disease. Instead, the authors have undermined their argument by wandering into territory they don't understand, and taking an extreme position that is inconsistent with the available evidence. Perhaps they felt that polarising the debate was the only way to get attention - and indeed that approach seems to have worked - but that has come at the cost of destroying the credibility of their message. This was a missed opportunity.

sb admin Wed, 12/15/2010 - 01:15

Genomes Unzipped reader survey [Genetic Future]

sb admin — Fri, 03 Dec 2010 08:45:00 +0000

Genomes Unzipped reader survey [Genetic Future]

A reminder to anyone who reads my other blog Genomes Unzipped that we have a reader survey underway there now, which includes some questions about genetic testing experiences and attitudes towards genetics. We're closing the survey to responses this weekend, so if you're an Unzipped reader but haven't had a chance to fill in the survey, please do so now.

sb admin Fri, 12/03/2010 - 03:45

News from 23andMe: a bigger chip, a new subscription model and another discount drive [Genetic Future]

sb admin — Wed, 24 Nov 2010 07:45:00 +0000

News from 23andMe: a bigger chip, a new subscription model and another discount drive [Genetic Future]

Update 30/11/10: 23andMe has extended their 80% discount until Christmas, without a need for a discount code.

Personal genomics company 23andMe has made some fairly major announcements this week: a brand new chip, a new product strategy (including a monthly subscription fee), and yet another discount push. What do these changes mean for existing and new customers?

The new chip

23andMe's new v3 chip is a substantial improvement over the v2 chip that most current customers were run on (the v2 was introduced back in September 2008). Firstly, the v3 chip includes nearly double the number of markers across the genome, meaning that it is able to "tag" a larger fraction of common genetic variants ("tagging" means that a marker on the chip is sufficiently highly correlated with other markers that it can be used to make a reasonable guess about someone's sequence at those other markers). Secondly, the chip now includes additional custom markers targeting specific variants that the company thinks will be of interest to its customers.

The technical details: the v3 chip is based on Illumina's HumanOmniExpress platform, which includes 733,202 genome-wide markers. The company has also added around 200,000 custom markers to the chip (vs ~30,000 on the v2 chip). We don't yet have full details on what those custom markers are, but there's a summary of the improvements over the v2 chip in the press release:

Increased coverage of drug metabolizing enzymes and transporters (DMET) as well as other genes associated with response to various drugs.
Increased coverage of gene markers associated with Cystic Fibrosis and other Mendelian diseases such as Tay-Sachs.
Denser coverage of the Human Leukocyte Antigen region, which contains genes related to many autoimmune conditions.

Deeper coverage of the HLA is particularly welcome - variants in this region are very strongly associated with many different complex human diseases (including virtually every auto-immune disease), and the v2 chip was missing several crucial markers.

The addition of more rare variants associated with Mendelian diseases like cystic fibrosis is entirely unsurprising, but the devil will be in the details: in the arena of carrier testing 23andMe is up against the extremely thorough and experimentally validated platform offered by pre-conception screening company Counsyl. It will be very interesting to see the degree to which 23andMe focuses on the carrier testing angle in their marketing of the v3.

More power for imputation

From the perspective of those of us simply interested in squeezing as much information as possible out of our genetic data, the v3 chip is a welcome arrival. The additional markers present on the chip will substantially improve the power of genotype imputation - that is, making a "best guess" of our sequence at markers not present on the chip using information from tagging variants.

The HumanOmniExpress platform has some decent power here: in European and East Asian populations, 60-70% of all of the SNPs with a frequency above 5% found in the 1000 Genomes pilot project are tagged by a marker on the chip (in this context, "tagged" means "has a correlation of 80% or greater"). In effect, that means that being analysed at the one million markers on this chip allows you to make a decent inference of your sequence at around another 4.5 million other positions in your genome.

At the recent American Society of Human Genetics meeting, 23andMe presenter David Hinds suggested that the medium-term future for 23andMe rested not in moving to sequencing, but rather on expanding the role of genotype imputation. The new chip will certainly help with that. However, it's worth emphasising that imputation is not a replacement for sequencing: it is only accurate for markers that are reasonably common in the population, meaning that it will miss most of the rare genetic variants present in your genome.

However, improved imputation with the extra markers on the v3 chip will mean that 23andMe should be able to do a decent job of predicting customer genotypes at the positions we currently know the most about - those arising from genome-wide association studies of common, complex diseases. I expect that many customers will see changes to their disease risk profiles as a result of the move to the new chip.

Over at Genomes Unzipped, we've already been looking at various approaches to imputation from our 23andMe v2 data, and we'll put a post together soon looking at how this will improve with content from the v3 chip.

The new product strategy

There are two interesting things that 23andMe has done with the new product line: firstly, it has reversed the transient division of its products into separate Health and Ancestry components; and it has introduced a subscription model in which customers pay $5/month for updates to their account as new research findings become available (previously, customers paid a flat purchase fee and were then entitled to free updates).

The recombining of the Health and Ancestry products into a single Complete package is an extremely interesting move. As Dan Vorhaus notes, the previous separation of the two product lines was plausibly interpreted as a way for the company to pre-empt the possibility of a regulatory crackdown by the FDA: if regulators hammered the company's ability to offer health-relevant tests directly to consumers, 23andMe could easily switch to its Ancestry product to maintain a revenue stream.

In the currently uncertain regulatory environment, the decision to reverse this division is an unexpected one. It certainly appears that 23andMe - flush with cash following a successful $22M funding round - is somewhat more confident than I am about the regulatory future for health-relevant genetic tests; I hope that confidence turns out to be warranted.

Subscription fees: good for customers

The decision to add a subscription fee may prove unpopular with customers (and has already received a qualified thumbs down from blogger Dienekes, albeit for perfectly sensible reasons). However, a business model based on providing continuous product updates that customers don't pay for has never really looked like a viable long-term business model.

I personally see a subscription model as a positive move: it provides a steadier revenue stream for personal genomics companies, which means less focus on splashy discount drives. It also provides more of a financial incentive for the company to improve the ongoing experience of customers: under the current deal customers are locked in for the first 12 months, but after that 23andMe will need to convince them that it's worth continuing to pay for additional content and features.

Other personal genomics companies (e.g. Navigenics) have long relied on some form of a subscription model, but typically at a higher cost. I think 23andMe is hitting a pretty reasonable price point here: I suspect $60/year would be seen by most customers as a fair price.

OMG discount!

That doesn't mean that 23andMe has abandoned the discount drive approach just yet, of course: they're currently offering v3 kits for just $99 (vs the retail price of $499), which must be purchased along with the previously mentioned 12-month subscription fee of $60. Non-US customers can also expect a ~$70 postage fee, based on comments on Twitter.

Anyone who missed out on the DNA Day sale and is keen to take advantage of the v3 content would be well-advised to get in quickly. The discount code is B84YAG.

sb admin Wed, 11/24/2010 - 02:45

Categories

Social Sciences

Why I'm releasing my genetic data online [Genetic Future]

sb admin — Tue, 12 Oct 2010 06:45:00 +0000

Why I'm releasing my genetic data online [Genetic Future]

Back in June I launched a new blog, Genomes Unzipped, together with a group of colleagues and friends with expertise in various areas of genetics. At the time I made a rather cryptic comment about "planning much bigger things for the site over the next few months".

Today I announced what I meant by that: from today, all of the 12 members of Genomes Unzipped - including my wife and I - will be releasing their own results from a variety of genetic tests, online, for anyone to access. Initially those results consist of data from one company (23andMe) for all 12 members; deCODEme for one member; and Counsyl for two of us (my wife and I). As the project proceeds, we plan to obtain and release the results from a far wider range of genetic tests, up to and including complete genome sequences.

In all, the group is currently releasing over 7 million pieces of genetic data mined from our own genomes. Anyone can download the data in raw form, or view it on a custom browser that two of the group assembled using the open-source JBrowse software. Already the data is being used: blogger Dienekes yesterday published an analysis of our ancestry using his own program, EURO-DNA-CALC.

We have plenty more planned over the next few weeks, including discussion of the ethical issues associated with releasing data publicly, especially given the potential impact on family members. We'll also be presenting analyses of our own data: many of us are active researchers in genetics, and relish the opportunity to apply our research tools to our own genomes. We'll be releasing software code allowing others to run the same analyses on their own data.

So, why on Earth are we doing this?

I summarised some of the key motivations for members of the group in my Unzipped announcement post:

we want to share the results of scientific analysis of our own genomes, and as proponents of open data access most of us believe that doing good science means releasing complete data for others to investigate;
we hope that releasing our data publicly will help to guide useful discussions about genetic privacy and the benefits, risks and limitations of genetic information in general;
many of us believe that the ideal resource for genetic research is large open-access, non-anonymous research databases such as the Personal Genome Project, and that sharing linked genetic and trait information openly with the wider community is a public good - and we hope that our own experiences will encourage others to participate in open research projects;
we all believe that many of the fears expressed about the dangers of genetic information are exaggerated, and see this project as an opportunity to have a constructive public discussion about the truth behind these fears;
given the ease with which a dedicated snoop could obtain genetic information surreptitiously (via shed skin, hair or saliva, for instance), some of us argue that the whole notion of genetic privacy is illusory anyway - while releasing our data online makes it easier for people to get hold of it, this is a difference of degree rather than kind.

I wanted to spend a bit of time here expanding on that third point, as this is probably my own primary motivation for engaging in the project.

Any researcher working in genetics or genomics will be all too familiar with the cumbersome bureaucratic obstacles associated with subject privacy and anonymity. Under the traditional research model subject anonymity and data privacy must be protected fiercely, and that leads to substantial hurdles in two key areas: firstly, data sharing between researchers is hindered by the need to ensure that data privacy is maintained; and secondly, layers of protection on subject anonymity mean it is extremely difficult to return research results to participants, even when those results might have health implications.

This is not to say that huge advances in data access have not been made over the last decade, particularly in the field of genomics. Both individual researchers and funding bodies (notably the Wellcome Trust and NIH) have done a commendable job of ensuring that many large genomics data-sets are made available to other researchers through large databases and data access agreements.

However, can we go further? Researchers such as George Church advocate a bold alternative model: recruit research participants who are willing to share their data completely openly with the world. Find large enough numbers of people willing to sacrifice their privacy for public good, and you suddenly have an amazingly powerful resource: a data-set that can be analysed by any researcher in the world with access to the internet, including participants who can play an active role in the research process.

It can't be emphasised enough just how powerful such a resource would be. Right now, virtually all human genetic and medical data is effectively locked away behind tight consent agreements. That means a given data-set only has a certain number of eyes passing over it, with a restricted circle of expertise; one cohort's data might contain valuable insights into the mechanisms by which cholesterol affects heart disease, but if the researchers holding the keys are eye specialists those will probably never be uncovered.

Science moves fastest when people from diverse backgrounds are allowed access to rich data-sets. The closer we hew to the traditional model of tightly restricted access to human data, the slower we will uncover the associations we need to move into the era of personalised, evidence-based healthcare.

Are there enough people in the world willing to forego their privacy in the name of science? That remains to be seen, but flagship studies like the Personal Genome Project - which seeks to recruit 100,000 volunteers willing to share their genomes and clinical data with the world - are already suggesting that this number is far higher than many would have expected. However, visceral opposition to the idea of releasing such information - based often on an exaggerated sense of the power of genetic data, or its potential for abuse - continue to hold sway over the vast majority of the public.

We're under no illusions here: the data from the 12 of us in Genomes Unzipped aren't in and of themselves of tremendous scientific value. However, if we can get people starting to think about the genuine public good that can be achieved by sharing their data with science, and to weigh that good against a realistic sense of the potential harms, then the project has been a success.

Edited 13/10/2010 to clarify that major progress has been made in data-sharing agreements over the last decade, especially in genomics - I apologise to anyone who interpreted my views as minimising the work that has been done in this area.

sb admin Tue, 10/12/2010 - 02:45

Categories

Medicine

The FDA doesn't plan to regulate access to raw genetic data; and context for Gutierrez scare-mongering about ovary removal

dgmacarthur — Mon, 09 Aug 2010 07:30:00 +0000

The FDA doesn't plan to regulate access to raw genetic data; and context for Gutierrez scare-mongering about ovary removal

In my previous post I quoted from Mary Carmichael's excellent interview with two officials from the FDA, Alberto Gutierrez and Elizabeth Mansfield (part of her fantastic week-long DNA dilemma series, which you should read in full if you haven't already). There are numerous nuggets of gold tucked away in this interview that warrant further analysis, and I wanted to highlight a few in more detail. For a more complete dissection I'd recommend Keith Grimaldi's post commenting on the whole interview.

I wanted to focus on two crucial tidbits unearthed by Carmichael: the attitude of the FDA towards the release of raw genetic data, and the context for horrendous scare-mongering quotes used by Gutierrez in previous mainstream media articles about direct-to-consumer genetic testing.

The FDA says accessing raw genetic data should not be regulated
This is great news for those of us interested in ensuring that people who wish to explore their own genome can do so without excessive bureaucratic intervention:

MC: Okay ... I want to move on to whether the issue with direct-to-consumer is actually providing data to people, or is it the interpretation algorithms these companies are using? So, would a company need to be approved just to provide a raw SNP list to people?
EM: They would if they made medical claims about that data. If they don't make any medical claims about that data, then they're free to provide information as far as we're concerned.

In other words, the FDA has stated on the record that if a company offers to sell you your genome sequence without interpretation, they can do so without FDA intervention. And if you then wish to take that genome sequence and run it through any of the growing list of open-access tools for interpretation (such as Promethease), you're free to do so; many of these are fortunately hosted well beyond the reach of the FDA.

Gutierrez confirms that his horror story about ovary removal wasn't due to a direct-to-consumer genetic test
Alberto Gutierrez has repeated an anecdote about women removing ovaries following test results in at least two separate mainstream media articles, both of which were written primarily about direct-to-consumer companies. The implication of Gutierrez's quotes was thus that these incidents were a result of DTC tests. Here's the first example, in a story by Andrew Pollack in the New York Times:

The F.D.A. is now clearly deciding in favor of regulation, saying the tests of disease risk can have medical consequences.

"It is not unknown for women to take out their ovaries if they are at high risk of ovarian cancer," Dr. Gutierrez said.

And again, in Rob Stein's piece in the Washington Post (which is also problematic for other reasons):

"It's come to the point where really there's a need for some oversight," said Alberto Gutierrez, who heads the FDA's Office of In Vitro Diagnostics. Results from questionable tests can be unnecessarily alarming, Gutierrez said, adding that some women have undergone surgery, for example, based on tests that purport to gauge the risk for ovarian cancer.

"We know of reports of people who have found a test, found a doctor that is willing to order the test since they are so afraid of the disease, and even removed ovaries based on questionable results," Gutierrez said.

Neither of the reporters writing these two stories bothered to seek clarification about the details behind these anecdotes - for instance, whether they were actually due to tests offered directly to consumers. Now Carmichael has asked that question, and the answer is illuminating:

MC: Alberto, I had heard a story, I believe it was in Rob Stein's article in [The Washington Post], about these women who were having prophylactic oophorectomies on the basis of direct-to-consumer genetic results that were "questionable."
AG: That's a little bit taken out of context in the sense that it's not based on the direct-to-consumer [model]. The cases we heard of were based on lab-developed tests that were not properly validated. What I did say was that even though 23andMe doesn't make a direct claim as for ovarian cancer, they do provide information that links what they are giving the consumer to ovarian cancer.

MC: So that's an example of where the interpretation is about pointing to a medical paper.
AG: It's more than that. They interpret the medical paper for them ... Ovarian cancer is called the "silent killer." People actually don't know they have it until it's too late. And women that are high risk a lot of times choose to have their ovaries removed because they are afraid that it may not be caught in time. There's no diagnostic test for it. So the tests that we have seen--there was one that was taken off the market because of FDA action ... We knew that in those cases most women who were being operated on actually were likely to be negative for ovarian cancer ... The one we heard most about originally, it was a test called OvaCheck that was going to go to the market, and we believed it was not well characterized and it was going to create problems. It never made it to the market, and then in 2008 another one made it to the market called OvaSure, and the FDA wrote LabCorp a warning letter ...

So now we know - the alarming stories were not a result of direct-to-consumer genetic testing. Indeed, neither of these examples are about predictive genetic tests at all - both OvaSure and OvaCheck are based on the use of protein biomarkers in blood to identify the presence of ovarian cancer - and yet both Rob Stein and Andrew Pollack inserted Gutierrez's quotes into stories that otherwise referred almost exclusively to direct-to-consumer genetic testing.

Whether this was due to a lack of context provided by Gutierrez, or simply sloppy reporting by Stein and Pollack, is currently unclear. Either way, it was inexcusable - and given both stories emerged at a time when the media and regulators were hunting for excuses to criticise the DTC genetic testing industry, there's little question that these out-of-context quotes had an impact.

The DTC genetic testing industry needs change: a purging of the companies operating at the disreputable end of the spectrum, and a general tightening of operating practices to ensure that raw data are accurate and that customers are given appropriate information to interpret their results. This change should be brought about by careful, light-touch regulation commensurate with the actual level of risk posed by these tests - which is very little, according to the data currently available. What is not needed is shameless scare-mongering by regulators and reporters seeking to make a splash.

Serious kudos to Mary Carmichael for asking the hard questions, and getting some real answers - no easy task when your subjects are FDA bureaucrats.

dgmacarthur Mon, 08/09/2010 - 03:30

Tags

"the FDA has stated on the record that if a company offers to sell you your genome sequence without interpretation, they can do so without FDA intervention"

And here is the pickle: if you're going to build a business you would be a fool to trust the FDA. Remember, FDA was for 23andMe before it was against it. Given the state of legal flux the US healthcare system is in do you really want to take the risk of betting millions on what some bureaucrat said in an interview? Is that a solid enough base on which to rest a business plan and the lives and families of your team? Do you really want to put yourself at the mercy of Gutierrez's whims, or should we call him Madame Ovary?

@fdsa: I think raw genetic data is a safe bet. It's not just a matter of whether the FDA could walk back Mansfield's statement; raw genetic data is simply outside of the FDA's mandate. I could still see companies getting in trouble if they tried to get too cute though. Say, if they tried offering just the minimum sequence/snp data needed for specific diagnostic tests as a product, as opposed to just a big wad of data that has a little bit that's medically relevant interspersed with a whole lot that isn't. In the first case, it's pretty arguable that they are still specifically selling diagnostics and just changing the business model in an attempt to avoid regulation.

In any case, I like the raw genetic data business model more. Your data won't change over time, but the decisions on which parts are informative and how those parts should be interpreted certainly will.

Then why isn't the FDA regulating Fortune Tellers and Palm Readers? They give people advice which leads them to make lifestyle changes like changes in diet, healthcare, pending doom etc. that are clearly fraudulent. The FDA does have some usefulness, but this is a waste of our taxpayer money to unfairly clamp down on what is clearly an emerging and important new tool for all of us.

The FDA, stifling innovation since 1906.

It's unclear to me whether the ovary-removal anecdotes -- now seen to be connected to the OvaSure and OvaCheck immunoassay LDTs -- are reflective of actual, documented patient experiences, or not.

Ovasure was also another FDA joke. Validation at Yale wasn't good enough for them.

Well (shameless self-promotion alert), in my book I describe the frustration of having one's spouse receive high CA-125 levels and the inability of the gyn-onc community to interpret them (not that they don't try in good faith). I also discuss the allure of magic diagnostic bullets such as OvaSure/OvaCheck, whose clinical validity remain in question, at least insofar as I know. So, two points:

1) Daniel is right: context is everything. These are NOT DTC tests, but "conventional" would-be dx that presumably prompted Dr. Gutierrez to make his comments and for FDA to keep the ovarian dx products off the market. This should have been made explicit in the stories.
2) What's good for the goose: I don't hear people pissing and moaning publicly about CA-125 or PSA the way they get their panties in a wad about consumer genomics, despite the fact that the former are used by orders of magnitude more people than the latter.

Protecting consumers from their own genetic data will come at a cost

dgmacarthur — Thu, 29 Jul 2010 07:30:00 +0000

Protecting consumers from their own genetic data will come at a cost

(This is an edited excerpt from an op-ed piece I just wrote for Xconomy, posted here as I think it provides some nuance on my views on regulation of genetic testing that was lacking from my post last week.

Some context for new readers: a Congressional investigation into the direct-to-consumer (DTC) genetic testing industry last week left a sour taste in the mouths of many observers of the embryonic industry; it was a vicious, one-sided affair, starring a biased report on a "sting" operation performed by the US Government Accountability Office. Along with other recent moves by the FDA, it potentially sets the scene for draconian regulation to be laid down on the industry. Here I argue that other, more careful approaches are the best way forward.

For more discussion from multiple viewpoints on the regulatory battle ahead, check out the posts by my co-authors on Genomes Unzipped and the ensuing comments threads: Caroline Wright argues that genetic data provides educational opportunities that should not be legislated away, and Jeff Barrett and Kate Morley argue that different standards should be applied to medical and non-medical tests.)

The costs of regulation
It would be all too easy to use the false claims and unethical behaviour depicted in the GAO report to justify a whole-sale FDA crackdown on the direct-to-consumer genetic testing industry, and that was certainly the flavour of the Congress proceedings. However, such a move would be short-sighted, and would ultimately harm consumers more than it protected them.

Regulation comes at a cost: each additional barrier thrown in the path of companies means increased costs to consumers, reduced competition (as entrepreneurs move into less burdensome fields), increased lag times between new discoveries and finished products, and ultimately weaker innovation. In some cases these costs are justified, which is why we tolerate a massive regulatory burden on pharmaceutical companies despite the resulting higher price of drugs. However, we must insist that each new regulatory obstacle be justified by the protection it provides to consumers.

Reputable DTC companies are already bound by regulation: their testing laboratories must be certified under Clinical Laboratory Improvement Amendments (CLIA) standards, which govern the technical accuracy of results. The false claims and unethical marketing highlighted in the GAO report would also seem to fall under the mandate of the Federal Trade Commission (FTC), who have already made some moves towards educating consumers about DTC genetic tests. It would seem appropriate to consider whether strengthening these existing mechanisms would serve consumers better than introducing FDA regulation.

Excessive regulation would devastate the industry, and that would harm more than just the companies involved. For all its faults, the DTC industry is currently an engine of innovation for technologies that will be crucial to the coming era of genomic medicine, such as intuitive interfaces for exploring large-scale genetic data. Close the industry down and those innovations will also disappear, with much broader negative consequences than the FDA or Congress appears to realise.

A way forward
There are alternatives to the paternalistic approach of locking tests away from consumers unless they're deemed to exceed some FDA-defined threshold: for instance, empowering consumers to make their own informed decisions about genetic testing products. Coupled with strengthening of the existing CLIA regulations and a boosted FTC mandate to purge the industry of scammers, such an approach would help to protect genetic test customers without destroying the innovative DTC industry.

As Dan Vorhaus and I have previously argued, the key to this approach will be increasing the transparency of the industry. As a starting point, creating a mandatory database of genetic testing products containing information about the scientific basis of companies' claims - preferably by building on the NIH's proposed Genetic Testing Registry - would provide a platform for consumers to make an informed comparison of reputable tests. It would also provide an even playing field for public critiques of the markers and algorithms used by each company, spurring the industry as a whole towards improving their products.

Crucially, this database would need to be accompanied by education of both consumers and clinicians about the value and limitations of existing genetic tests. These are complex issues, and challenging to convey to consumers without a PhD in statistical genetics; but as we move into an era where whole genome sequences move from luxury goods to cheap commodities, they are issues we must learn how to communicate - and soon.

dgmacarthur Thu, 07/29/2010 - 03:30

Tags

commercial genetic testing

direct-to-consumer genetic testing

Categories

Shipping spit tubes to China or India is pretty easy and getting the data back is even easier. The only effect I see of all this possible regulation is the killing of American jobs and companies and sending the work off-shore. Add to that, you can get just as good information from a detailed family history, and I think any concern for the need of ANY government regulation looks pretty stupid.

What a bunch of scammers. When Venter says that it's decades or more before "genomics medicine" is anything but a scam, you know what's going on here.

Cry me a river over "over-regulation". That's the whine you always here from folks who are running a grift.

Can you provide a link to Venter's quote, for context?

Maybe @frog is hyperbole-ing this
http://www.nature.com/nature/journal/v464/n7289/full/464676a.html

"Yet there is still some way to go before this capability can have a significant effect on medicine and health" Venter on Genomics use in medicine and health....

If so, that's some pretty impressive hyperbole...

Mind you, Venter uses pretty strong language in his Spiegel interview... http://bit.ly/ana9aT

Some extracts:

Venter: I have a slightly increased risk for Alzheimer's disease. But it impresses me little because I could have dozens of other genes that counteract it. Because we do not know that, this information is meaningless.

and:

Venter: And what else have I learned from my genome? Very little. We couldn't even be certain from my genome what my eye color was. Isn't that sad? Everyone was looking for miracle 'yes/no' answers in the genome. "Yes, you'll have cancer." Or "No, you won't have cancer." But that's just not the way it is.

SPIEGEL: So the Human Genome Project has had very little medical benefits so far?

Venter: Close to zero to put it precisely.... we have, in truth, learned nothing from the genome other than probabilities. How does a 1 or 3 percent increased risk for something translate into the clinic? It is useless information.

Daniel -- you suggested here and previously that "(CLIA) standards . . . govern the technical accuracy of results." As far as I can tell, that's not true. CLIA governs what goes into the lab, and how the lab is run, but it doesn't evaluate the accuracy of the resulting SNP calls.
Lee

Hi Lee,

CLIA certification requires that a lab fulfil requirements relating to quality control, personnel qualifications, records maintenance, and proficiency testing; basically, to demonstrate that it has systems in place to ensure consistent, high-quality data. Would it help if I'd said "analytic validity" rather than "technical accuracy"?

Ventner says whatever is popular. Hates it when he's out of the spotlight. Talked idly with Anne and Sergey about googling their genes in the Google Story book but Anne ended up working with Linda. So Ventner gets his revenge by funding Pauline Ng to rip Anne a new one in Nature.

When the genome came out he also promulgated some stuff about no race or ancestry in the genome. Then a few years later his institute is putting out exquisitely color coded pca plots like every other scientist.

A sad day for personal genomics

dgmacarthur — Thu, 22 Jul 2010 16:00:00 +0000

A sad day for personal genomics

(Cross-posted to Genomes Unzipped.)

Today's US Congress Committee on Energy and Commerce hearing into the direct-to-consumer genetic testing industry was a vicious affair. Representatives from testing companies 23andMe, Navigenics and Pathway faced a barrage of questions about the accuracy and utility of their tests, made all the worse by the fact that many of the Committee's members seemed unable to distinguish between the more responsible companies in the field and the scammers and bottom-feeders. (I watched by web-cast, which I can't yet track down a copy of online; you can read the written testimony of the speakers here.)

And the news for direct-to-consumer companies just keeps getting grimmer: the star attraction of the hearing today was a new report from a sting operation by the US Government Accountability Office (PDF), which details the results of anonymous purchases of kits from four DTC testing companies as well as assessments of marketing from 11 other companies approached by the GAO "both by phone and in person" without purchasing kits. While the companies are listed as anonymous numbers in the report, they were revealed in the hearing as (1) 23andMe, (2) deCODEme, (3) Pathway Genomics and (4) Navigenics (the remaining 11 remain nameless). The report details a litany of complaints - ranging from the flimsy to the serious - about the marketing, reporting and scientific basis for the companies' operations.

Following hot on the heels of the two-day FDA meeting on lab-developed tests (see summaries from Dan Vorhaus here and here) and the recent warning letters sent to 14 more genetic test providers, this is a stunning blow to the nascent personal genomics industry.

But wait, there's more

And it gets much, much worse: the report includes covertly taped conversations between GAO employees and several DTC companies, which I've embedded below. In this video, the company offering breast cancer advice is apparently Navigenics, and the company enthusiastically promoting non-consensual DNA testing for a customer's fiance is Pathway Genomics. It seems safe to assume that the remaining companies on the tape aren't members of the first four (reputable) testing companies, but rather of the still-anonymous 11.

Read the rest of this post at Genomes Unzipped >>

dgmacarthur Thu, 07/22/2010 - 12:00

Tags

So I'll ask again. How should DTC testing be regulated, if at all? You agree that even the big guys have some problems that need correction, as evidenced by some of those recorded clips, right?

What's the best way to weed out the scammers and make sure the remaining companies act responsibly, especially when it comes to health related testing?

Apologies if you've addressed this question before. If so, I'd appreciate a link. Thanks!

Hi qetzal,

Dan Vorhaus and I have some suggestions here.

A mandatory database of genetic tests to support informed decisions by consumers, continued refinement of CLIA to ensure analytic validity, and active enforcement against companies that make false claims via the FTC.

sad day, indeed. Bureaucrats 1 Innovators 0

A mandatory database of genetic tests to support informed decisions by consumers, continued refinement of CLIA to ensure analytic validity, and active enforcement against companies that make false claims via the FTC.

So in this model, would tests that yield information relevant to medical diagnoses be required to get CLIA certification before being marketed?

So in this model, would tests that yield information relevant to medical diagnoses be required to get CLIA certification before being marketed?

Yes. That's already true for all of the major personal genomics companies.

Yes. That's already true for all of the major personal genomics companies.

CLIA approval of the lab doing the testing, yes. and I'd guess that would include many tests for analytical validity (the 99.9% you brought up in your post).
But for it to be useful to the consumer, what's needed is CLIA certification of the clinical utility and validity of each test offered. I.e., not just verification that "you have this pattern of alleles/SNPs", but verification that "this pattern of alleles is highly associated with this condition", etc.
Otherwise the database could end up being pretty misleading to consumers.

Daniel and Dan,
The registry and database does nothing to prevent poor medical advice like that given over the phone. I think it Navi's case it might have been one of their genetic counselors too. Which would be a huge travesty....

Medical testing IS Medical Testing. BRCA, PGx these are REAL things. Why won't you guys admit that and move on here?

Because they are medical tests, they should be regulated so. And those doing the interpretation of medical tests are practicing medicine and should be regulated so.

Please tell me how identifying a BRCA carrier is not a medical test? Even if you do, I ask you to ask a physician you trust whether or not your argument is worthy.

This day was coming the moment they put BRCA on their Chip...And then jumped into PGx.

Not a sad day. A day created by and for DTCG because of their flagrant unwillingness to work with physicians in favor of "Fun and Revolution"

The public still (barely) trusts physicians. I don't think they will ever trust DTCG again.

-Steve

Daniel,

Thanks for the response, but I agree with hibob. I don't see how a mandatory registry addresses the key issue of whether a given test is clinically valid. Are you content to leave that up to a company's discretion? Would you accept the same approach for pharmaceuticals?

I'm far from convinced that's an adequate approach. At the same time, I don't think a person should be required to go to an MD to have genetic testing done. I'm just not sure what the happy medium is here.

Steve,
Perhaps testing BRCA does constitute "medical diagnosis". Perhaps it is fair and in the public interest for the FDA to impose regulations so that genetic tests for the BRCA gene are Physician ordered only. But please let us still have unrestricted access to the half a million other SNP's that are tested by companies such as 23andme and don't constitute "medical diagnosis".

I watched the live webcast yesterday and was frankly appalled at the biased way in which the "evidence" found by the US Government Accountability Office was presented. I would hope that the GAO will in due course release the full recordings and transcripts of all their telephone conversations. (I would hope that there is a US equivalent of the UK Freedom of Information Act and it will be possible to request this information.) It would appear that the two DTC companies in the video are Navigenics and Pathway Genomics. Both these companies now require consumers to order their tests through a doctor and/or with advice from a genetics counsellor. The GAO were seemingly unable to find any evidence that 23andMe and deCODEme, the two companies who do sell their tests direct to consumers, were misinforming their customers over the telephone. 23andMe, Navigenics and Pathway were all asked to testify at the hearing. They were not given the chance to review the GAO evidence beforehand but were asked to comment on these findings on the spot. In the hearing Ashley Gould the counsel for 23andMe revealed that the company actually approached the FDA for advice three years ago before they even launched the company. If the FDA were so concerned about the 23andMe test why did they not work with 23andMe at the time rather than hounding them in such a public way now? Misleading marketing and advertising can be a problem with all companies. In the UK we have an Advertising Standards Authority and an Office of Fair Trading which oversee such issues. Is there no such equivalent in the US? There are indeed fraudulent companies which need regulating and investigating. I find it incomprehensible that the Congressmen and the FDA are focusing all their attentions on the responsible companies like 23andMe while seemingly ignoring the fraudulent scam companies such as the supplement companies in the video. Why were representatives of these other companies not called to give evidence? Genetic tests are predictive not diagnostic. The average consumer is only going to test with one company and simply could not afford to test with multiple companies so the different reporting methods are unlikely to be such a big issue. A patient could just as easily consult a number of different doctors and be given different diagnoses and prescribed different drugs. A predisposition to breast cancer could easily be uncovered by researching your family history. Perhaps the FDA should also be regulating family history research!

Hi guys,

I think we should move the comment thread over to Genomes Unzipped - things are moving pretty fast there.

Why isn't anyone worried about all the MD's and their disinformation or ignorance or the greed powering their decisions? The entire government has a white coat syndrome: MD's exempt from stupid.

If they only knew.

Murphy is worried about his profession's rep. He should be. They Rx snake oil and call it health care. They learn from drug reps and call it education. Recent conversation with a Stanford cardiologist is telling: he wants to buy a house here in Palo Alto so he will do what procedures bring him the biggest bucks to get there the quickest.

Put a wire on me. I'll prove the danger is in the medical profession a lot more profoundly and a lot more dangerously than 23andme.

"Women are cash cows. Without them, I'd have nothing. They seek more unnecessary medical care than anyone else." Another precious MD no one will touch. Who is going to go after the real whores of the profession? And let people have their own damn data if they want it? Who watches the watchers?

@AB
ad hominem attacks only work when you have real evidence, which then makes them no longer ad hominem fallacy. Do some work like the GAO to flay doctors.

Next time....

AMA wins again!
Freedom loses.
again.

Labcorp 0wNz the guvermint!