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A few hours after the interview, the agency wrote in an email that it had "not asked Illumina to stop, but if they continue to make these chips available, [it] could explore other regulatory action."

Daniel, you do yourself a disservice, your scoop is completely intact. Re-read the quote above. This official FDA email to Daniel Vorhaus says that they threatened "other regulatory action" if Illumina "continue[s] to make these chips available".

Those words were carefully chosen and it's pretty cut & dry. The FDA is surprised that this was publicly aired because their usual strategy is invisible backroom abuse, so they're now clouding the language and walking it back a bit, but what they did is clear.

Consider the phrasing. Surely Illumina isn't going to risk having the FDA explore "other regulatory action". A warning letter alone can take hundreds of millions of dollars off a stock price and tarnish their name. And forget about it if the FDA decides to send in inspectors or hold up approvals of all the things Illumina has in the FDA pipeline.

Gutierrez didn't want to admit in so many words that they made this threat during the interview, but make no mistake they knew what they were doing.

Illumina was only in the DTC space because it was (emphasize WAS) a growth market for them. Doubt Jay Flatley wants to screw 23andMe, but the FDA has a gun to his head and he has a responsibility to his employees. Even though everyone knows that Gutierrez and Shuren have gone crazy, he can't let Illumina be killed for 23andMe's imagined sins.

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

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Read the full article at Xconomy.

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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.

Consumer genetics needs more transparency, not excessive regulation

dgmacarthur — Fri, 25 Jun 2010 05:30:00 +0000

Consumer genetics needs more transparency, not excessive regulation

An excerpt from an article I co-wrote for Xconomy with Genomics Law Report's Dan Vorhaus - link to the full article below.

Are you ready for consumer genetics? Is your government?

Recent announcements of federal investigations into the budding direct-to-consumer (DTC) genetic testing industry suggest that authorities are preparing to increase regulation of companies offering consumers access to their own genetic data. However, rather than rushing in to clamp down on the industry, regulators should slow down and focus, first, on understanding this complex field.

An increasing number of individuals are exploring their genetic information using tests purchased directly over the Internet. For between $100 and $1,000 consumers can purchase a saliva collection tube, spit in the tube, and mail it back to the company. A few weeks later the results are available online. One DTC genetics company, 23andMe, recently announced that it had provided its test to over 30,000 customers.

Genetic tests can provide the consumer with personalized information ranging from eye color, to ancestry, to risk of common diseases such as diabetes. Many companies include all of these traits and more in a single product examining hundreds of thousands of genetic markers. For the moment, these tests are available to anybody with a computer and a sense of curiosity. But that could all change.

dgmacarthur Fri, 06/25/2010 - 01:30

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op-ed

transparency

Transparency beats regulation in the financial world too (^_^)

How can you have more transparency without regulation? It's human nature for people to hide things, especially when profits and shareholders are on the line. Regulation leads to transparency in my opinion.

I am with Gene. Transparency does not exist of its own due to the high moral characters of the business owners of genomic testing companies because they really believe in it. Yes I am being sarcastic. Transparency only exists because it is forced by regulation. It is silly to let business people with their own selfish needs override public security issues, and fears that these folks are just taking them for a ride, and scamming them for their money. PT Barnum: There is a sucker born every minute, is the usual business credo.

23andMe research article finally published

dgmacarthur — Fri, 25 Jun 2010 04:30:00 +0000

23andMe research article finally published

In October last year I reported on a presentation by direct-to-consumer genetic testing company 23andMe at the American Society of Human Genetics meeting in Honolulu, in which the company described results of genetic association studies performed using combined genetic and survey data from their customers. The results of their study include replication of several known associations for traits like hair colour, eye colour and freckling, as well as the discovery of previously unpublished associations for things like asparagus anosmia (the ability to smell urinary breakdown products after eating asparagus) and photic sneeze (the tendency to sneeze when entering bright light).

This research has finally been published in PLoS Genetics, one full year after the manuscript was originally submitted to the journal on June 22, 2009. In a separate article, PLoS editors Greg Gibson and Gregory Copenhaver explain that this delay was due to six months of investigation into the issues of ethical review, participant consent and data access in the context of 23andMe's research. As a result of this process, 23andMe announced yesterday that all of its research will now be conducted under the auspices of a formal IRB.

In a post on her blog, 23andMe co-founder Linda Avey describes the publication as "historic", and I think this is no exaggeration. 23andMe has gathered an unique, actively engaged participant base of customers willing to contribute their data to the company's research efforts, many of whom (myself included) are excited to see their information being used to identify entirely novel scientific findings.

While it's easy to scoff at the traits assessed in this paper, the company is beginning to assemble a research base with growing power: the company tells us that of its 50,000 customers, 29,000 have participated in research surveys, enabling over 650 simultaneous genome-wide association studies. And because many of the company's customers are actively engaged, there's room for promising associations to be chased up with more detailed surveys and longitudinal studies. The power and flexibility of this approach would be the envy of many an academic researcher.

In a brilliant article on Google's Sergey Brin this week in Wired, Thomas Goetz illustrates the utility of the 23andMe approach with a simple example: a massive study of the association between glucocerebrosidase mutations and Parkinson's disease published late last year, the key finding of which was successfully replicated by analysis done by 23andMe on their Parkinson's recruits.

After a month of bad news for the personal genomics industry, it's good to be able to report something positive, and this certainly is positive: it's a demonstration of what can be achieved when research participants are given an opportunity to engage in research on their own data. I can only hope that academic research groups are paying attention, and thinking about ways they can leverage the same effects.

dgmacarthur Fri, 06/25/2010 - 00:30

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consumer-driven research

http://www.nature.com/ng/journal/v42/n7/full/ng.608.html

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Social Sciences

Daniel,
The mail in kits is what gives this such great flexibility. Perhaps a team doing the same yet giving away kits for free and with strategies to avoid Hawthorne effect will springboard this effort. Because, after all Academia is not a Corporation, yet.

The ongoing attempt by governments and pro-government activists to exert control over individual access to our genomes may make mail order *anything* very difficult to do in the future.

Moreover, anyone who reads this article (http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.10009…) must be struck by the level of bureaucracy built into the editorial and academic process. Drs. Greg Gibson and Gregory Copenhaver have inadvertently shined a spotlight on the realities of academic politics.

One notes immediately the aspersions cast upon the ethics of the eeeevul megacorp:

In this case, concerns were raised that a commercial IRB, paid for their opinion by the company, is not in a position of independence, but this is standard practice in the pharmaceutical and biotechnical industries, and similar concerns can be raised over the independence of University boards considering multi-millionâdollar studies

One is amazed that the similar concerns were even acknowledged in a piece like this, grudging though the acknowledgment may be.

the public good of disseminating valuable science performed by commercial entities

Note the implicit contrast in those words! Of course valuable science is not usually performed by commercial entities. Only a fool would think that Intel might be pushing the boundaries of semiconductor physics, Google advancing machine learning, or Roche innovating in synthetic chemistry.

Those corporate plutocrats are only publishing things that would advance their business and make a profit. You know, profit -- selling something for more than it costs you to make it. That's wrong of course. After all, if Intel is charging Joe $100 for a processor that costs them $10 to make, it must be wrong because Joe could have made that same processor in my backyard for $9!

(That's the deep comparative advantage argument for profit, by the way, folks.)

Unlike corporations, academics are pure of heart. They would never publish something that advanced their career. They would never rubbish a competitor's paper out of spite and never share confidential papers before review. They would never abuse their graduate students or suppress politically inconvenient research.

[end sarcasm]

The PLoS journals are unfortunately the worst in terms of this kind of self-important anti-commercial attitude. Academics are assumed to be above reproach and businesses are guilty until proven innocent. The problem with PLoS in particular is that they confuse their competitors (the for-profit journals) with for-profit entities *in general* and assume them to be evil.

This is going to leave them very vulnerable to a journal which is to PLoS what "open source" is to "free software" -- taking the good aspects of the openness model without the anti-business baggage.

The editors of PLoS Genetics recognize that the decision to publish this study, without IRB review as human subjects research and with some concerns over the consent document, and the fact that there is limited access to the raw data, will not sit well with some, perhaps many, readers.

What a JOKE. How many papers are published in PLoS that include the raw data? You can bet right now without looking that 80% or more of the articles published in the last month of the PLoS journals do not make all the code and data available. In fact, you can bet that Gibson and Copenhaver have not made all their published data available.

@Tina Turner you make some good points. The commercial conflict of interest exists of course and should not be ignored. However ALL authors have a conflict of interest, academics especially so in this era of having to publish vast quantities of papers to get grants, tenure, promotion, or whatever. History shows that most scientific fraud has been conducted by academics. The days of academia vs. industry as two opposite poles where traffic was one-way from the first to the second are over, they really finished in the 1980's

It's all about statistical power.

All of the "unfulfilled promise" of the Human Genome Project (should we have spent that few billion on wars instead?) will be fulfilled as we get more and more statistical power.

It's like a person looking at a 50s era computer calculating 435*786 and saying, "I could do that with paper and pencil!"

Some people just like to be sticks in the mud.

Another good news for GWAS:

The study used a restricted cohort of people adjudged to be Northern or Western European.

So the findings are really only applicable to those people, and not really of much use to anyone else.

One of my criticisms of 23andMe has been its bias towards European (Americans) of North or Western European origins. In other words, SW, SE Europeans, Middle Easterners, South Asians, SE and NE Asians, Australian Aborigines, Amerindians, Pacific Islanders need not apply, go elsewhere as you are not wanted. WASPs only.

Ponto... you are incorrect. If anything they are not bias towards Europeans. I came up as being ~10% Asian and their results have been more in line with the America Indians than with Europeans (the reasons are complicated). Minus this, I actually agree with the approach to race selection. If a gene is found in 80% of Europeans and 20% of Asians, they'll associate that gene with Europe, where other companies will say you're 80% European and 20% Asian. Their analysis isn't perfect, but ancestry is not an exact science.

Somehow I just can't care about this. Genomics is moving into a post-GWAS world -- or at least a post-common-SNP-GWAS world, because those are proving to have very little predictive power, and are useful mostly for preliminary pathway highlighting.

Until they're using far more high-res scanning than is now commercially feasible, this feels like getting excited about a circa-1996 StarTAC when everyone's getting an iPhone.

Hi Brandon,

Well, there's still things that can be done with GWAS data. For instance, I suspect we'll see some use of imputation (using reference data from sequenced individual to infer genotypes at untyped positions in people's genomic data) - this is by no means perfect, but it will add a little extra predictive power.

But yeah, the future is sequencing. But that won't invalidate 23andMe's model: they've collected phenotype data from a group of fairly engaged research participants who will be first in line when they launch their sequencing product, and that will start to provide some seriously powerful research fodder.

That's assuming the FDA actually lets them launch a sequencing product, of course...

Sample swaps at 23andMe: a cautionary tale

dgmacarthur — Mon, 07 Jun 2010 04:00:00 +0000

Sample swaps at 23andMe: a cautionary tale

Personal genomics company 23andMe has revealed that a lab mix-up resulted in as many as 96 customers receiving the wrong data. If you have a 23andMe account you can see the formal announcement of the problem here, and I've pasted the full text at the end of this post.

It appears that a single 96-well plate of customer DNA was affected by the mix-up. This resulted in incorrect results being sent to customers, with alarming consequences in some cases; one mother posted on the 23andMe community about her distress upon discovering that her son's results were incompatible with the rest of the family:

Still upset I checked family inheritance and noticed my daughter shared with me, and then I checked my son's. He was not a match for any of us. I checked his haplogroup's and they were different from ours. I started screaming. A month before my son was born two local hospitals had baby switches. I panicked and I checked over and over. My kid's were sitting at the computer because we all wanted to see the results. My son laughed but he looked upset. I called my sister in tears.

Although 23andMe's announcement of the problem is commendably open, and it appears that the problem has now been fully resolved for the customers involved, there are numerous complaints in the announcement's comments thread about the length of time it took for customers to get feedback on their puzzling data. In addition, there's concern about the company's failure to perform even basic error-checking (e.g. confirming that the sex determined from genetic data was consistent with that specified by customers), and its vagueness regarding the corrective measures it plans to take to prevent this from happening in the future.

This isn't the first time that personal genomics companies have mishandled customer data. In August last year, New Scientist's Peter Aldhous revealed sporadic problems with his mitochondrial DNA profile in deCODEme (which later turned out to be the product of a software glitch), and deCODEme also fumbled the process of translating 23andMe data last December.

Mistakes happen - as any lab tech can testify, these sorts of sample swaps happen with frightening regularity even in clinical diagnostics labs. However, if the industry is to survive the massive scrutiny currently being pointed in its direction following the Pathway/Walgreen's debacle it must avoid any appearance of being amateurish; this type of mistake adds even more fuel to the regulatory fire burning under the industry. 23andMe needs to move fast to make sure that serious safeguards are put in place to make sure this never happens again. In addition to increasing lab quality assurance (at 23andMe's testing facility, LabCorp) 23andMe should introduce basic sanity-checking procedures to look for obvious data swap problems.

Customers also have a role to play here in checking their own data for obvious mistakes - and it is noteworthy that in this case the sample problems seem to have been detected by customers rather than the company. This is a good time to repeat my advice from last year:

However, this incident serves as a canary in the personal genomics coal-mine - a warning of the challenges that lie ahead for companies in ensuring that massive, complex genetic data-sets are presented accurately to consumers.
It's also a useful reminder to personal genomics consumers to not take their results for granted. The process between spitting into a cup and viewing your genetic results online involves multiple steps where things can go wrong, ranging from errors in sample tracking (the most pernicious and difficult to correct), through genotyping problems (usually much easier to spot), to errors in data analysis and display.

In general the odds of a given genetic data-point being wrong are very low, but they're sufficiently far above zero to warrant caution in making too much out of any single result - mind you, given the extremely small effect sizes of most of the variants currently assayed by personal genomics companies, that's good advice anyway. Certainly it would be a good idea for customers to seek independent validation of any result if they intend to use it to guide serious health or lifestyle decisions.

But the most important piece of advice for personal genomics customers is to engage with your data. Aldhous only detected these anomalies because he was exploring his own genetic data in multiple ways, cross-checking it against both other data and his own (informed) expectations, and was persistent enough to follow up on the strange results he found.

That's a good example for other personal genomics customers to follow: rather than being a passive recipient of genetic forecasts, dig into your data and see if it makes sense, and keep asking questions until it does. In addition to making it more likely that you'll pick up any errors in your results, you'll also develop a much deeper understanding both of the nature of genetics and of your own genome.

Some errors you won't be able to spot, but make sure you're informed enough to spot at least the most glaring problems.

Here's the full announcement from 23andMe:

We recently determined that a number of new 23andMe customer samples were incorrectly processed by our contracted lab. We want to clarify what happened with the sample errors, how it happened and what we're doing to prevent it from happening again. Providing each and every one of our customers with accurate data is 23andMe's number one priority, and we fully realize the gravity of this incident.
Up to 96 customers may have received and viewed data that was not their own. Upon learning of the mix-ups, we immediately identified all customers potentially affected, notified them of the problem and removed the data from their accounts. The lab is now concurrently conducting an investigation and re-processing the samples of the affected customers and their accurate results will be posted early next week. We expect the investigation will be complete over the next several days and we will provide further details when we have them.

We are currently putting additional procedures in place that will add an extra layer of safeguards to help assure that similar incidents do not occur in the future. We are deliberating on a process that would include removing manual steps at the lab, completely automating the sample analyses, and implementing further checks of the data before it gets loaded into customer accounts. Please be assured that our testing laboratory's processes comply with strict professional, regulatory, and corporate quality assurance standards for ensuring that all laboratory test results are accurate. The laboratory will adopt corrective action as warranted based on the findings of the investigation.

The science behind 23andMe's personal genetics service remains proven and sound. We recognize that this is a very serious issue and your trust is of the utmost importance. We hope that this helps clarify what has happened and what we are doing to prevent these problems in the future. Please contact me at khomenko@23andme.com if you have any further questions. We appreciate your comments and feedback.

Update 8/6/10: 23andMe has provided details of the cause of the incident and the steps it has taken to prevent similar problems in the future.

dgmacarthur Mon, 06/07/2010 - 00:00

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decodeme

errors

http://www.nature.com/news/2010/100602/full/465537a.html?s=news

Oh dear. As you say, it's a mistake that can, and probably has, happened to every lab. I wonder what happened, 96-well plate inverted? Or was it the data transfer where there was a mix up. Like you though, I am amazed that such a gross error was not picked up in their QC - basic procedures should have detected it, including blind controls (do they run them?) and the gender determination you mention. These are the sort of protocols that CLIA is supposed to control for.

Anyway - it's a biggish error but I hope we don't see any gloating or self-satisfied comments from competitors, would be a bad move, because one day it will happen to them as well.

Please be assured that our testing laboratory's processes comply with strict professional, regulatory, and corporate quality assurance standards for ensuring that all laboratory test results are accurate.

I don't find that very reassuring, somehow ...

Nature News has a timely piece this week:

Alla Katsnelson (2010)
Biologists tackle cells' identity crisis:
DNA fingerprinting scheme aims to make sure researchers are working on the right cells.
Nature 465, 537 | doi:10.1038/465537a

I am one of those who received the mixed-up results from 23 & Me, and also one of the ones who caught it early because I stay on top of the DNA lines I research. First of all, we all KNOW lab mix-ups happen. I have had that happen in a doctor's office where the doctor insisted the medical results were correct. I went to the lab and got a retest which proved they were wrong. Secondly, the company reacted within a 24 hour period. Yes, I was initially shocked and upset, when I received the results. I also knew they had to be wrong. I contacted others on the ISOGG (Int'l Society of Genetic Genealogists) mailing list to find out who else got bad results. I also monitored the 23 & Me Community Forum and also found others. Many of us worked together to contact those we knew at 23 & Me to find out what the problem was. Later we were sent messages explaining there was a problem and the bad results were pulled. Some of us received phone calls to discuss it with 23 & Me as well, and asked if we had any questions. I worked many years for big corporations and know that that type of response in 24 hours was great. It is sad that this happened during all the furor over regulating this market. Sadly, it was California's government regulation that forces 23 & Me to outsource their lab work. I definitely hope nothing like this happens again, however I also want it recognized that this company took responsibility early to resolve it. I lived it and am satisfied with the response!

Good comments Nora, and you're quite right, the worst timing possible.

Still, better than cutting off the wrong leg or removing the healthy kidney...I don't think that 23andme need to consult BP PR damage limitation just yet (although probably they are the last people to call on for help)

One of my family member's test was also affected by this mix-up. Since I am the genetic genealogist in the family, I quickly realized that there was a mistake in the reporting and contacted 23andme. For me, personally, the response from 23andme was immediate and satisfying. In this case, the community worked together to quickly ascertain that there was a problem and to alert those who may have been affected. This was an important step toward self-regulation. Now we must quickly take the next step toward ongoing, qualified and organized self-regulation. This way, in my opinion, the genetic genealogy community will demonstrate that there is not a need for regulation from outside agencies.

I can't defend sloppy work like this, and I can't imagine an acceptable excuse for a corporate culture that supposedly prizes informatics and superior operational efficiency like 23andMe purports to do. But, in perspective, I remember than the United States Veterans Hospital had recently disclosed that veteran patient records had been scrambled. The story was told to me that the scramble was discovered when a female patient complained about her prescription for erectile dysfunction drugs.

I doubt that the US VA mixed its records due to insufficient federal regulation and oversight. I would like to mention this before anybody suggests that the solution to incompetence is to declare incompetence to be illegal.

Disclosure: I have a consulting arrangement with 23andMe, acting as a liaison to the genetic genealogy community. However, I have no insider knowledge about the mechanics of database management, and the observations here are mine, not official policy of 23andMe.

The batch in question was uploaded Tuesday night. I happened to be up in the middle of the night, and I had received several queries about odd results. I immediately notified 23andMe, doubtless along with others who wrote to 23andMe directly. I received a response before 7:00am Wednesday that they would look into the matter. Over the course of a single day, they identified the scope of the problem (just one of several 96-well batches uploaded that night) and notified everyone who was affected. I find that to be an admirably prompt response, given the complexity of the analysis.

I'm not altogether certain that a "sanity check" such as gender would be practical. The lab has only a bar code, which somehow got out of sync with the samples in this particular batch. 23andMe later connects the bar code to a claim code, which assures that the testing laboratory has no way of identifying an individual. There may be no personal information attached to the claim code, since the person who orders the test may not have created a website account with the claim code, or may not even be the person submitting the sample. The best sanity checks (I'm proud to say) came from the genetic genealogy community, which not only "engages with the data" but has a very collaborative approach to studying it.

Ann Turner, M.D.
co-author (with Megan Smolenyak) of "Trace Your Roots with DNA"

Sounds like they did a very commendable job recognizing the error and communicating information. Simple mistake, and its absurd to think mistakes never happen. (its not like they were repeatedly fined for safety violations long before the rig blew up, or anything like that - we should save our outrage for the corps who deserve it)

I was thrilled when 23andme offered the test for such a HUGE discount on DNA day awhile ago, but I did wonder if they had the infrastructure to keep up with the one day demand spike. I've not yet submitted my test, figuring I'd give them a bit of time to work through the early returners.

I think now is the perfect time to send back my kit, I'm sure they are going to be extra careful from here on out.

@Ann

Thanks for your inside information. It does seem like 23andme reacted quickly. I understand about the problems with using gender testing as a control but you absolutely cannot rely on the "best sanity checks (I'm proud to say) came from the genetic genealogy community". It's not a sanity check, it's a discovery of wrong results already distributed. Running control DNA samples, several per 96-well plate, would have picked up the error if it had been a total scrambling of the data, or the results being out of sync. I've been through these sorts of errors several times over the years, but they were caught before any damage was done. Running loads of controls (rather than just 1 or 2 per complete run) is expensive - but worth it in the long run.

@Ann:

I'm not altogether certain that a "sanity check" such as gender would be practical. The lab has only a bar code, which somehow got out of sync with the samples in this particular batch. 23andMe later connects the bar code to a claim code, which assures that the testing laboratory has no way of identifying an individual. There may be no personal information attached to the claim code, since the person who orders the test may not have created a website account with the claim code, or may not even be the person submitting the sample.

And I thought consent was required!

Anyhow, to assume there are no errors, and not check what you can check, for whatever reasons, is just complacent ...

@ Keith

Running control DNA samples, several per 96-well plate, would have picked up the error if it had been a total scrambling of the data, or the results being out of sync. I've been through these sorts of errors several times over the years, but they were caught before any damage was done. Running loads of controls (rather than just 1 or 2 per complete run) is expensive - but worth it in the long run.

... and I don't think loads of controls are necessarily the answer.

Now, I have submitted sample manifests to both Affymetrix and Illumina for academic GWAS, and led subsequent sample reconciliation efforts.

We were expected to supply 3 types of information as part of the sample manifest in addition to an anonymous sample identifier:

1. the subject's sex, at the vendors' request and expressly for sanity checking each group of samples, as well as singly;

2. DNA extraction parameters (concentration, method) in case these relate to poor performance, for which we will be billed;

3. whether the sample in well x is an intentional duplicate of a sample in well y.

The latter is probably the most open to negotiation, but "none" has not been an option, as far as the vendors are concerned.

With regards minimising the number of non-billable samples, one could use one or two reference samples per 96-well DNA plate as positive controls, and TE buffer as a negative control, but this would only tell you about day-to-day processing efficiency, and genotype repeat rates in near-perfect samples.

By preference, and where we have the DNA stocks, we have included a different pair of study samples in each plate, in different well positions (so we can detect plate rotations), and in different rows and columns (as the processing is not usually plate-based, but in groups of rows or columns, and this helps detect processing issues).

Yes, I agree this is much harder to automate than sticking positive and negative controls at each corner of a plate, but you do find out rather more. For instance, that even the very best labs make mistakes.

Errors like this at a CLIA-certified laboratory make me wonder about the prevalence of similar errors in the medical arena, with potentially even worse consequences. Errors in DNA microarray results, like those provided by 23andMe, can be relatively easy to identify, compared with, for example, blood test results or drug test results. (For example, earlier this year, I received anomalous blood test results from Quest Diagnostics, and I suspected the possibility of laboratory error, such as sample swap; however, I have no easy way of proving or disproving the occurrence of such an error.) Doctors can base life-and-death decisions on the results of a blood test and a false positive drug test result can have obvious negative consequences, so I think this could be a serious issue even outside the area of genetics testing.

Thank you Neil for more clarity and detail - I agree with the controls you propose. By "loads of controls" if I had added detail I would have said what we do: standard DNA samples and negatives plus several "customer" sample controls which as far as the lab is concerned (either internal or outsourced) are genuine samples, so these are added randomly to the plate (2 or 3 per plate).

I suppose for DTC it's hard to ask for too much info, even sex, when promising absolute confidentiality. For academic GWAS it's OK, there is a relationship with one customer for 1,000's samples rather than 1'000's of relationships, one per sample.

There's no reason not to have an "opt-in" questionnaire when people register on the website (after mailing off their sample) for the purposes of sample tracking: sex, eye colour and hair colour alone would be a start. If even 50% of customers filled in these details that would be enough to spot a dodgy plate with high confidence, even allowing wiggle room for incorrect answers given by some customers. Add the plate-specific control samples proposed above by Neil and you have a very good system for preventing plate mix-ups.

In fact, it's entirely possible that enough customers already provide these details prior to sample-handling in 23andMe's optional phenotype surveys for this type of analysis to be done.

Another perspective: we're suggesting human biochemical medical laboratory procedure as third party laypeople in a blog comment thread.

Thanks Keith.

I suppose for DTC it's hard to ask for too much info, even sex, when promising absolute confidentiality.

Yes, and I can also see that it would be problematic for a DTC company to say:

if you give us some not-very-personal details we are more confident we'll give you back the correct data

Less cynically, the best lab test we have for sample continuity is concordance testing against results achieved independently from the same sample, but handled differently.

This could be done (where blood is taken) using a bloodspot/Guthrie card and genotyping a few very common SNPs - as although it takes quite a few SNPs to make a sample unique, it doesn't take many to show up a problem, as the lab has to make a (hopefully very rare) sample handling error and the samples still have to match afterwards.

Not sure if something similar can be done splitting a saliva sample?

Or perhaps the data should come with a health warning? To take Daniel's examples above:

you've taken our test, so you're probably the sort of person who thinks genotypes are predictive. So, from your data, we PREDICT you are probably a brown-eyed male with curly hair - if this is not you, please contact your customer representative ...

PS: Andrew - if you want a reference for this, search for "we excluded 16 samples".

I had an electrician working on my house when he discovered through genetic testing that his two year old daughter wasn't his. He lost his mind and gave all my electrical devices 220 instead of 110 volts. It fried all my clocks and I knew something was wrong when my refrigerator sounded like it was a race car. I got a new electrician and left the old one alone even though he had cost me a lot of money. A funny story now, to me, but you can imagine the human tragedy of parents and children feeling betrayed and disconected from each other.

Another perspective: we're suggesting human biochemical medical laboratory procedure as third party laypeople in a blog comment thread.

Neil Walker is no layperson when it comes to large-scale sample handling.

As per a recent Spittoon blog post, future customers will be asked about their gender when submitting the sample.

http://spittoon.23andme.com/2010/06/08/update-from-23andme/

Thanks Ann - I've added my comments on the 23andMe response here.

Did the search, for other readers:

http://www.nature.com/nature/journal/v447/n7145/full/nature05911.html#a…

"We excluded 16 samples with discrepancies between WTCCC information and external identifying information (such as genotypes from another experiment, blood type or incorrect disease status)."

As for my comment, I don't mean to say that these suggestions are not good or not relevant. I thought that the idea to keep samples and results orthogonal was a credible solution. I don't know how or why that didn't work in practice because I don't know what happened. The public story is that a plate was flipped. So, I think that the problem was with the lab equipment that didn't differentiate between flipped plates, not that the theory of keeping data and samples orthogonal was proven to be fundamentally flawed in theory. That may not be the fault of 23andMe at all, although they would still be liable as providers of the test results. I don't know.

I find it disturbing that there were no controls in the plate. ALL the wells were customer samples? That makes no sense to me. I've never worked anywhere that didn't include at least one negative control (TE or similar) and one known/positive control well in order to catch these problems and to provide data QC. And that's including always labelling or barcoding plates on the same side every time to prevent mis-loading plates.

Well, for better or for worse, I was personally uncomfortable with having identifying information (gender, etc.) precede my obtaining results from 23andMe. This is for all of the reasons that Daniel mentions in the above post, where he references back to his 2009 post. As I informed the med students in my Personalized Medicine class, my greatest fear upon being genotyped was spending $$$ and ending up with the genotype of some âunknown 23andMe custodianâ (through a mix-up, as just occurred). In fact, I was so suspicious of the overall process of genotyping that I felt it mandatory to be genotyped by at least TWO different DTC providers; 3 would have been preferable, so that at least two sets of data should agree and simultaneously comply with my personal traits (gender, blood type, etc.). Fortunately, Navigenics had a deal last year at 80% off list price for joining the Scripps Genomic Initiative (Eric Topolâs). Only upon considerable scrutiny of the data from both 23andMe and Navigenics was I convinced that I was actually looking at my own genetic data and not that of some âunknown DTC custodianâ. Thatâs particularly relevant, given that Navigenics provides APOE results. At any rate, given the number of possible steps over which an error can arise, it amazes me that the process works as well as it does. I think 23andMe did a pretty good job of resolving the problem, and I think that paying attention to the wise advice on posts like this (and I believe they do) provides free support for the DTC genetic companies.

Bottom line- Iâm UNCOMFORTABLE providing pre-identifying information; the less the better. I think the system worked itself out. I realize most people canât afford a single DTC genetic test, let alone two. Just my opinion.

"basic procedures should have detected it, including blind controls (do they run them?"

Quite possibly blind controls were carried out yet showed nothing wrong.
Say we take 10 samples out of the 96 for a sanity check (that's over 10%) but for whatever reason those 10 were the only 10 not affected by some error (say the random sampler caused all 10 to be taken from one specific area of the sample tray, where the error was confined to another area of the try, could happen).

The only way to avoid this is to have all samples retested by another facility using different procedures altogether, compare the results, and have everything tested again at a 3rd independent facility with different procedures from either in case any differences are found.
Even then there's a miniscule chance things turn out the same in all tests even though they are in error, but it would reduce that chance as much as possible.
The cost for doing so would however be horrendous, effectively trippling the processing cost of each sample (as well as requiring larger sample sizes of course, as each sample must be sliced in at least 2 more parts than at the moment).

I do not and cannot know the testing procedures in place, but can speculate that there was some sanity checking and in this case due to whatever reason it failed.
Either the sample set was abnormally homogeneous for all the criteria used in the sanity check (maybe an entire run for a sorority of blue eyed black women who are natural blondes and the sanity check tests for gender, eye colour and hair colour just to give an extreme sample?), or the sanity check was performed on a sample of the total batch and nothing wrong was found in that sample (which might indicate a problem in the sampling procedures at best).

The problem was a flip of the whole plate, so even one known control in a known position anywhere on the plate would have revealed it in this case.

Obviously it's true that no amount of safeguards will protect against all possible calamities, but it's possible to minimise the risks of massive failure and common sources of error using some straightforward (and reasonably cheap) measures.

@23

my guess - and it is only a guess based on what we have been offered as a starting layout by the larger vendors - is that:

[a] a lab technician has been tasked with putting prepared samples into a 96-well plate, leaving specified wells empty for controls;

[b] this job has been done at a bench, by hand;

[c] the control samples are added in a separate step prior to automated processing on a robot.

Now, plates are usually manufactured to be hard to insert into a robot incorrectly - some have a corner nicked off, some have indentations on one side only (to assist a plate grabber) and most have barcodes on at most one long and one short side only so they can't be scanned in the wrong orientation - but, as they are only about 4" by 3", it is still possible to get it wrong on the bench.

One failure mode that is possible whilst using controls (and I'd assume their use is a given in a CLIA-approved lab) is to place them with rotational symmetry - typically the first and last wells are used - and to have the controls added in a separate process to the test samples.

All idle speculation of course.

@23

The only way to avoid this is to have all samples retested by another facility using different procedures altogether, compare the results, and have everything tested again at a 3rd independent facility with different procedures from either in case any differences are found.

Under the scenario I suggest above, a retest of the same plate would give the same result?

To be sure, if these results were being used to arrange a kidney transplant on the basis of tissue typing, or other major medical intervention - and Illumina, at least, are moving into this market - I would expect a complete retest of an independent sample to confirm that no sample mixups had occurred.

I don't think the same standards are not intended to apply here, and costs reflect this.

I think i have 1 that tops that,,, I had a DNA/Paternity Test REVERSED after 5 years by the Medical College of Virginia. In '03 the test came back "Negative" but when they "re-ran" the same sample 5 years later, the test came back "POSITIVE". MCV did, however, apologize if this caused any "inconvenience"........

" but, as they are only about 4" by 3", it is still possible to get it wrong on the bench."

Which suggests a similar system to prevent incorrect orientation be installed on the bench.
Engineering solution to a human problem :)

Especially if the placement is mechanically impossible if incorrectly oriented, this shouldn't be too hard to implement.

There was a case a few years ago in the UK where the owner of a paternity testing company took the money, threw away the samples and made up the results - http://bit.ly/bnv0xc

I like Dan Vorhaus' argument abouth this being a reason to favour DTC...at least he makes very good points showing why it cannot be used as anargument against DTC - http://bit.ly/cU8A2Q

As one with a Chemistry background and some experience in analytical research, relying on only lab and one test result is risky.

When I had my Y-DNA tested some years ago, I used both Family Tree DNA and Relative Genetics.

Markers tested by both companies were found have the same value, and the reliability of the methodology was was confirmed.

After reading this article, if I do additional testing, I will continue to do duplicate samples at two different laboratories.

When I found out that I was surprisingly related to the McGuire clan and not to listed Fox DNA profiles, I could believe that linkage.

If it is worth doing, it's worth the extra cost to establish the validity of the data.

"Sadly, it was California's government regulation that forces 23 & Me to outsource their lab work."

I'm not quite sure what this comment means. The lab that does their wet work is CLIA certified, and if it is in CA that means the people doing the pipetting were licensed clinical lab scientists. They contract their work out (I am supposing so that it is cheaper than setting up a CLIA facility de novo) -- would they not have performed periodic vendor audits so that they could keep an eye out for performance improvement opportunities. The CA licensure situation is a pain, yes, but I don't think THAT has anything to do with them outsourcing. IF you are going to be testing human samples that have anything to do with turing results around that are used for diagnostic or prognostic purposes, it pretty clearly states in CLIA regulations that this has to be done at a CLIA certified facility by licensed scientists -- THIS is why 23&me got the cease & desist letter from the state a couple of years ago. CLIA regs also set a framework for QA/QC procedures, and this sort of sample integrity incident will be something that will be closely reviewed the next time the lab is inspected by CLIA inspectors. THIS is why 23 & me needs to have someone on their team that is from the clinical lab arena -- not just a bunch of data mingers.

Where to next for personal genomics?

dgmacarthur — Thu, 20 May 2010 18:35:00 +0000

Where to next for personal genomics?

The brief Golden Age of direct-to-consumer genetic testing - in which people could freely gain access to their own genetic information without a doctor's permission - may be about to draw to a close. In a dramatic week, announcements of investigations into direct-to-consumer genetic testing companies by both the FDA and the US Congress have sent the personal genomics industry into a spin, and it is still impossible to say exactly which way it will be pointing once the confusion passes.

I've been frustratingly unable to find the time to cover the developments as they happened due to other commitments - but fortunately they have been extremely ably covered elsewhere, notably by Dan Vorhaus over at Genomics Law Report and Kirell Lakhman at GenomeWeb.

Here's a high-level summary for those who haven't been following closely:

On May 11, direct-to-consumer genetic testing company Pathway Genomics announced that it would be partnering with drugstore chain Walgreens to offer its genetic testing kits on the shelves of Walgreens' 7,500 stores.
The same day, the director of the FDA's Office of In Vitro Diagnostic Device Evaluation and Safety, Alberto Gutierrez, was quoted as follows in the Washington Post:

"We think this would be an illegally marketed device if they proceed [...] They are making medical claims. We don't know whether the test works and whether patients are taking actions that could put them in jeopardy based on the test."
Two days after the Pathway announcement, and following a letter from the FDA to Pathway, both Walgreens and rival CVS Caremark, who had also apparently been planning to stock the kits, decided to drop the idea of offering Pathway's product in their stores.
Yesterday Dan Vorhaus broke the news of a newly-launched Congress investigation into direct-to-consumer genetic testing sparked off by the Pathway controversy (the announcement cites "recent reports that at least one of the companies is seeking to sell personal genetic testing kits in retail locations, despite concern from the scientific community regarding the accuracy of test results").

As always, the best place to go for detailed legal analysis of this ongoing furore is the Genomics Law Report, and in particular Dan's lengthy and incisive first response to Pathway's announcement, and his subsequent analysis of the FDA crackdown.

I have a few overall points to make here.

The end of direct-to-consumer disease genomics?

Nothing is certain yet, but it's entirely possible that these events mark the beginning of the end of DTC genetic testing for health-relevant traits.

The DTC personal genomics industry has so far enjoyed a bizarrely prolonged period of respite from the stifling regulatory embrace of the FDA and other regulatory bodies (while the technical validity of all of the major personal genomics companies is governed by the Clinical Laboratory Improvement Amendments of 1988, there's currently no regulation regarding the interpretation of the raw data).

It has always seemed inevitable that this period would end with a regulatory crackdown, although the precise nature of the eventual regulation - and the events that would trigger the regulatory hammer to come down - were impossible to foresee. Now the hammer is dropping, and although its aim seems capricious (see below), there's little doubt that its long-term impact will be massive. It's certainly not beyond the realms of possibility that companies will be forced to entirely discontinue DTC provision of information for any health-relevant trait.

Personal genomics companies are to some extent prepared for this eventuality. For instance, several of the major companies (e.g. Pathway and 23andMe) have split their disease risk predictions into a separate product from their more "recreational" offerings (such as ancestry, genealogy and non-disease traits), potentially allowing them to maintain a DTC revenue stream even if the DTC disease genomics angle was blocked. (Kudos to Dan Vorhaus for spotting the motives for this behaviour back in July last year.)

Today, GenomeWeb reports that at least one DTC company has gone even further and dropped its direct-to-consumer offering entirely. Navigenics could probably also drop its DTC offering without much harm to its sales, since the company has by all accounts been spectacularly unsuccessful in tapping the DTC market. We may well see the same approach taken by other personal genomics companies in an attempt to stave off the regulatory claws of the FDA.

This outcome would be an absolute tragedy for those of us interested in thoroughly exploring our own genomes. Anyone who has ever tried to get the raw data from their own medical tests from doctors will know how ludicrously difficult this is, due to a combination of bureaucratic incompetence and litigation-shy clinicians. Now imagine that difficulty, multiplied by the sheer scale of genome-level data and the near-complete ignorance of the vast majority of doctors about genetic information.

Comedic blunders from the FDA

While confusion reigns in the DTC genetic testing industry, this whole episode has revealed one thing very clearly indeed: absolute incompetence on the part of the FDA. One cannot help but shudder at the fact that such a transparently clueless agency wields so much power over so many industries.

In a great article over at GenomeWeb, Kirell Lakhman points to a series of contradictions in public statements made by the FDA over the last week (in what he refers to as a "seemingly uncoordinated and contradictory investigation").

Here is an agency that has sat back and watched the industry (albeit lazily, given that it was apparently unaware of Pathway's existence until the Walgreens announcement) for two years, giving no clear guidance regarding its regulatory intentions, and then suddenly announces that retail genetic testing is probably illegal via a quote in the Washington Post.

In addition, the motive for stomping specifically on Pathway seems entirely arbitrary. Gutierrez said in an interview with Pharmacogenomics Reporter (subscription only) that "The fact is that Pathway's bold move to make themselves noticed achieved its end and brought them to our attention", suggesting that the agency would have been happy to let DTC companies continue to operate if they'd done so more quietly.

It's a doubly bizarre statement given that the industry in general (and 23andMe in particular) has been conducting aggressive marketing campaigns to the wider public for a long time. Why did the Walgreen's campaign overstep the mark any further than, say, 23andMe's appearance on Oprah or its zeppelin campaign? It's impossible to know, especially in the complete absence of any substantive guidance from the FDA on what is or isn't acceptable behaviour.

Of course the power of the FDA is so massive, and so arbitrarily wielded (the technical term is "enforcement discretion"), that you won't be hearing many public complaints from personal genomics companies out of fear of retaliation. Instead, the industry is lining up to vow full compliance with the investigations from the FDA and Congress, like shop-keepers telling everyone who will listen how great a job the local gangsters are doing even while they fork out their protection money.

Do we need FDA regulation?

Regular readers will know that I think - for all its faults - the personal genomics industry provides a net benefit to society. Sure, the information provided by personal genomics tests currently has limited utility in terms of health prediction, at least for most of us; but by allowing people to engage with their own data, and generally doing a pretty good job of conveying the complexity and uncertainty of modern genetics, personal genomics companies are non-trivially increasing genetic awareness and literacy, an important public service as we enter the genomic era.

It's worth emphasising that the major personal genomics companies have done a fairly respectable job of self-regulation so far: 23andMe et al. generally present genetic risk information in a way that is far more accurate and accessible than anything we have seen (or are likely to see in the near future) from the medical profession.

It's also important to note that precisely zero evidence exists for the notion that genetic test results are likely to cause serious harm to consumers. So while Arthur Caplan may fret over the idea that customers assigned a low risk of heart disease might "go off and drink milkshakes all day", the existing sociological evidence suggests that genetic risk data alone has relatively little negative effect on consumer behaviour or mental health.

There certainly is room for regulation that filters out the bottom-feeders in the industry - but that is not necessarily a job best done by the FDA. As Dan Vorhaus points out, the Federal Trade Commission, as an agency focused on consumer protection, might be well-placed to step in. In addition, the recently-announced NIH genetic test registry - particularly if it is made mandatory - will hopefully serve as a valuable resource for consumers, allowing them to make informed decisions without requiring them to have an ill-informed clinician hold their hand while they do it.

By all means prosecute companies that make false claims of fact or provide poor-quality assays. By all means provide consumers with additional resources to allow them to make informed decisions. But don't create regulation that makes it hard for new companies to enter the space or introduce new technologies; and if people decide that they don't need their doctor to peer into their own DNA, let them make that choice.

Final thoughts

After years of speculation, the long-awaited crackdown has come. Exactly what type of industry will emerge from the other side is still completely unclear, and we can only hope that regulators restrain themselves from the heavy-handedness they have inflicted on other industries.

Personal genomics is a young field, but it's also a crucible for the future of personalised medicine. Excessive regulation at this stage will cripple innovation in the industry by raising the cost of starting new businesses and developing novel approaches. If the FDA is given free rein to stifle the field with formidable regulatory requirements this will do long-term damage to the development of personalised medicine.

I'd encourage US readers to make their thoughts on this known - write to your politicians, tell them what you've learned from your own genome, and inform them about what a terrible idea excessive regulation would be for the future of medicine.

dgmacarthur Thu, 05/20/2010 - 14:35

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Hi Daniel,

Thanks for the post. I'd also add that it's not merely an opinion that DTC genetic tests are not likely to cause serious harm to consumers.

In fact, two oft-cited peer-reviewed studies come to mind. One, published in the New England Journal of Medicine last year, had to do with the ApoE gene, which increases one's risk for developing Alzheimer's disease. The study showed that disclosing results of an ApoE genotyping test to adult children of patients with Alzheimer's "did not result in significant short-term psychological risks."
[http://content.nejm.org/cgi/content/short/361/3/245]

The other study, which was led by the National Human Genome Institute, showed that patients who use DTC genetic tests âmay be among the most motivated to take steps toward healthier lifestyles." This paper was published in 2008 in Genetics in Medicine, the journal of the American College of Medical Genetics.
[http://journals.lww.com/geneticsinmedicine/Abstract/publishahead/Charac…]

But somehow I doubt that even these peer-reviewed points will sway the FDA or Henry Waxman.

Kirell Lakhman

Daniel,
All this pity part crap is for the birds.

Personalized Medicine is Medicine Daniel. When you have companies restricting Terms of Service to Not be used for Medicine (in order to avoid responsibility and regulations), how can they be a part of Personalized Medicine?

1. A test for BRCA mutations is medicine, no matter what any terms of service say.

2. Playing medicine without a license is illegal, playing diagnostic lab and selling your wares without CLIA approval is stupid, Which is why Pathway started with CLIA and 23andME and Navigenics ran out to get it PDQ.

3. This is a case of too deep into medicine without any clue how to do medicine.

I had said this for the last 3 years now. Personal Genomics will continue to exist, just not in the fashion which free wheeling sans regulation spit partiers wish to have it.

Is that a bad thing? Is it so bad to say "Slow Down, let's look at what we are doing? Is it the best way to proceed?"

I don't think so. My ex partner and I went down this logic exercise in 2005 and came up with one conclusion

Physicians who know what they are doing NEED to be involved to pick up the pieces and help people understand.

Does a research PhD geneticist need help from a physician? Well, I think the Quake paper indicates, yes a clinician would have helped. At least to get the right studies to evaluate risk.....Not just analyze a genome.

-Steve

Awesome post, Daniel!

Unfortunately, Steve must have missed your point about "the near-complete ignorance of the vast majority of doctors about genetic information"; this is a big bottleneck to the path he is suggesting. In 2010, most American doctors don't even speak about genetics, let alone understand what a DTC genetic test is for or how the results might be interpreted. For that, we'll have to wait for the next generation of trained physicians, starting with the Path residents at Beth Israel Deaconess. Figure a decade before that trickles down to doctors setting up shop in Syracuse, NY. Who wants to wait that long to get their personal genome report?

-Bob

It is my genetic information it should be available to me without interference from the government or anyone else.

If I want I will consult a physician or other expert for help in interpreting and understanding but I should not in any event be denied access to information that is my very essence. To do so is dictatorial.

I have tested with 23andme and I have asked both my primary care physician and three specialists that I see to review my results with me and they have no interest in doing so. So much for professional help in interpreting my data.

Given the bureaucracy of the insurance companies and the reluctance of any physician to release any type of raw data to a patient if these test become medical procedures you will never see you raw data. Modern physicians guard this sort of information â raw data - as jealously as the Catholic church guarded theological matters pre-reformation and for the same reasons â control, period.

I find the increasing amount of control over what I think and do and what information I have access to by the government and professional groups to be alarming.

Andres Bolinaga

I think that the reports of the death of DTC genetic testing industry are greatly exaggerated. The highest regulatory burden the FDA could possibly impose on DTC genetic test kits is to make them Class II medical devices. This would place them in the same category as pregnancy test kits, and such kits are obviously attainable from the local drugstore. Sure, the DTC genetic testing industry might be better off under the current Laboratory-Developed Test (LDT) regulatory regime; however, a Class II designation will hardly decimate the industry.

@Matthew Markus: While I agree that DTC tests would be unlikely to be considered Class III devices, the "highest regulatory burden the FDA could possibly impose" would be to not approve the tests at all, at least in their current form.

Requiring these products to receive FDA approval (Class I or Class III), but to lose the DTC in order to receive that approval, would do considerable harm to the industry. I'm not sure it would decimate DTC genetic testing under the colloquial meaning of that word, but it would certainly do so under the technical meaning. I think that's one of the many points that Daniel makes above.

I agree, however, that developments to date do not necessarily herald the death of DTC. The reality is that we do not yet know what regulatory action the FDA (or Congress) will take, if any. Remember, DTC went through a round of warning letters and fear of over-regulation once before, and removed relatively unscathed.

@Dan Vorhaus: Thank-you for providing a true worst-case scenario. Perhaps I was too bold in my previous statements. My confidence, though, stems from the availability of kits like this:

I cannot see the FDA getting into the business of judging what information is too frightening or important for a person to know. I firmly believe that the agency is only interested in making sure that DTC genetic test kits face the same scrutiny as other publicly available test kits. Thus, I would be shocked if the FDA acted in a manner that installed physicians as gatekeepers to genetic information.

"This outcome would be an absolute tragedy for those of us interested in thoroughly exploring our own genomes. Anyone who has ever tried to get the raw data from their own medical tests from doctors will know how ludicrously difficult this is..."

About 15 years ago in London I went to my GP. Reception hands me my medical notes on the way to the waiting room. This was a departure, normally medical notes were given straight to the doctor. So I took the opportunity to sneak a look my records, reception sees me, tells me off saying I'm not allowed to look at them...that was the extent of NHS paternalism which should be gone forever.

I hope that the FDA have a well thought out plan for what they are doing and that it's not the case that they were just bounced into an unplanned action by media pressure. They have had long enough. I hope that they will review any evidence of benefits vs. evidence of harm that has occurred over the last few years. Will they listen to customers as well as academics, medics and self-styled authorities on "consumer protection"? It would be great to have personalised medicine for all through medics - if only there were anywhere near enough of them able and willing to provide it.

I hope that they will also look at the consequences of strict control on health information via DTC companies. If it is prohibited (as in Germany) DTC will probably not go away. I don't suppose they will prohibit the non-health related services, I will still be able to get my gene-scan. This could lead to a new generation of "bottom feeders" providing completely unregulated online health interpretation services delivered via servers from any convenient country in the world. DeCode did this for 23andme customers for free, obviously DeCode are not bottom feeders - the point is that it is relatively easy and inexpensive to set up the service, what is difficult and costly is providing a serious service.

At least with the current situation we have a few high profile companies that are under massive scrutiny, keeping them honest and on there toes. None of them are offering magic weight loss or IQ predictions. If a consumer wants to get some relatively bland gene related medical information he/she knows who to go to.

Maybe the current system of "regulation" that has evolved is not too far from the optimum, maybe it just needs a bit of tweaking.

Not all regulation is misregulation. While I agree it would be a shame if heavy-handed interference from the FDA (or Congress) ended the availability of DTC genetic testing, it doesn't seem like that verdict has been written yet. I would think it would be a net win if some sensible regulation on the industry were established so that (a) reasonable providers could cite their bona fides and (b) dodgier companies could be flushed out.

I fully agree with the point that medical professionals are abjectly unprepared to help patients make sense of these data, but that's a whole different problem...

I love how people who are not physicians and some who are not even research geneticists are here to pronounce how horribly not ready physicians are for handling genetic data. While I as a physician who teaches genetics to Yale residents knows that they aren't ready for the intricacies of some things, they know more about genetics than the average Joe who would buy a test at Walgreens or on Amazon.

That is the silliest argument I have heard. What makes Comp Sci 403 know more biology than a physician? It doesn't. What makes anyone at all know more biology, other than PhD level geneticists? Answer most people don't.

Is a bottleneck that destructive a thing right now? No, the money has already been invested in these companies, they won't fold, they will just find another way to sell tests. My guess is a non-medical and a medical version.....Or just straight sequence with no medical interpretation.

Why would you super smart people need that interpretation anyways?

Steve

Steve,

You don't have to be a clinician to know how woefully under-prepared the medical establishment is for genetic information. All you have to do is take your 23andMe or Counsyl profile to your doctor and see how they respond. The vast majority of doctors have no understanding of - and worse, no interest in - genetics.

Let me ask you a question outright: let's say I did get my genome sequenced tomorrow, and had it sitting right there on a portable hard drive. Who would give me the best explanation of its medical relevance: my GP, or 23andMe?

* A 510k app requirement would destroy the industry as currently constituted because it cannot meet the diagnostic standard for GWAS associations. The FDA is a (much) higher bar than Nature or even NEJM.

* It is important to realize the gravity of this situation. A cavity check on DTC genetics companies in public view is not going to be pretty. It will spread to reduce public confidence in ALL genetics. Ultimately this will drive things overseas. Obama on genetics = Bush on
stem cells.

* ASHG is foolishly on the warpath about ancestry too, so I wouldn't count on that as a bolthole.

DTC cos need to use some of those millions and political connections to get this thing halted right away. If they don't fight back with clever political protests they are toast. Get 1000 people to protest in front of Waxman's office snuffing out candles titled "genetic privacy" and "American innovation". Go for the theater and hit back hard. If you admit to wrongdoing it's over, at that point the vultures descend.

This is all happening by the way because of 23's layoffs. Really dumb move. When they were the strong horse they were untouchable. As their aura evaporated they went from invention of the year to an f'ing congressional investigation in 18 months. Sergey needs to brush Anne aside and take the wheel again if there is to be a chance of survival.

@Daniel,

1. "It doesn't take a clinician to know...."
Have you presented your data to your GP? I review these tests all the time. I also teach other doctors how to.

2. "The vast majority of doctors have no understanding of - and worse, no interest in - genetics."
Daniel, should they have an interest? Having an interests assumes there is something important there. In some instances they are absolutely correct in having NO interest in that Genome Scan.

3. " Who would give me the best explanation of its medical relevance: my GP, or 23andMe?"
Well, according to 23andMe's Terms of Service YOU CANNOT DRAW ANY Medical relevance from their "educational" test

I hope you see what I am getting at here. DTCG is at fault for not treating these tests as medically important in the first place. Are they medicine or not?

If they are not, then why should a doctor care about them?
If they are, then let's remedy this gap of knowledge. Rather than get all pissed, go out and try to teach some physician friends about this. Go lecture at your medical schools rather than sit in the medical school lab.

Just stop with this incessant "it's not fair, Genomic Freedom for all" crap!

Make a good argument as to why this shouldn't be regulated. I have yet to hear one.

To all,
Candles on Waxman's lawn is a show, just like SoHo was a show, just like zeppelin's are a show. The administration and the government sees this sort of thing as a sign that you are hiding something. Just go up to the Hill, state your case and let the chips fall where they may. Anything else looks like PR and political hype. Something which people can now see through.

This is not the end of DTCG, it is merely the beginning of a different type of DTCG, that's all.

If it's medicine, say so.
If it is not, say so.

Wow, some exciting posts. Not sure another opinion is needed here, but Dan, I have to agree with Steven. Yes, the FDA is a bunch of bone heads. Be that as it may, DTC is a failure because the product is frivolous. 23nme has the right approach--"genomics can be fun," because that's all it is at this point, a curiosity. If you think current analysis of a genome yields medically relevant information then you have been drinking too much Kool-Aid. Interesting information, yes. Medically actionable, no.

Just finishing re-certifying in Hematology, where our knowledge of genetics, in my humble opinion, is light years ahead of other fields. For example with germline risk of blood clots--we know so damn much about the genes and the biology, much better knowledge base than ALL other diseases...and yet the bottom line is that genetic testing in the absence of other medical risk factors is a waste of time. The studies just don't support doing it in healthy people.

Look, free advice!

Step One: find some actionable knowledge in the genome (not there yet!).
Step Two: "market" tests to MDs. BTW, investors, is there ANY medical diagnostic that makes money? Hm.
Step Three: consider going back to DTC.

Prediction: we will know when we are ready to move from Step One to Step Two when an MD gets sued by a patient with a bad outcome that may have been averted by having a genomic test. If genomic tests are so great, why hasn't that happened yet?

Michael T.
Thanks great points. I really truly agree. However, the likelihood of a lawsuit coming is probably from 2C19 and pharmacogenomics. I think that it will not be malpractice pre se, but may actually be a philosophy of law called Loss of Chance. By not ordering 2c19, in your case 2D6, did that patient with Recurrence/MI get robbed of a chance for a better outcome because you did not order that test.

This is a new philosophy, now upheld in 3 states

That lawsuit is coming, just wait.

-Steve

How exactly are these tests medicinal? They seem to involve no medical practice whatsoever. They do not provide medical care of any kind and they do not in any way manipulate the human body - for better or worse.

Are they not several elaborate statistical analyses broken down into probabilities? It is hardly different from a professional software analyst examining some code and informing another where the potential weaknesses are and what problems are more likely to develop.

The GTC companies should split their operations into 2 - simply providing consumers with raw data from their genome and selling them a software/statistical analysis of such. How that could be construed as medicinal, I'm not certain. The government-knows-bests will have to inform me how the FDA will provide any betterment as they nose themselves into this new arena.

@ Steve Murphy
Regarding your comment "I love how people who are not physicians and some who are not even research geneticists are here to pronounce how horribly not ready physicians are for handling genetic data." ...... I take a lot of offense to this. It isn't just the terrible "PhD geneticists" that you seem to pounce on, but an entire conglomerate of researchers; epidemiologists, statisticians, bioinformaticians, and yes, even clinicians have been involved in a lot of this genome research. It isn't as black and white as saying geneticists vs. clinicians. I believe it truly takes a multi-disciplinary team to understand what all this research means, how it applies to individuals and populations. AND, there has been vast amounts of research done showing that physicians aren't ready for this. Do they know more than the "average joe"? Sure. But does that amount to anything meaningful they can communicate to their patients? Right now, not necessarily. Good for you for getting involved in solving this problem (seriously, I think more needs to be done in this arena), I don't think Daniel MacArthur or anyone else would argue against this (sorry to be speaking for others). But the truth is right now, that 23 and Me could do a better job of interpreting the results!
Regarding whether it should be regulated? Loaded question, but I'll simply answer "Probably, on some level" ... if for no other reason than to get everyone to stop, think about what the test means, realize the meaning of the tests will evolve, and introduce the broader public to this discussion of what needs to be done to prepare for a (potential) era of genomic medicine and personalized medicine.

@Zack,
When the statistical analysis and probability estimate is about whether you will vote republican or not it IS statistics. When it is about whether you will develop debilitating disease, that's called medicine. Pretty simple.

How does that statistical analysis cross the line into medicinal practice? I don't see how that is so simple at all.

It provides no diagnosis or treatment. It's a risk factor, no different than generating a statistical analysis to determine how much more likely you are to die before 50 if you ride a motorcycle sans a helmet. An observation, analysis of data, then turned into a probability regarding your future life. Or is that medicine too?

To re-iterate what others have said in this invigorating post, I cannot see how you do not define DTC genomics as medicine. Let me back up a bit, if you submitted your DNA to a DTC company and then received ONLY your SNP list, solely a list of which polymorphisms you have compared to the reference genome, then I am OK with that. However, the second you turn around and begin to interpret these results and tell people what they are predisposed to or even worse which mutations and subsequent diseases they have, you are practicing medicine.

There is no doubt in my mind (and there shouldn't be any in yours) that some sort of oversight needs to happen in this case. You wouldn't let me running about town with a scalpel cutting people open and you certainly shouldn't be giving people medical information without the proper training or oversight. This usually comes in the form of the FDA or some alternative regulatory body. There is a simple way to avoid all of this nonsense and this is to follow my previous advice, test consumer's DNA and provide a SNP list only. Leave it to them to take this information to a doctor/qualified professional or look it up in dbSNP and see what they find. This is your right as a person and you are assuming all risks upon yourself. Alternatively, if you go to some form of licensed professional you can be sure that you are protected as a consumer and as a PATIENT.

Everyone is entitled to know the secrets of their own genome. It is part of what makes you fundamentally you and most people with any curiosity at all would likely want to see what they're made of. I know I would. Fortunately for me, my life's work is in science and genomics so I understand the benefits and more importantly the limitations of my genomic composition. 99% of the world does not. Let's concentrate on the education and interpretation of large-scale associative SNP analysis before we go ahead and throw the populous in the deep-end. We just took off our floaties after all.

@Zach

If you are told that you have a mutation in, lets say for example the GAA gene, and your mutation was one known to be the cause of adult-onset Pompe's disease; how have you not just been diagnosed? You've felt fine your whole life but now you've been told that you will have a debilitating disease as you age which will severely limit your functions, perhaps even leading to death.

Please explain to me how this is not medicine and how this does not beg for some sort of oversight over the agent administering this test? Even if just to the point of ensuring that all individuals handling your samples have been properly trained and documented as such. I am well aware of the ridiculousness of FDA regulations and I abhor all of the paperwork and endless documentation, but it all does really serve a purpose.

I want these tests to be readily available to all so that we can truly usher in the age of personalized medicine. That being said, what is so wrong with ensuring that we do it right? I'm a free market kind of guy, but I do not have 100% trust in the self-regulation of that free market. Do you?

I don't see how the presentation of that data (gene mutation) is anywhere equal to medical practice. How is it any different that providing the raw data and letting someone look it up on a 23andme.com database? It's just data. I trust the market to handle this one, that's for sure. These companies jumping through hoops will only drive up the costs for consumers and have a prohibitive effect on innovation in the industry.

@Zack

Let's try a real example. 23andSerge says "You have a founder mutation in BRCA1"

That is a medical diagnosis. You have just been diagnosed with a disease.

When they give you the full sequence data of the entire genome, that is not a diagnosis. When you compare it to a database and YOU find out that you have this mutation, you just diagnosed yourself.

A diagnosis of BRCA1 carrier without proper counseling and guidance is medical malpractice. You could sue a doctor for just giving you the information without guidance. Why in the hell would you expect any less from the DTCG company.

Which is "why" companies like Navigenics AND Pathway have physician and genetic counselors.

How can you not understand that the specific gene sequence is a medical diagnosis? I understand, if you look at DNA like computer code and say, "it is just code"

Well, when you say this code is for a disease it is no longer just a code.

BRCA1 mutation IS a disease. That is a diagnosis of a disease. Diagnosing disease is medicine.

It just so happens that the gold standard for BRCA carrier diagnosis IS the genetic sequence.

Vitamins don't diagnose disease, 23andMe does diagnose disease. That is the difference here.

Understand?

For those who don't know. BRCA mutations confers a risk of lifetime breast cancer of 85% and Ovarian Cancer up to 40% The treatment for this disease state is removal of ovaries by age 40, Medication and removal of breasts or increased Mammography and MRI.

So, I ask. How in the ever living bejesus is that not a disease and how is telling you that you have this mutation NOT medicine?

So if I get my own genome sequenced, hop online, and see what risk factors I have via a free database, that's cool. But if someone else looks at that same public information for me, that's a diagnosis?

It isn't diagnosing a disease because it is giving you a probability of developing a disease in the future. Telling a woman she has the BRCA1 mutation doesn't tell her that she does or does not currently have any disease. If it did, it would be a diagnosis. It doesn't - it's an enhanced probability of development.

PS: Your 2nd post on the issue did a wonderful job to disprove your own point as you highlighted the fact that it was enhanced risk rather than an actual diagnosis if disease. You could have picked a much better example, but I'm in no position to form your arguments for you.

Zack,
"Telling a woman she has the BRCA1 mutation doesn't tell her that she does or does not currently have any disease."

You have done it, I have now officially lost my cool.
People with mutations in BRCA1 have a GENETIC DEFECT in DNA repair that in and of itself is a disease.

Which also predisposes to other disease, namely cancers. Just like diabetes predisposes to heart attack.

It is obvious you do not understand human pathophysiology, thus your commentary is disqualified from any further debate on this topic as you clearly do not know what a disease is or is not.

Next time, look things up before you pop off saying what is and what is not a disease.

Just look up the ICD9 code for genetic predisposition to cancer. It is a disease code! DNA repair defect will be a code in ICD10.

Thus, I will not debate someone about the legalities of someone diagnosing another person with a disease as opposed to discovering your own disease status ON YOUR OWN!

I will not play stupid semantic games with someone who has no clue about medicine, genetic disease or mutations. Your lack of knowledge in this space is precisely why the FDA is investigating these companies.

Sorry to be so harsh, but this is the same CompSci 403 argument I hear all the time from people who have no biology or health literacy.

They don't get it, and that's why they can't understand why the FDA and Congress are investigating DTCG.

@ Zach

My example of a GAA (acid maltase) mutation at a specific locus is the diagnosis of the disease. You do not produce a functional enzyme and in this specific example (adult-onset Pompe's disease) you may feel fine now but you have just been diagnosed with a disease. You will certainly show symptoms of the disease later (if not already).

Some SNPs are associated with a risk for a certain ailment. You may get sick, you may not. Some SNPs cause a disease 100% of the time. No associations or probabilities. You got the SNP, you got a problem.

Therefore, with all due respect, please again explain how the discovery of a known mutation which shows 100% penetrance of a disease is not a diagnosis?

Jason, your example was a much more fitting of a diagnosis than Steven's, which is what I wished to point out. A risk factor for cancer is not the same as "you will develop this later in life, guaranteed." This is why his example was flawed compared to yours, despite what he may wish to call a "semantic game".

Steven, what is a disease symptom of the BRCA1 gene? Is there always one? Is it then a diagnosis or a probability? Do all of us not share SNP variation that may or may not manifest itself as a diseased state later in life?

Cases of 100% penetrance are the only logical (in my view) way to argue for a disease diagnosis based on genetic data. Would providing people with the raw data and letting them do it themselves, or with the help of additional software to comb freely available databases, free us from the necessity of FDA involvement? Because basically the argument there is that if someone else looks at the data and comes to a "diagnosis" (which is rather certain, as long as the sequencing is correct), the FDA need be involved. BUT, if I take the data they provide and combs the databases and do a "self-diagnosis", the FDA need not be involved? Seems like an odd, illogical conclusion.

In any respect, I thank those that take the time to discuss this in a civil manner without attempting to demean me. Even you, Steven Murphy, MD.

Using some of the arguments made here against DTC genomics

"A diagnosis of BRCA1 carrier without proper counseling and guidance is medical malpractice. You could sue a doctor for just giving you the information without guidance. Why in the hell would you expect any less from the DTCG company."

Sounds like I should sue my prospective life insurance company for giving me a surprise diagnosis of HepC, with the only counseling and guidance being "we've decided not to accept your application for life insurance". I would image there are other examples of exceptions to your argument. At least Pathway and 23andMe customers know what they may find out, and have made their own choice to find this out about themselves.

Will, I agree, personal choice and the seeking out of such data is important here - nobody is forcing this upon anyone - and Steven also states "Which is "why" companies like Navigenics AND Pathway have physician and genetic counselors" - looks to me like common sense, market forces, whatever you would like to call it, has taken care of this issue (to an extent) already. They certainly do a better job than the insurance company in your example.

@Zack
Only 100% penetrance is a disease? Seriously?
Glad you aren't my doctor or Genome provider.

Murphy, you shouldn't be so enthusiastic about getting the government involved and putting a microscope on things. Would your resume and practice survive a Congressional Hearing? (Rhetorical) Do you think this is good for Genetics, capital G? (Again, rhetorical)

Also, look, there are lots of things we do that are medically relevant measurements that are not medicine.

1) Getting on a scale at the gym. Your weight is relevant to medicine. But you don't need a doctor to weigh yourself.

2) Looking in the mirror. Your appearance is relevant to a whole host of medical diagnoses (e.g. yellowish cast for jaundice, or localized rash, etc.). But a doctor need not authorize you to look in the mirror.

3) Taking various nutrients and supplements to avoid a cold. Your diet is relevant to medicine. But a doctor need not authorize you to take some anti-cold medicine.

4) I don't need a doctor to look at WebMD or get on Pubmed if I have some bizarre condition. I care a hell of a lot more about my health than any MD will, if only because they have 1000 patients and I only have 1.

Etcetera, etcetera.

The solution to improved health is to decentralize and teach people more about taking care of themselves. The fact that GWAS associations have sucky signal strength is not a good reason for banning that movement.

I thank Allah that I work in the completely deregulated computer industry.

What if people stopped us from getting personal computers in the 1970s, assuring us that only experts in numerical analysis could do anything with it, and if we tried to design something on our own we might end up hurting someone since we weren't experts.

What if War Games in the 80s led to people banning individual access to computers on the network because of "hackers" and "national security".

What if the existence of buggy and crashy software meant that all software by everyone had to have premarket approval and go through ISO certification bullshit.

Imagine how much would be lost.

That is what is going to be lost.

Steven - Thanks for answering my questions.

Zack,
I don't mean to demean you. It is just a lot tougher to communicate concepts to someone who doesn't have the same training. Imagine a computer engineer trying to teach me intricacies of COBOL, etc over a few lines of blog comments. I just doesn't work.

I do wish you the best

If my 6 year old cousin was to get her genome sequenced and she had a mutation that could lead to cancer later in life, does she currently have a disease? First, nothing is wrong with her now, she has no symptoms of a diseased state. Secondly, it is not guaranteed she will ever develop the diseased state. I don't believe that's a semantic argument.

It is Semantic Zack
1. You state predisposition to a disease is not a disease state, when the biological defect to predispose is in fact a not normal physiologic (disease) state
2. It is a hypothetical and not true scenario
3. BRCA mutation state is defined as a Disease already

they were caught playing medicine. What about PGx testing Zack? Is that not medicine either?

Isn't PGx testing done in combination with prescribing medication? Of course that's medicine. The entire purpose of the testing is medical.

I really still don't understand this medicine vs. not medicine stuff. Steve seems to be saying that if it's defined as medicine then a medical doctor needs to be involved. But medical advice is given all the time by non-medics (from nurses to pharmacists). With DTC it's not "is it medicine?" but "is it a medical service of such a nature that it needs some regulating?". Probably yes, we do need some sort of regulation. The other question is "is there any level of advice that should be delivered only via a medical professional"? I can't see any use in taking extreme positions and remaining poles apart.

As Daniel says the FDA have had years to be working on this...I hope they have (been working) but unfortunately I bet they havn't, it's not the first time that they have been bounced into doing something about DTC, and I suppose they will fail again)

Would I need a doctor to discuss my family's medical history with my own family? Would that be considered medicine? The actionable information I may receive from a review of my own family's medical history would likely be more informative than a list of my own genetic variants (assuming we're not talking about known disease causing mutations), even if that list came with risk statistics.

Day trip to Tijuana, Piedras Negras, Vancoo, Niagara Falls or Nassau. Get it done there for 200 bucks.

No big.

Nice try, AMA. No banana.

"Make a good argument as to why this shouldn't be regulated."

Isn't this completely backwards? The burden of proof should be on the proponents of regulation to prove why the regulation is required. Given that no one is forcing genetic tests on anyone that doesn't want them, and that the companies involved provide appropriate disclaimers on the limits of their tests, this is one more of the many things that the government should just keep its nose out of. An individual's genetic data does not belong to the government, nor does anyone acquire a proprietary interest in it by virtue of an "MD" at the end of his or her name.

Isn't this completely backwards?

Why yes, yes it is.

And given the complete absence of evidence that receiving genetic risk predictions actually causes harm, the onus is very firmly on the regulation proponents to justify their point of view.

I think regulation is OK - it's the extent of regulation that could be the problem and the wisdom of any regulations that will be applied under the current conditions (controversy, knee-jerk, pressure from ignorants above, and a very fast moving field). Any restrictive control should, as said here, require strong justification with clear evidence of actual or potential harm and also be equally clear that shutting down DTC (if that were to happen) would not actually be harmful itself. I'm certain though that it would be harmful, for many reasons, most are in Daniel's post.

Excessive regulation would be terrible - something along the lines of the HGC proposed Code of Practice would be ideal and it embraces most of the points from Dan Vorhaus at Genome Law Report

@ SteveMD
I agree that this can be qualified as practicing medicine.
So what?
Why are MD's the gatekeepers of my personal biological information. They are the only one's allowed to give me information about my body?
I do not have an MD, but this is my body. I should have the right to ask and pay for any darn test I want on my own body without my MD's permission. If I want to know my D3 levels, why should I not be able to get that info without the consent of my MD? It is so frustrating.
Interpretation of the results is a different matter entirely. But simply getting the testing should be a free individual choice not restricted by government or MD's. It is none of your's or the government's business if I want to get my own genetic test. I don't need you to protect me from myself.

@ Ariel

I don't need you to protect me from myself.

Ahh, but apparently you do as the consumption of illegal drugs or of alcohol under the age of 21 are forbidden. Big Brother will send you to jail if you do not do what is good for you. Let's face facts here, the government of the U.S has taken an active interest in determining what is good for you and what isn't. This is the way it has been and is the way it will be. Regardless of how you feel about it this is an undeniable truth.

@Daniel

And given the complete absence of evidence that receiving genetic risk predictions actually causes harm...

As I am sure you are aware, genetic testing is not just the determination of genetic risks that can be cured with the panacea of a disclaimer. Some of the information that you will receive has the potential to be more than just the predisposition to disease or reaction to a pharmaceutical. You may actually be diagnosed with a disease if you so happen to find a particularly nasty SNP in your genome. This has enormous consequences to those who may be doing a genetic test for fun but then find out some truly sobering news. This is not to say that a doctor has to administer and explain the results of your-favorite DTC test but there certainly needs to be some form of oversight beyond submitting information to a website. These companies (or any other) need to have some form of accountability for what amounts to potentially delivering a clinical diagnosis.

@Jason
I don't believe getting information about your body is illegal - and the act of testing poses no risk.
To extend the point, I could really care less about current state of politics and invasion of government. It ebbs and flows. I am pretty sure our constitution stands, and article I section VIII providing limits on functions of government has not yet been repealed. So until then, you and the government can leave me alone to buy whatever the heck test I care to buy that is available to me. Why do you or the government care? Why should it be any of your business?
Also, god-forbid someone gets diagnosed with a disease by someone other than their doctor! The whole world is going to go down the toilet!!! Thank goodness a test like this is available, and thank goodness people can get a diagnosis early that hadn't otherwise been caught by their too-busy to take the time to actually run some diagnostics doctors.
I am only 31, but I like to know my baselines. I don't believe anything is wrong with me, but I love information. I want my D3 levels, I want my cholsterol, and i would love to have even more info but despite being a more-than-willing private pay client my doc isn't interested in ordering any of these labs. If I want to get any of this info, I have to go to the Cleveland Clinic Wellness Program and pay tens of thousands.
So shame on any of you doctors who think patients shouldn't have the right to get information about their body on their own. We are capable people, not ignorant morons who can't handle information about their own bodies. It is so insensitive and insulting the attitude MD's have towards us "patients" We are actual people with actual brains who can actually handle somethings without you giving us permission.

@Ariel

I want my D3 levels, I want my cholsterol, and i would love to have even more info

And wouldn't you want to be sure that the people who manufacture and distribute your test results are upheld to the highest quality standards and practices? Or do you also want to do your tests yourself in your garage.

Nobody here is arguing against these tests, certainly not me. This is about oversight, of which there is currently none very little. I am not a physician nor do I play one on TV, but your attitude towards your health is a little confusing. So you are upset that your doctor will not order needless tests for you to know your own "baseline". However, you are also upset that you can actually get these tests but they cost you a lot of money? Children want what they want when they want it.

If you truly desire to know any of your biological information which is not directly related to a health concern, then why are you upset that a doctor will not waste hospital/laboratory time on your curiosity? I would imagine that most laboratories are maxed-out dealing with patients who have genuine medical needs as opposed to your self-tinkering. If you want the tests then pay for them. Don't complain to me about the price of the tests, this is set by the market. If you want to have your genome sequenced, go right ahead and do it. But if you are going to try to extract medically-relevant information from your SNP list (which you most certainly are) then it needs to be regulated in some form. Just because the DTC-companies say it is not medical information does not make it so.

Here is a shiny red button. DO NOT PRESS THE RED BUTTON. You are entranced by the beautiful radiance and succulent aroma of the shiny red button. You are seduced by the subtle sophistication of the glowing omnipotence and benevolent charms of the red, candy-like button.... but for God's sake man, DO NOT PRESS THE RED BUTTON.

I am perfectly willing to pay for any and all tests, and my argument is that they should be more widely available - not more regulated and expensive. I support moderate regulation to a very limited extent. I am referring to a more general anger towards MD's and their authoritarian possessiveness of their power. It is bad enough I have to get an MD's permission to get my D3 tested.
I read things everyday, advice from Dr.'s like Dr. Oz, research studies, Dr. Roizen from the executive program in which I am involved, Sirius Doctor radio - they recommend you test for this, test for that, ask your doc about this, get your skin checked, etc.. When you actually follow through and do these things, doctors are annoyed that you are wasting their time unless you are suffering from some serious illness. That is not the way medicine should work. I am sick of having to go through an MD for every single little thing. There are such simple, harmless, basic things informed patients should have the right to do without bowing down to the almighty MD.
Because my doc doesn't have time, and is annoyed by any patient that isn't sick, and perhaps threatended by any patient who comes in with information, then I have had to join the executive health program. Very few people can afford this. So are you telling me that the average Joe shouldn't be bothering their docs with requests to keep up with preventative health and wellness? They don't deserve to know their levels here and there to make sure they are on top of things? It should only be for the elite? Regular MD's don't have the time and don't care? There is such a paradox between the public message to patients and the reality of what happens when you see your doc. I am sick of doctors thinking they are the only one's who know what is right for patients. We have the ability to research, understand, and think for ourselves. And if I see my doc for my physical and request a few tests, paying out of pocket, why the heck does it matter to her whether or not I get them even if she doesn't think I need them. Is the hospital trying to make money or not? I don't want to hear excuses about the lab being too busy with sick people that is offensive and ridiculous. I don't deserve preventative medicine? I am not sick enough? Unbelievable.

I do personal genomics in the East. We sell directly to the customers but we have MDs to interpret the results for them. So far no government agency is bothering us much yet.

I may be a bit biased. But I am with Ariel here. It is quite difficult to get docs to let us do tests on ourselves to satisfy our curiosity. I found quite many latent Celiac Disease patients (the double DQ2.5 carriers). And my work help them get diagnosed with CD and can take care of themselves better.

I agree that there should be regulations but they should only be limited to regulating genotyping/sequencing quality which is already covered by CLIA.

We all know 23andme et al are not doctors nor do they claim to be. If people do get BRCA positive result, I think they will then talk to real doctors for confirmation test and their professional advice.

I don't really understand why MDs here are against these tests, it seems to me they might bring more business to you.

Does anyone have evidence that risks of freedom in genetic testing outweigh the benefits?

Anyone? Anything?

Wow - I'm clearly late to this discussion but I'm going to jump in anyway. Starting from first principles: this is my DNA. A technology exists to help me read it, or at least part of it. Why do I suddenly need to recruit all the medical infrastructure to do this? I hope the medical professionals who want genetic testing kept under the "medicine" tent understand how appalling this argument is. It sounds like sacred knowledge being protected by an elite. Yes, yes, I know it's not that simple, but come on - you have to see the parallel.

Next step: My DTC provider dumps a list of SNPs, with no information or analysis. However, I go to snp-wiki and I find I have the minor allele for SNP rsX, which is 80% associated with dying horribly. Who, exactly, is practicing medicine? The DTC company? The database? Me?

Is it only medicine if there's an ICD code associated? Is it always medicine if there's an ICD code? Who decides what gets an ICD code - and more importantly, does this decision then render all related knowledge off-limits except with the advice and consent of a doctor?

Obviously the case is a strawman. A DTC company could not build a business around a raw data dump. But I can get my blood pressure and cholesterol levels checked with over-the-counter techniques. Does hypertension have an ICD code?

I totally agree with East that these labs should be regulated for quality, but it's my genome, they're my variants, and I've had them all my life. Why can't I read them?

@Traver,

I can understand why people not trained in medicine have a hard time understanding this.

Your blood pressure measurement IS NOT A DIAGNOSIS

Hypertension IS and can only be made after 3 BP measurements in the same setting.

Your ACGTs are not a diagnosis

BRCA1 Mutation carrier IS

No strawman, in fact a very important distinction in regulation AND liability. Which is precisely why we need to address it FIRST prior to applying regulatory frameworks.

-Steve

@Steve,

Thanks for the response. I think I'm beginning to see the root of the problem. It appears that, in the medical world, "diagnosis" carries a much broader meaning than just the condition it describes. "I carry a BRCA1 mutation" means just that, to me, but whoever gives me that info carries a whole load of legal, ethical, and liability baggage.

There's also clearly a gray area between personal health information (e.g. measuring my own BP over time) and formal diagnosis (I have hypertension). I can, with reasonable probability, come to the same conclusion as my doctor regarding whether my blood pressure is in fact elevated. We can acquire the same information. But the formal diagnosis of hypertension, not to mention the formal course of action following it, opens up a whole different world of, as you say, regulation and liability. And, frankly, I can see why a physician would be displeased with even that level of self-diagnosis: Joe Public's false discovery rate must be overwhelming.

In the few cases where genetic tests can predict disease, however, that gray area becomes a very sharp line: I either have snp X or I don't. Provided, of course, the test is accurate - but I think we all agree on regulating that. But the point is that it doesn't matter whether the test is done in the controlled, repeatable environment of a doctor's office or whether I'm spitting in a tube at home. The result is going to be the same.

I just don't think restricting access to that information is a defensible position. In the long run, anyway. I'm obviously betraying my ivory-tower academic roots here.

Have I completely missed the point? Is the distinction I draw between information and diagnosis artificial?

-Traver

I prefer to think whether my service can help people or not. If letting a person know about her BRCA status and it can prompt her to seek doctor's advice and save her life, I am all for it. I don't see any benefits for her by keeping her in the dark. A BRCA positive person without any family history as reference most likely won't take the BRCA test at any MDs' office. If my test can prompt her to do that, I think I do the right thing.

@Traver,
Absolutely brilliant! You've got it! If I give you the diagnosis of hypertension as your doctor, I am obliged to treat that disease and prevent progression as best as I can. If I don't I am liable.

If the DTC company tells you diagnosis, they aren't.

The same is true of genetic diagnoses.

@Geneticist from the East

I agree, but unregulated, how can I trust you are actually testing BRCA1???

WSteve

For tests that have well known diagnostic potential, I don't mind being regulated as well.

I assume Myraid is also regulated in the same way, right?

Goodness. The personal genomics industry wants to be "self-regulated"? Well, every industry on earth would love to be self-regulated, I'm sure. Heck, the oil and banking industries used to complain about "excess regulation" all the time, and we can definitely see just how well-founded their concerns truly were NOW, can't we?

Let's keep it simple here. The raison d'etre of governmental agencies like the FDA and the FTC is to protect consumers. If you have personal genomics companies offering their customers health-related information that their customers can't independently evaluate(not everyone gets to spend a decade in college studying human bio, you know), it's important that these companies be regulated to ensure they aren't ripping their customers off. As a geneticist, you're able to assess the quality of the product 23andMe sells you. Not everyone else is. The regulatory bodies are there to establish standards to protect the public, and that's precisely what one would hope they will do.

And of course I don't think these tests should be available to consumers only via clinicians. But more regulation is necessary and long overdue.

@Steve

I don't think 23andme claimed to test for the whole BRCA. So theirs is not a diagnosis. But you might think otherwise though.

"The raison d'etre of governmental agencies like the FDA and the FTC is to protect consumers"

No. The rationale is to (1) increase their budget and (2) avoid negative press, which are the only checks on their growth.

What incentive does the FDA have to "protect consumers"? If patients die because of lack of access to drugs, the FDA is currently not liable.

Work in the federal government and you will quickly realize that people are human and political there just as they are in business. The key difference is that businesses can go out of business if they don't serve their customers. The introduction of a regulator into a voluntary transaction between an individual and a business changes the dynamic. A regulator is your most important customer because they are the ones with a gun pointed at your head. If they don't like your product they will fine you, destroy your business, and throw you in jail.

This distorts every decision you make going forward. The regulator does not want new innovative stuff, they want stuff "according to spec". The regulator does not like it if you make a lot of money because profit itself makes them envious and suspicious -- they may not have your technical savvy or your gadgets, but they'll have your ass if they want it. They also now have something to trade: if they lay off your business, you give them a plush job as "director of regulatory affairs" the next year.
Thus it is regulators who corrupt business rather than vice versa. Take a third string PhD, give him a title, a govt job, and a gun -- and then empower him to fine and imprison all those innovative guys who surpassed him in college and grad school. "Those who can't do, regulate".

Nothing I say here should be surprising if you think of the police. Everyone knows about police brutality and the fact that police can and will ticket you if they feel like it or if they need to make quota. The FDA is exactly the same way; the main difference is that they treat entrepreneurs like criminals.

"But if you are going to try to extract medically-relevant information from your SNP list (which you most certainly are) then it needs to be regulated in some form."

Why?

My SNP list is mine. If I want to know it, and extract something from it, that is my business.

Why do I need permission from a group of people with a vested financial interest before I can do that?

Does the medical profession really think it has the right to control what I am permitted to know about myself?

In equity, it cannot insist that it must be involved in the process, and then insist that it has the right to control what I am told. If any other profession tried to do that, it would be roundly condemned, and quite rightly so.

@Sandgroper:

In principle I agree with you completely, but we may be talking about different things. If I'm going to extract medically-relevant info from my SNP list, then I absolutely expect that SNP list to be accurate, and that warrants some level of regulation.

@Traver - Yes, I'm sorry. I understand your point, and have some sympathy with it.

But regulation is no panacea. It will not prevent errors. I figure it's up to me to guard myself against possible errors, and Dan has told us some ways we can do that.

What I absolutely do not want is a physician-mediated process. That's what I have now, and I don't want any more of it.

"What I absolutely do not want is a physician-mediated process. That's what I have now, and I don't want any more of it."

I agree, but I also don't want the forbiddance of a physician-mediated process, either.

I'm certainly glad I have used 23andMe to examine some part of my own genome. Of course, the information available (both that is sequenced and, mostly, what we can make sense of now) is only a tiny part of my genetic information but this information is mine. I was born with it and I feel I have a right to it. There's nothing really amazingly fabulous or awful in it, as it happens. It's inherently very interesting to me simply because it is mine. I have a bachelor's degree in biology and with 23andMe's help I think I do quite a good job of making sense of the information.

Willful ignorance is not an effective argument against personal genomics

dgmacarthur — Sun, 14 Mar 2010 12:00:00 +0000

Willful ignorance is not an effective argument against personal genomics

Camilla Long's appallingly bad op-ed piece about personal genomics in the Sunday Times is a true masterpiece of unsupported criticism, and an ode to willful ignorance.

I'd encourage readers to discover their own favourite errors and misconceptions (there are plenty to go around), but here are some of the more glaring flaws:

Direct-to-consumer genetic testing is not illegal in the UK.

Long claims:

Although most of these tests seem pretty harmless and are marketed as "educational" rather than "diagnostic", in the UK such over-the-counter kits are outlawed.

She's completely wrong. In fact there's no law in the UK against DTC genetic testing, although it is illegal to test someone else's DNA without their permission.

Why doesn't someone writing an op-ed piece about personal genomics know this?

Learning of your genetic risk is unlikely to be harmful

Long profoundly exaggerates the risks of learning of one's own genetic disease risk:

Even if the tests were more accurate and reliable, what about the pieces to be picked up when the results come in? The cost to our collective mental health is incalculable.

Rubbish. There's currently no evidence to support the notion that learning about genetic risks of future disease do any long-term harm to a person's mental health, and growing evidence suggesting that such information does essentially zero long-term damage. For instance, the results of a recent study concluded that "[t]he disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks".

Plenty more research needs to be done in this area, but the notion of "incalculable" damage to mental health resulting from test results is utterly absurd, and entirely unsupported by the existing literature.

Willful ignorance is not an argument

The last half of Long's article is a paean to ignorance, peppered with disbelief that anyone might gain something from learning that they had increased disease risk:

And who -- in their right mind -- would want to know? I wouldn't. I'm already aware I'm at risk; that's enough. I certainly wouldn't want to know for sure that I was doomed -- weird, that -- just as I wouldn't want my children to worry about it, either.

[...]

Even learning small truths about your genetic code, such as where your ancestors come from, can be a weird experience... I had my maternal ancestry analysed (just for fun, honest)... I don't know what I would do with more serious genetic information and I don't know what other people would do with my genetic information, either.

Here's a hint: just because Camilla Long can't figure out what to do with information doesn't mean other people can't. There's plenty of people out there - people, I suppose, without Long's bizarrely fatalistic view of genetic information - for whom the knowledge of an increased genetic potential for heart disease could be enough to save their life.

There's even value to uncovering risk for diseases that can't be prevented: for instance, someone who knows they have an increased risk of Alzheimer's can learn more about the illness, prepare their family for the future, and ensure they've set aside enough money to pay for long-term care. Or does Long honestly believe that the only possible response to such information is to "have more fun in the short term, to buy that speedboat or get wasted more often"?

Researchers have already isolated genes that indicate if a person disagrees with alcohol. What if you've got a gene for seriously agreeing with it?

Let's think: what could you possibly do if you learnt that you were more susceptible than average to alcoholism? Can anyone think of any way in which that information might be useful to you? Well, Long clearly can't.

Space tourism is not an insult

Long finishes with what she no doubt regards as a knockout blow:

This is not an argument against knowledge. This is an argument against an expensive, largely pointless service endorsed by a celebrity for misleading reasons: it's the genetic equivalent of space tourism.

Firstly: actually, Long's article is an argument against knowledge; it's a clumsy, ill-informed dismissal of the notion that the information gained from genetic testing can have any benefits whatsoever to its recipients, laced with outlandish and unsupported claims of the dangers that testing can pose. It's a disgrace of an article of which she should be profoundly ashamed.

Secondly: the metaphor between space tourism and personal genomics is a good one, but not for the reasons Long thinks. Just as space tourism will result in the money forked out by a few wealthy individuals being converted into expertise and technology that will ultimately benefit others, so too will these first genomes - celebrity or otherwise - help to pave the way for medically relevant genetic information for the rest of us.

For an eloquent counter-point to Long's metaphor, see Jason Bobe's short and excellent opinion piece in praise of genomic astronauts.

Ignorance should be a choice

If Long wishes to stay ignorant of her own genetic risks - just as she has managed to remain ignorant of the entire field of genetics, even while writing an op-ed piece about it - that should be her choice. But her criticism of others who choose to pursue a greater understanding of their own genetic risk is entirely, horrendously misplaced.

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dgmacarthur Sun, 03/14/2010 - 08:00

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Very good. I wrote a comment on the Times site starting to list the errors (beginning with it NOT being illegal) - i got about 1/3rd of the way through and it was taking to long so i hit send, it hasn't appeared yet though...

Regarding any possible harm, DTC has been under viscious attack since at least 2002, starting in the UK, and the harm possibility was often put forward. Eight years later I am not aware of any harm being documented and I think if it had it would have been widely distributed by now. As you say, the work that has been published shows the opposite.

She says (about schizophrenia) "the idea that there might be a genetics-based solution for the disease, especially at this stage of scientific research, is absurd". She's correct, but then I don't know of any company that claims such a thing, so it's a useless comment.

And this "The impact on oneâs life of that kind of Damoclean diagnosis is almost impossible to imagine."

Enough - it's almost impossible to imagine what to say about that

"I had my maternal ancestry analysed (just for fun, honest)"

Just speculation but perhaps the lady was traumatized by finding out who her father was. :-)

"there's no law in the UK against DTC genetic testing"

Is there a law in the UK about providing medical advice without a medical license?

"Is there a law in the UK about providing medical advice without a medical license?"

Don't know but it's free to all and available, DTC, through NHS Choices website

@keith grimaldi
"Don't know but it's free to all and available, DTC, through NHS Choices website"

Sure, and so is the US Code at http://www.gpoaccess.gov/uscode and the US Federal Register at http://www.gpoaccess.gov/cfr, but that doesn't mean I can sell you legal advice. But by all means, read the law yourself and apply it for yourself however you like.

Awesomely savage work, Dan. Just a small point - this was the Sunday Times not the Times. For non-UK readers, our Sunday papers might bear the same names as the weekday/Saturday versions, but they're almost totally different entities with separate writing teams.

Great points! The profound ignorance of genetics exhibited by these anti-intellectual journalists never fails to astound me.

Sorry to be off topic.

I just noticed that decode raised the price of Complete Scan from $985 to $2,000. Anyone knows the scoop?

Thanks, Ed - an important clarification, given the Times' typically excellent coverage of genetics. I've modified the post.

Above and beyond some of the mistakes in this article, I just don't understand why people are so easily convinced of the benefits of DTC genetic testing? It looks a lot like the technological imperative. Genetics and genomics are beautiful and potentially helpful sciences but packaging them as commercial products and making the public believe that they are more useful then simply eating well, reducing stress and exercising is disconcerting. I don't argue the value of genetic and genomic research nor their use for monogenic disorders and for some complex traits but it's the profit-motivated blanket statement of "increased health for all" that is simply misleading.

@AndrewYates
"Is there a law in the UK about providing medical advice without a medical license?"

I don't understand your (and Sherpas) issues with what is medicine and what is not. Is it actually against the law to give medical advice if you are not a medical doctor? Is it against the law to give it DTC widely and freely as many government sites do (NHS, CDC, NIH, etc)? What about the pharmacist who advises me on medicines? What about buying ranitidine DTC in the supermarket? Where does medicine begin and end? What are the terms that define what has to be limited to a medical doctor and transmitted by the doctor directly to the patient? It seems that a lot of what you and Steve talk about as "doing medicine" apply to a whole load of stuff that is routinely done by non-medics, with no particular problems.

What makes 23andme with their (non-invasive) test "doing medicine" compared to say the NCI Breast Cancer Risk Assessment Tool? Especially as we are often reminded that classic risk assessments are more accurate than genetic tests. If that is the case then why is it not a problem that there are so many sites offering risk assessments with these more accurate algorithms, why are they OK DTC but genetic testing is not? What is the fundamental difference?

As far as I can see none of the DTC companies are making diagnoses or actually advising treatment - that I would agree is generally the realm of the medical doctor, but not always, unless it's against the law for my pharmacist to advise me to take a 'flu medication).

The lines are blurry and the regulation is poor but it's not clear why DTC is being singled out for your collective attacks. You may not like the marketing methods (I would say that you certainly don't), you might not think them useful as tests, on these I can understand your reasons. I don't understand your reasons for thinking that it's an illegal activity and that only medical doctors should be allowed to do it.

"Is it actually against the law to give medical advice if you are not a medical doctor?"

Yes.

"Is it against the law to give it DTC widely and freely as many government sites do (NHS, CDC, NIH, etc)?"

1) Medical science itself is not medical advice. An analogy is that a law citation is not a court order.
2) It's not unlawful for an agency of law to publish medical science ---even if edited for "layperson's consumption."
3) Merely viewing a website does not constitute a patient relationship.

"What about the pharmacist who advises me on medicines?"

What a pharm tech can tell you over the counter is probably more aggressively regulated than anything in a medical office. That's why they force you to sign so many ridiculous waivers.

"What makes 23andme with their (non-invasive) test "doing medicine" compared to say the NCI Breast Cancer Risk Assessment Tool?"

"Invasive" is a matter of relationship, not necessarily physical contact. "Information" itself cannot form a relationship with an individual to produce medical advice in the same way that the source code of software itself cannot to produce results.

Also: It's not unlawful for an agency of law to publish medical science ---even if edited for "layperson's consumption."

"why DTC is being singled out for your collective attacks"

That would be the subject of an entire editorial. Brief: because genomics belongs as common medical practice, and the way to achieve that is to shed the parties and the groupies and get serious about how to actually apply this in _actual practice_ rather than in theory.

Clarification: by "invasive" I do not mean "surgery."

In practice, "non-invasive" actually means "less invasive" with the implication of "less invasive than traditional surgery."

@keith grimaldi "The lines are blurry and the regulation is poor but it's not clear why DTC is being singled out for your collective attacks."

Ya know how Obama and the rest of the world are anti-healthcare profiteering? They bash "doctors" for escalating costs. Well, sometimes we have to do tests because a patient demands it. Why? House M.D., E.R., Grey's. WTF is hyping yet another unneeded scan on society? Go get an MRI/Plavix repsonder panel/BRCA test, it's fun to see what your brain/Genes looks like. Maybe it will empower you to eat Horny Goat Weed?

It is this blurring of bullcrap alchemy/charlatanism with serious medicine while portaraying it as not medical, but kinda sorta is.

Keep the serious, serious. BRCA testing is freaking serious guys.

In Anne and Linda's lame ass attempt to skirt laws they took the field of personalized medicine and shot it straight in the foot. Like little kids playing with their daddy's shotgun....Kabloowey!

Navi tried really hard to be serious, by only having a 9 night open bar in SoHo. Guys, WTF? You defend this $h!t? They have confused the field delivering mixed messages.

What should have been sold is "these genetic tests pinpoint with laser accuracy conditions and changes that will affect your health and medical care"

That is personalized medicine. Not Oprah shows.

So Keith, Does this clear up why we are trying to finish this off?
-Steve

Not really clear, maybe even less so. Unfortunate because the issue here is not parties or blimps but is precisely clarity and regulation, which are needed. For reasons given elsewhere my colleagues and I are fully behind the Code of Practice initiative of the UK Human Genetics Commission.

Iâm not defending the companies here, they can do that themselves, I am defending my wish to be able to genotype my DNA without having to go through a medic. I am defending DTC genotyping coupled with responsible interpretation (and marketing) for everyone who wants it.

I think youâre getting diverted by the 23andme bashing so letâs ignore them for now â itâs clear that you donât like their marketing but thatâs not my issue. What exactly do you want to âfinish offâ? Is it the product (DTC) or the way it is sold? I assume itâs the product and it would be good to read clear details of how you think it should be regulated. âDoing medicineâ is not helpful enough without clear boundaries â decodeme gives me medical information based on my genotype, it doesnât give me medical advice so according to Andrew Yates thatâs OK. These tests are sold as risk assessments, there are many disease risk assessment calculators available which donât involve genetics (and which maybe even more accurate at the moment) â should these only be administered by medics as well?

Is the Counsyl DTC service OK? Serious diseases, certainly not ear wax, but it seems to have been well received in the press. Where does the medic need to be involved? I think most would agree that if a CF mutation is revealed then the sensible thing would be to involve medics in the subsequent steps, the preparation for the disease and the treatment.

Andrew Yates says ââ¦because genomics belongs as common medical practiceâ¦â. Belongs? So it should be owned by? Why and who says so? It is appropriate to use genomics in medical practice but why does it belong only there? I appreciate that he also says that he needs an âentire editorialâ â I hope to be able to read it because to take ownership of genomics requires some powerful (and clear) arguments.

I think we have been crystal clear.

1. The Argument Against Marketing DTC as "Fun"

I think this warrants a blog post.

Put in one line

"If you are doing medicine say so"

Ok 2 lines

"Don't piss on my leg and tell me it is raining"

Got It?

-Steve

The UK Human Genetics Commission's "Common Framework of Principles for DTC genetic testing services" that Keith references was out for consultation last year. If you missed it - http://www.hgc.gov.uk/Client/document.asp?DocId=214&CAtegoryId=3

The question that seems most relevant here was:

2. Do you believe there are certain genetic tests that should not be offered direct-to-consumers? If so, which categories of tests?

The Principles do not suggest that certain genetic tests should not be offered direct-to-consumers. However, they do state the appropriate levels of support that should accompany testing.

The categories offered were:

1. Diagnostic tests
2. Pre-symptomatic tests
3. Carrier testing
4. Pharmacognetic tests
5. Susceptibility/Pre-dispositional health tests
6. Lifestyle/behavioural tests
7. Nutrigenetic tests
8. Phenotype tests
9. Genetic relatedness tests
10. Ancestry tests
11. Genetic matching

The section on provision of results (section 10, pp14-16) suggests that categories 1-3 and possibly 4 are likely to come with medical counselling recommended and a hefty regulatory framework, whereas the rest just need "appropriate levels of support".

With regards the seriousness of some current tests, question 4 helpfully illustrates the difference between "pre-symptomatic" and "pre-dispositional" testing:

It should be relatively easy for test providers, regulators and consumers to determine the category of a test that is either very strongly (pre-symptomatic tests) or very weakly (susceptibility tests) able to determine whether an individual will develop a condition: such as BRCA1 and 2 tests that are able to strongly determine the development of breast cancer and the T allele of rs3803662 located on chromosome 16q12 is only weakly able to determine the development of breast cancer. However, genetic tests that have a moderate ability to predict the development of a condition such as CHEK2 mutations that are associated with a 13% lifetime risk of breast cancer may create confusion and in turn lack of consistency amongst commercial providers as to the categorisation of tests. An approach might be to suggest a penetrance of 5% or more as an appropriate threshold for pre-symptomatic tests.

I can't tell if this is a work of towering erudition, or a classic British after-the-horse-has-bolted fudge. Or both.

Steve â if you donât mind I will reply to your blog post here (as long a Daniel has no objections either, I donât know if I am breaking the etiquette, itâs just to keep most of the discussion in one place).

Your post is much clearer and your position can be respected, it's one that many hold and there are many common points to agree on.

It's much more easy to understand when the language is less colourful and the personal insults are stripped out! - and your letter to the Nat Biotech editor was clear enough. I have no problems with language and insults, when they are used appropriately, but as you say this is a serious topic and deserves serious discussion.

Not all is clear, it never will be. When you say "Can someone OTHER than a pharmacist/doctor get access to medications? Not in the US" what do you mean exactly? Medications are available in Walmart and Target, even those that were previously restricted to prescription only such as Tagamet - are they not medications any more?

No problems with following laws, if they are there and you break them then you face the sanctions.

My wish is to have clear regulations whatever they are - the reality is that after nearly 10 years of DTC we are still not anywhere near them. This is why the HGC are pushing the Code of Practice - don't confuse this with industry self-regulation though, it's an initiative involving industry, academics, medics, regulators and ethicists (info and link on my blog). Without regulation a strong code of practice is a good option that would help consumers/patients and the professionals sort the serious from the dross.

One reason for slow progress on regulations is exactly the question of what to regulate - akin to what medications should be OTC and what should be controlled by medics/pharmacists. My opinion though is that while it may be preferable to do carrier and serious risk testing through a practitioner I still want to be able to do so anonymously and directly if I want. I don't necessarily trust other people with such information, however noble they may be they may have no choice when it comes to disclosure.

You don't like the way some companies operate, fine to go ahead and criticise them but donât conflate the whole industry into "parties & blimps, hip & cool" - maybe you don't intend to but often it's hard to tell. Many try to market medical information services in a responsible way. The language used may sometimes be tortuous or opaque and the disclaimers may offend but that is also a consequence of a highly proactive sector of the legal profession. All of the agency sites that run risk assessment calculators (NIH, CDC, NCI, ADA, etc), have similar "for information only, not for medical use" disclaimers, it's not a DTC thing and I donât think itâs something worth dwelling on anymore.

Another reason for urgency is that soon the "testing" part of DTC will be redundant. If decodeme interpret my DNA results from my 23andme test, are they doing medicine? They are certainly not covered by most of the proposed regulations, or even the in place regulations in Germany as all require the involvement of a biological sample. Interpretation sites are going to start springing up all over the place once genotyping / sequencing becomes commonplace, they will be unregulatable and they will sell all sorts of weight loss, child IQ, athletic ability, cancer prevention, erectile dysfunction rubbish. It's fine to have strong positions but we also have to deal with the reality of what is here now and what is coming.

King Cnut apparently was not so stupid, he wasn't really trying to push back the tide, he was trying to show to his people that it's impossible.

@Keith,

So let me see if I get what you are saying.

1. Regulations are fuzzy
2. The Definition of practicing medicine is fuzzy
3. There are a hoarde of charlatans and hucksters coming
4. We should give up standing for anything because there are too many of them.

Is that correct?
If so.

1. regs are fuzzy.

I agree, that is what the legislators and regulators are for

2. Def. of medicine is fuzzy.

Here is a litmus test.

Do you tell someone they have something that is classifiable in the International Code of Diagnoses?
If yes, you just diagnosed someone. That, is medicine.
That wasn't so hard was it?

3. The Charlatans and Hucksters are coming, a lot of them.

Why the hell do you think I am fighting so hard to get this shit straightened out now? We slept for 20 years and now need to move G-dDammit!

4. We should give up standing for anything because there are too many of them....

You can't be serious. Nothing is impossible. Complacency and unwillingness will do nothing to prove this.

Plain and simple.

If you are practicing medicine, say so
If you are performing a medical test, say so

the last group of hucksters who both you AND the medical community don't want to be associated with FCUkEd It Up.

Founders money removed from the company?

They FCUKED it up.

Hopefully the next batch does better........

"if it's medicine, say so"

and

"they fucked it up"

Come on Daniel. We're not all good chums. They fucked up, and now the bag man is here. We don't believe in aristocratic grace from behind the bag on this side of the pond.

@Steve - no you don't (get what I am saying)

1. I said I would welcome clear regulations, I also said that nearly 10 years of debate later (not everyone was asleep waiting for you to come along, but of course all voices and opinions are welcome at any time) we are still not close, so alternative proposals are necessary.

2. Itâs not so simple in reality and we all know that. Supermarkets sell medicine, pharmacists give advice that could be considered diagnosis, even if strictly speaking they are not supposed to. Paramedics make quick diagnostic & clinical decisions and save lives. If there are actually regulations in place that prohibit DTC testing for something like CF then these companies are breaking the law â if that is the case then the authorities are at fault here. Iâm not going to defend anybody breaking such a law just because I would prefer a different law

3 & 4. "We should give up standing for anything" How on earth did you read that in my comments? I think I was saying precisely the opposite. Given (1), my preference to inertia is to follow a strict Code of Practice that would require complete transparency in what is tested, what genes and variants are used, full bibliography, honest and accurate marketing, detailed descriptions of how the risk assessments are arrived at - read them please, the links are in my previous comments and also kindly provided by Neil.

Further I would say that the current group of companies have been quite faithful to the Code (23andMe, decode and Navi were part of the discussions from the start)and I wouldn't describe them as you do. I believe that the HGC code should be adopted widely, it's the result of the efforts of many individuals over many years actually doing something to improve the situation, we are far from unwilling and complacent.

There are some bad practices out there right now, they are very easy to identify. My recommendation to everyone is do not buy a test from any company that fails to follow the code - there are some companies that want several hundred euros/dollars without even listing the SNPs in the test but make outrageous claims. There will be many more coming which is why I said that there is urgency

@Keith,
Believe it or not, I have been following this for a little under a decade. Yes before DTCG.

1. Just because we have had debate, doesn't mean that debate is over. But what do you mean by not close. Do you mean, not close in defining what is medicine? Seriously? WTF is wrong? Did you diagnose? Did you treat? Did you prevent?

2. The paramedic issue is simply a red herring and B.S. EMT's and Paramedics receive healthcare training, unlike Python programmers and Rich Socialites that do V.C. work

3. The benefit to society of an EMT or Paramedic stepping over the line is pretty clear. Of a DTCG? Hmmm.

4. Why are regulators at fault? For not enforcing the laws? I would say CDPH and NYSDOH did an ok job with this. Not the greatest but an ok moratarium

Code of Practice is a good start and professions do this. Which is nice. But what good is the code if the code is "we are going to tell you exactly how we will be practicing medicine without licenses"?

There are indeed many charlatans coming. Why? They were emboldened by the lack of enforcement from the first batch....

It will only get worse from here. I hope we are willing to get back to the basics of saying what we do and why we are doing it.

If you do medical testing, say so. If you diagnose disease, say so. Don't say....hmmmm it's kinda gray here so I will err on the side of hazy and debatable. People are sick of that.

-Steve

Steve,

The result of CDPH's investigation was that 23andMe and Navigenics were in compliance with state law. Who are you to argue with them? What constitutes "practice of medicine without a license" is a legal question, not a medical one. Which seems curiously ironic.

The legal definition of the practice of medicine is not as fuzzy as has been suggested. But I am not a lawyer, so I'll just post the text of the section of the California code that seems most relevant:

2053.5. (a) Notwithstanding any other provision of law, a person who complies with the requirements of Section 2053.6 shall not be in violation of Section 2051 or 2052 unless that person does any of the following:
(1) Conducts surgery or any other procedure on another person that punctures the skin or harmfully invades the body.
(2) Administers or prescribes X-ray radiation to another person.
(3) Prescribes or administers legend drugs or controlled substances to another person.
(4) Recommends the discontinuance of legend drugs or controlled substances prescribed by an appropriately licensed practitioner.
(5) Willfully diagnoses and treats a physical or mental condition of any person under circumstances or conditions that cause or create a risk of great bodily harm, serious physical or mental illness, or death.
(6) Sets fractures.
(7) Treats lacerations or abrasions through electrotherapy.
(8) Holds out, states, indicates, advertises, or implies to a client or prospective client that he or she is a physician, a surgeon, or a physician and surgeon.
(b) A person who advertises any services that are not unlawful under Section 2051 or 2052 pursuant to subdivision (a) shall disclose in the advertisement that he or she is not licensed by the state as a healing arts practitioner.

@Anonymous
Now, I may just be a law abiding citizen. But I do see that your statement meets all the technical requirements of truth. Who am I to argue with Anonymous? Which seems curiously ironic.

"(4) Recommends the discontinuance of legend drugs or controlled substances prescribed by an appropriately licensed practitioner."

Do you think 23andme's Drug Response section can violate this part of law? Say if you find Plavix is not effective for you through 23andme, does that mean they recommend you to try alternative???

@Steve - "But what do you mean by not close"

I think I was clear about what I meant we are not close to but I still got a WTF from you so just in case it was not clear to others as well: We are not close to getting useful regulations for the oversight of DTC genetic services leaving room for all sorts of undesirable products.

Nothing to do with the definition of medicine - in fact I don't think there is much argument over the definition, the problem seems to be to define what areas of medicine can be performed by people without a medical degree, or maybe what are the actions that MUST be performed by a medic, as in the CA list above provided by Anonymous who also pointed out that these tests/services have been cleared by CA and NY.

A couple of your statements don't seem to go well together though:

"Why are regulators at fault? For not enforcing the laws? I would say CDPH and NYSDOH did an ok job with this. Not the greatest but an ok moratorium" ... "There are indeed many charlatans coming. Why? They were emboldened by the lack of enforcement from the first batch..." - This sort of sums up the clarity of the current regulatory environment.

Regarding your (2) and my B.S. paramedic comparison, are you saying that some or all of the DTC companies are relying on âPython programmers and Rich Socialites that do V.C. workâ to research and create the genetic reports rather than people qualified in science and medicine? If you believe that any of the companies are breaking the law then file a complaint. If you think that they are using dishonest marketing and making unsubstantiated claims you could take it to the FTC.

What use is a code of practice? It guarantees several things including transparency. No one in this field is clear on all aspects of what is OK and what is not. By saying clearly âthis is what we are doing, or intend to do, this is how we do it and this is whyâ we are allowing (a) possible illegal aspects to be clarified, (b) scrutiny of claims and (c) informed debate / review. All of which helps & protects the customer. Since whatever regulations or code exists there will always be dodgy goods then at least we need to have a situation where a consumer can be confident of certain products & services while also understanding that, for example, buying pills from an online pharmacy is risky. One of my biggest fears is that personal genetics may become as confusing as the supplement industry (and NO - just letting Medics control personal genomics is not the answer...).

http://www.bmj.com/cgi/content/full/324/7342/863
Melzer, D. & Zimmern, R. (2002) BMJ;324:863-864
Genetics and medicalisation
Genetics could drive a new wave of medicalisation if genetic tests are accepted without appropriate clinical evaluation

Given Ron Z seems to have based his career on this, and is one of the author's of the HGC guidelines doc, this nuanced editorial is worth a read - e.g.:

The genes that play a part in the pathogenesis of most common disorders are for the most part as yet unidentified and their role ill understood. Individually their predictive value is low, and at present there is little to suggest that they will have any greater clinical value than more conventional physiological risk markers, such as blood pressure or cholesterol concentrations. We believe, as do others, that the arguments for "genetic exceptionalism"---for treating genetic information and tests as somehow special---are not compelling. Outside the high penetrance, single gene disorders, genetic tests, like most other medical tests, provide evidence only of statistical risks.

Most physiological deviations are continuously distributed in the population, and most pathological processes give rise to a range of severity in clinical signs and symptoms. Clinical practice requires the establishment of agreed cut off points to identify disease and to separate people for whom treatment should be beneficial from other patients for whom the risks of diagnosis or treatment might outweigh the benefits.

Over time, the tendency has been to expand diagnostic and treatment boundaries, and to include in the "disease" category people with milder manifestations of pathology and lower levels of risk. Genetic tests for markers that may not result in symptoms for half a century or more could be new examples of a process of premature medicalisation---of attaching the "disease" label before it has been established that prevention or treatment is clearly beneficial. Treating the presence of a genetic marker as though it were the clinical disease can be very unhelpful.

We seem to be arguing not so much about whether there are "medical" and "non-medical" genetic tests, but who gets the right to decide which is which.

@Neil
I had a post on this 2 years ago entitled "pre-disease is the new disease"

We do this for other things. Pre-Diabetes, Pre-Hypertension.

We classify disease according to the International Classification of Disease 9th edition. The 10th is slated to come out soon and is going to be much larger.

When we are done, everyone will have some sort or predisposition. Think GATTACA.

The only question we are debating is, will we let unlicensed quacks practice medicine or test for disease? Or will we call it what it is and own up to it and accept regulations. Rather than avoid them in shady ways to increase market.

The market is NOT the US, or any other country with stiff regs. It is the East. That being said, quackery and withdoctoring are still practiced in places without these regulations.

Is that what we want our "health" companies to be? Regulation hiding, misrepresenting, devious profit driven ventures which currently have little value for mankind, but in the end could affect the lives of billions?

I am for real transparency. In marketing and utilization here.

@Neil

As for what a disease Is. It depends on what your definition of "is" is.

-Steve
p.s. I am done posting comments on this blog post. Our thread has nothing to do with Daniel's post.

@Neil

Thanks for bringing up the article - I've had several conversations with Ron Zimmern which had a lot of influence on my views on regulation. I can highly recommend the PHG Foundation as an excellent resource for public health genomics. They have a very interesting commentary on the recent German legislation which effectively bans DTC genetic tests "...a regressive and paternalistic approach that takes genetic exceptionalism to an extreme not seen in other jurisdictions. It is unclear upon what grounds this special treatment of genetic tests is justified..."

@Steve - 100% agreement, I have enjoyed Daniel's hospitality but we may have overstayed our welcome. Since there has just been some twitter about regs and clinical utility I have just posted a blog, excerpts from a related review we have written - Regulations, Clinical Utility & Personal Genetics

@Geneticist from the East
Do you think 23andme's Drug Response section can violate this part of law? Say if you find Plavix is not effective for you through 23andme, does that mean they recommend you to try alternative???

That's an interesting question. 23andMe itself promoted the idea that "most 23andMe users" should "enlighten" their cardiologists with this report ---presumably for Warfarin dosing. However, such a promotion would be an active promotion by 23andMe to its users to violate section three of the 23andMe contract which forbids such use. You can see so for yourself on 23andMe's twitter: http://twitter.com/23andme

I'm not sure who is in charge of legal compliance at 23andMe, but that seems to me like something that would void the clause protecting 23andMe from the regulatory definition of medicine in an unpleasant way. That would not be good for 23andMe.

Law for us but not for 23andMe, apparently. Apparently, the 23andMe contract is just fine for avoiding medical regulations, but perfectly and openly ignored in use, promotion, and whenever else is convenient.

I take it part of the context for #25 and #31 comes from this story from earlier in the week?

FDA's New Plavix Black-Box Warning Could Trigger Surge in CYP2C19 Testing
http://www.genomeweb.com/blog/fdas-new-plavix-black-box-warning-could-t…

The black box warning itself is at the top of the prescription sheet, and states:

Tests are available to identify a patient's CYP2C19 genotype and can be used as an aid in determining therapeutic strategy

linking to a section on the relevant genotypes - http://products.sanofi-aventis.us/PLAVIX/PLAVIX.html#S12.5

Most of the commoner "alleles" (haplotypes?) seem to be tested by 23andme
- https://www.23andme.com/health/Clopidogrel-Plavix-Efficacy/

As Andrew Yates, Steven Murphy MD and others have noted, whatever the 23andme disclaimer, this looks mighty close to being a DIY medical test.

I haven't had genetic testing done, and I doubt that I will; I'm old enough now that any genetic risks will probably have showed up.

But ...

This whole issue of "psychological damage" if you know what may lie in store for you: my mother died of Alzheimer's disease. So did her sister and her brother. Her two other brothers are in the middle stages. If there is any genetic element in Alzheimer's, then I stand a good chance of showing symptoms very soon now.

So I know as much as genetic testing, on that score, would indicate. Does that keep me awake nights? Not at all; it just led me to make preparations; my family knows who is to take control of my finances, when or if the day comes that I can't handle it. They know that they have permission to make decisions for me at that time, whether I want them or not. (We had problems with getting Mom to consent to outside care.)

My affairs are in order. I don't take on long-term debts. I don't burden myself down with too much stuff for my kids to have to clean up. And I enjoy each day to the fullest.

All to the good, even if I live to 100, sane and alert. Life is good, and better for my preparations.

As to privacy issues, any insurance or medical organization can look at my family history; I couldn't hide it if I wanted to. The same would be true of most people.

Personal genomics is getting serious: Counsyl emerging from stealth mode

dgmacarthur — Fri, 22 Jan 2010 16:00:00 +0000

Personal genomics is getting serious: Counsyl emerging from stealth mode

Disclaimer: my wife and I have both received and used free testing kits from Counsyl.

Counsyl is a rather enigmatic player in the personal genomics field: apart from a brief mention in Steven Pinker's excellent NY Times piece over a year ago and an even briefer post on a Newsweek blog late last year, the company has been in determined stealth mode for much of the last two years.

All that was publicly known about the company when I wrote about them last year was that they will be offering a large-scale carrier screening test: basically, allowing couples who are considering having a baby to test their genomes for a wide range of severe mutations that might - if both potential parents carry copies in the same gene - result in severe disease in their children. Couples who discover these types of variants could then arrange for pre-implantation genetic screening to be performed during the process of IVF.

While other companies (notably 23andMe and Pathway Genomics) do offer limited carrier testing in addition to their more "recreational" tests (things like ancestry and complex trait prediction), Counsyl's offering is intensely focused: the goal is simply to pick up as many known serious disease-associated mutations as possible.

There are two things I find particularly intriguing about the Counsyl approach.

The first is that the company appears to have convinced a number of large US insurance companies to cover the costs of the test, making it effectively free to a non-trivial fraction of potential customers; that will make the test accessible to a pretty broad slice of the public.

The second is that the company will undoubtedly face challenges from various quarters about the ethics of carrier screening. To me all such challenges are irrelevant in the face of the benefits of screening and, as the company's press release emphasises, there will be especially strong benefits of screening for minorities. Nonetheless, it will be interesting to see how this debate plays out over the next year or so.

For the last two years the personal genomics arena has been dominated by the testing of common variants with very small effects; it appears that this is just about to change dramatically.

Here's the press release:

Free with insurance, new pre-pregnancy test saves lives while dramatically cutting health care costs

STANFORD, California -- January 22, 2010 -- Genetic diseases like those seen in the new Harrison Ford movie "Extraordinary Measures" can now be prevented with a simple saliva test which is free with insurance for more than 100 million Americans.

The movie centers on the real-life efforts of the Crowleys, a Connecticut family trying to find a cure for a rare genetic disease affecting two of the family's three children. The condition wasn't detected until after their children were born.

Now, couples can take a Universal Genetic Test before pregnancy to determine whether their baby is at risk for more than 100 life-threatening genetic diseases. At-risk couples may then use a well-understood procedure called IVF/PGD to protect their child from genetic disease and ensure a healthy pregnancy.

This Universal Genetic Test was invented by scientists from Stanford and Harvard and brought to the public via a Stanford startup named Counsyl (counsyl.com). It is now offered by physicians at more than 100 prestigious medical centers across the country, including Yale Fertility Center (see counsyl.com/map), and has attracted the support of doctors from the nation's largest hospitals, prominent academics, religious leaders, and families with genetic disease.

Broad Support Among Prominent Physicians for Universal Genetic Testing

Dr. Pasquale Patrizio, Director of the Yale Fertility Center: "Every adult of reproductive age needs the Counsyl test. It is unusual in that it benefits all three parts of the health care triad: patients, doctors, and insurers. A child stricken by preventable genetic disease often dies in infancy and costs the bereaved parents millions in medical bills. A five minute saliva test that prevents this is a money saver, a time saver, and most importantly a life saver; it really is a no-brainer."

Dr. Thomas Walsh, Director of the Male Fertility Laboratory at the University of Washington: "Genetic testing has been recommended for all adults before pregnancy since 2001, but like many topics related to planning a pregnancy, awareness of this issue continues to lag. This test covers several key genetic diseases, including cystic fibrosis, spinal muscular atrophy, sickle cell, Tay-Sachs, and many others. The results of testing enable couples to make an informed decision before conceiving a child."

Dr. John Marshall, Chair Emeritus of Ob/Gyn at Harbor-UCLA Medical Center: "Because the test can be taken in the privacy of one's home as well as in a clinical setting, it reminds me of the first 'at home pregnancy test'. This 'at home carrier test' is very similar in that the healthy adults who take it generally test negative, with those who test positive referred for medical followup. It thus completely reshapes the debate over so-called 'DTC' testing -- offering this test over the web as well as in a clinical setting is simply a moral imperative, as it is the only way to get needed care to people in rural areas who may be far away from large hospitals."

Dr. Michael Levy, Clinical Professor of Ob/Gyn at Georgetown and Director of IVF at Shady Grove Fertility, the nation's largest IVF center: "Parents who know their carrier status before pregnancy can take preventive measures to have a healthy child. Because new techniques like PGD are used before pregnancy, they avoid the ethical dilemma of termination that was previously a roadblock to wider adoption of carrier testing."

Dr. Steven Ory, Past President of the American Society of Reproductive Medicine: "The vast majority of babies born with genetic disease have no family history. However, there are now tests available to prospective parents that can identify couples at risk of producing an affected child. That's why it's so critically important for all parents to get the Universal Genetic Test before pregnancy. "

The New Standard of Care at the Nation's Largest IVF Centers

Dr. Sherman Silber, Medical Director of the Infertility Center of St. Louis, and author of the best-selling book, "How to Get Pregnant": "Every adult thinking about having a child should get the Universal Genetic Test before pregnancy. The standard of care used to be to test at most one disease, and usually during pregnancy when the options were more limited. Now we can give couples this simple saliva test before pregnancy to cover dozens of diseases. It is a genuine breakthrough and one of the first real fruits of the Human Genome Project."

Dr. Arthur Wisot, Medical Director of the Reproductive Partners Medical Group in Los Angeles: "The Counsyl test is appropriate for everyone trying to conceive because it is the first test that is both practical and economical to screen for so many genetic diseases. Between the Counsyl test and preimplantation genetic diagnosis when positive results are found in both potential parents, couples can now protect their baby from developing any one of over a hundred debilitating and lethal genetic diseases with just a saliva sample. This test is the future of genetic screening."

Dr. Ian Hardy, Medical Director of Fertility Centers of New England: "We have been offering the Counsyl test to our incoming patients as part of their standard evaluation with exceptional results. It is an easy-to-use saliva test which is covered by most insurance plans and allows couples to be screened for major genetic diseases: cystic fibrosis, spinal muscular atrophy, Tay-Sachs, sickle cell anemia, and dozens more."

Dr. Kaylen Silverberg, Medical Director of Texas Fertility: "The Counsyl test replaces a battery of more expensive blood tests. It provides a couple and their physician with much more information for a fraction of the cost. Counsyl testing represents a quantum leap forward in pre-conceptual planning for couples - especially those concerned about having a child with a genetic disease - as it is safe, affordable, and easy to use."

Dr. Michael Soules, Medical Director of Seattle Reproductive Medicine: "Our clinic's new Preconception Program offers expanded genetic testing whereby the couple is screened to check that they aren't each a carrier for a serious disorder that could affect their offspring. The new Counsyl test is the simplest -- using just a saliva sample -- and most cost-effective way to do genetic screening as it checks for over 100 significant disorders with a single sample. Enlightened insurance carriers are paying for this test as it saves them the major future expenses of covering a chronically sick child."

Dr. Mark Perloe, Medical Director of Georgia Reproductive Specialists: "If you are planning to have children, you need to get the Counsyl test. Georgia Reproductive Specialists prides itself on offering our patients the latest advances in medical science, and we are now recommending the Counsyl test to all patients considering pregnancy."

An Advance for Women, Minorities, and Families with Genetic Disease

Professor Henry Louis Gates of Harvard University: "As the first genetic test for all ethnic groups, the Counsyl test represents a genuine breakthrough for minority health. With one test for diverse communities, African Americans and Hispanics can benefit from a new technology that actually reduces health care disparities."

Elena Ashkinadze, Program Supervisor in Genetics at UMDNJ-Robert Wood Johnson Medical School: "Because Counsyl's test simultaneously covers diseases from many ethnic groups at a considerably lower cost than standard blood tests, it promises to make carrier testing affordable for previously underserved patient populations, including African Americans and Hispanics. The current practice is mostly to screen once a woman gets pregnant. With Counsyl's test, we can change the emphasis to pre-pregnancy screening when more options, including preimplantation genetic diagnosis, are available. Ideally, women should understand that having carrier testing before pregnancy is as important as refraining from alcohol during pregnancy."

David Brenner, Director of the Dysautonomia Foundation: "As a parent of a child with a genetic disease, I wouldn't want another child to suffer from what my son has endured. Nothing is more important than safeguarding the health of our children, and this test is such a simple and powerful way to prevent terrible suffering."

Rabbi David Wolpe of the Sinai Temple in Los Angeles: "Several years ago, a mother whose son was born with Tay-Sachs said to me sadly 'The Rabbi made sure to tell us not play Wagner's march at our wedding, but said nothing about being genetically tested.' Ensuring that Jewish couples -- and others -- are genetically tested is a critical task."

Professor Steven Pinker of Harvard University: "Universal genetic testing can drastically reduce the incidence of genetic diseases, and may very well eliminate many of them." Last year, Professor Pinker and his wife, the novelist Rebecca Goldstein, took the test and learned that they were both carriers for familial dysautonomia. Their children would have been at risk for this life-threatening genetic disease -- underscoring that the value of genetic testing is far from hypothetical.

About Counsyl

The Universal Genetic Test was developed by Counsyl, a Stanford startup founded by social entrepreneurs and philanthropists. Counsyl's mission is to end the needless suffering of preventable genetic disease.

To ensure that every ounce of prevention enables a pound of cure, each test taken helps Counsyl fund treatments for children living with genetic disease. More than $50,000 has already been donated to nonprofits over the course of 2009. For the next month, donations will go to the John F. and Aileen A. Crowley Foundation in honor of John Crowley, the Notre Dame and Harvard Business School graduate whose life is the basis for 'Extraordinary Measures'.

Press Contact

Balaji K. Srinivasan

Counsyl

bk@counsyl.com

(650) 733-GENE

NOTE TO EDITORS: For additional information please visit Counsyl's website at www.counsyl.com. A list of selected clinics is available at counsyl.com/map.

'Extraordinary Measures' is a trademark of CBS Films. Other company, product, and foundation names may be trademarks of their respective owners.

Note: comments on this thread are disabled as I am currently on holidays and unable to moderate them.

attitudes towards genetic testing

dgmacarthur Fri, 01/22/2010 - 11:00

Tags

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pre-natal genetic diagnosis

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Technology

Blogger shares his increased type 2 diabetes risk with the world

dgmacarthur — Thu, 07 Jan 2010 09:45:00 +0000

Blogger shares his increased type 2 diabetes risk with the world

Genetic genealogist Blaine Bettinger has a fantastic post dissecting and contextualising a rather worrying result from his personal genomic analysis: a 50-60% increased lifetime risk of type 2 diabetes.

Blaine is unfortunate enough to be among the 1-2% of individuals who carry two risky versions at each of three major risk variants for the disease. (It's worth noting that type 2 diabetes risk is determined by many different genetic variants, most of which remain unknown, as well as environmental factors - so Blaine's discovery is very far from a certain diagnosis of the disease.)

Blaine's attitude towards the results is admirably pragmatic:

I, personally, am not afraid of my genetic information. I'm not afraid of any potential psychological effects it might have, nor am I afraid of any repercussions of sharing my genetic information with others. It is certainly clear that I lost the genetic lottery when it comes to diabetes risk, but there is no genome so perfect that it lacks at least one serious risk.

[...]

For me personally, interpreting my genotype is no more dangerous than the receiving the results of a home glucose test. Indeed, the results of the glucose test represent a current reality while the genotype merely suggests a future possibility.

I also applaud his decision to share this information with the world, a very personal way of demonstrating the spirit of openness to genetic data that he has consistently advocated in his posts. I completely agree with his reasoning here:

Although I won't go so far as to say that there is never any danger to anyone upon receiving genetic information, I will go so far as to say that it should be the individual, not the government, that decides whether the danger exists.

Amen.

Subscribe to Genetic Future.

dgmacarthur Thu, 01/07/2010 - 04:45

Tags

Thanks. Itâs interesting because here we have both genetics and family history. What would the naysayers say (apart from nay) about the results? Ha! â donât need the genetics, we have family history already. Really? What does Blaine learn from his results? He has, maybe, a raised risk of diabetes type 2, 36 people out of 100 with his genotype for these genes will get (do they mean did get?) diabetes, so 64 people wonât (or didnât). The genetics donât really tell us that whether Blaine himself has an increased risk or not - but then neither would family history. Of the 64 genetically similar people who wonât/didnât get diabetes there will be environmental reasons â this nice paper looks at diet plus diabetes GWAS SNPs and nicely shows the environmental influence (http://www.ajcn.org/cgi/content/abstract/89/5/1453).

Blaine now has genetics plus family history, the genetics may be warning him that he really needs to pay attention to the latter, or vice versa but it looks like the genetic component of the family history has not skipped him. With the Liu paper though, and many others from similar studies which I hope will be coming along soon, he can determine his fate by making sure that the environmental components do skip him. Well wouldnât he have done that anyway? I donât know, only he can say, but since family history exists and persists it would suggest that many with a history donât prevent it â add the genetics and I would suggest that we have an excellent tool for prevention.

But family history is better isnât it â it is the product of both genes and environment? Not always. A Pima Indian moves from Mexico to his cousins in Arizona, two generations later a family history of a disease that he/she had never heard of is now established in his/her lineage.

OK the genetic results look interesting but how do we know they will be really useful â will they actually have the magic ofâ¦clinical utility? Letâs find out by finding a few thousand people with a similar high risk profile, in some weâll use the results to guide prevention, in others we wonât, plus all the other controls required etc etc, and weâll wait, and wait, and wait a bit more (Blaine is not so old I donât think), then weâll find out 10-20 years later, but at least weâll know and after all âif RCT data are considered necessary to understand beneï¬ts vs. harms for a particular application, then so be itâ (http://bit.ly/6jwZyE)

Has family history as a preventative tool for diabetes ever been subjected to an RCT of the type being demanded for genetic profiles, for each particular application? Has it been tested for potential harms (worried well, false reassurance and all that)? These are real question, Iâd like to see the designs to understand if they could be used in genetics.

Personal genomics will make it through the difficult early years â maybe it was Henry Ford, or maybe not, but to paraphraseâ¦if he had listened to the transport industry at the beginning of the last century he would have been asked to develop faster horses

Hi Keith,

Fair points all. Regarding cases where genetics trumps family history, perhaps the best example is recessive diseases such as cystic fibrosis: most people with CF have no family history of the disease, because very few of their relatives are unlucky enough to have inherited two mutated copies of the CFTR gene.

It's clear that there is a need for studies exploring the effects of genetic risk information on health outcomes, but it is ridiculous to argue (as Khoury did in his recent debate with Kari Stefansson) that we need to wait for the results of these trials before people can be given access to their own genetic data.

Keith â very interesting and thoughtful comment!

I canât say how others will or do respond to their genetic information, but I can tell you how it was for me. I consider myself to be a moderately intelligent person, but up until this point in my life (Iâm 33) Iâve largely ignored the environmental factors for type 2 diabetes. This despite the fact that it has killed a member of my family! But, for whatever reason, realizing that I have these serious genetic risk factors spurred me into action. Iâve made some serious positive life changes as a result of my genetic information, even though I knew beforehand that those changes needed to be made.

Although family history most certainly has its place, itâs not the only answer for everyone. It appears that at least some people will respond to genetics more than they will respond to family history.

What if I hadnât been allowed access to my genetic information, or had decided not to jump through whatever hoops the government set up for me? Iâd like to say that I still would have made these positive life changes, but Iâm not so sure.

Although Dr. Murphy just posted today that âYour genome is essentially worthless right now,â (http://tinyurl.com/ycnkcbn) I couldnât disagree more. Although it sounds a bit dramatic, my genome has potentially saved my life.

Great post by Blaine and excellent comment by Keith, above. From a public-health perspective, one of the biggest questions is what Keith highlights, What will people like Blaine do in terms of lifestyle changes (that they wouldn't have done without genome-based knowledge of risk)? How will such actions affect long-term health?

Makes me want to see what Bob Green's group at B.U. has published recently; he has been running a study to look at the effects of knowledge of ApoE genotype on people's lives (APoE being a strong predictor of risk of Alzheimers disease). Though "what to do" in terms of modifiable environmental factors is much less clear in terms of AD than is the case for Type 2 diabetes.

Thanks AMac. Daniel I completely agree with you that it's ridiculous to wait. We all need studies, industry needs them for commercial reasons and the consumers for confidence. Studies will make the products better, it doesn't mean that they have no value now. It would be more helpful expending energy on practical alternatives instead of continuing to argue for impractical RCTs.

In their article referred to they say "absence of evidence is not evidence of absence" - clever(?) soundbite but not an argument and not relevant - but, i don't believe it is true anyway, not in this case. Since 2001 some there have been very strong opponents of personal genetics/DTC who have been searching but not finding evidence of harm. As far as harm is concerned, consumer protection works both ways - delaying a potentially useful service because "it might" do harm is potentially harmful itself.

Seat belts can and do cause harm, some people would have been better off without them. Enough with genetic exceptionalism (even though it is exceptional in many ways!) - a vain wish, but at least there is good leadership from the likes of the UK HGC and the Code of Practice Proposal: http://bit.ly/8I8xlN. If they were widely adopted then a lot of the murkier offerings would go away.

Thanks Blaine for the follow up, it's very interesting to know how you will respond, and a satisfying result especially because the lifestyle changes made now will certainly be less dramatic than those that would be required by leaving it too late. There is stuff and nonsense about creating the "worried well", but perhaps a lot of the well have a good reason to be a bit worried and perhaps the genetics will help them to learn more about what to worry about and how to do it - and become less worried in the process!

AMac - thanks for pointing to the work on AD/APOE, you're right, it will be very interesting to see what are the responses to testing for this quite controversial gene. As you say there is no well defined intervention, there are some interesting pointers but nothing solid, this doesn't necessarily make the APOE gene knowledge useless to those who want to know it

Larry Parnell has an interesting comment on this and their gene-environment work on TCF7L2 over at his blog http://bit.ly/90Jh3i

Here is a link to more information about the genetics of Long Chain 3 Hydroxyacyl Coenzyme A Dehydrogenase Deficiency that was prepared by our genetic counselor and which has links to some useful resource for those dealing with this condition: http://www.accessdna.com/condition/Long_Chain_3_Hydroxyacyl_Coenzyme_A_…. There is also a number listed for anyone who wants to speak to a genetic counselor by phone. I hope it helps. Thanks, AccessDNA

deCODEme's embarrassing data processing glitches - lessons for companies and customers

dgmacarthur — Tue, 22 Dec 2009 06:15:00 +0000

deCODEme's embarrassing data processing glitches - lessons for companies and customers

Late last week I noted an intriguing offer by personal genomics company deCODEme: customers of rival genome scan provider 23andMe can now upload and analyse their 23andMe data through the deCODEme pipeline.

On the face of it that's a fairly surprising offer. As I noted in my previous post, interpretation is what generates the real value for personal genomics companies, so giving it away for free seems a bizarre approach to business - especially for a company living on the edge of a financial precipice. However, I also argued that the intention here is likely to be to generate an opportunity for deCODEme to display its interpretation skills to otherwise entrenched 23andMe customers, in preparation for the upcoming battle for interpretation supremacy in the whole-genome sequencing era.

In digging back through my archives I realised that this isn't actually the first time that this strategy has been employed in the personal genomics game: back in June this year, 23andMe offered its interpretation service free to customers of Illumina's freshly-launched $48,000 whole genome sequencing service (the original source is this subscription-only article in industry publication In Sequence).

It's nonetheless the first time that a personal genomics company has opened itself up to genome scan customers, and it's certainly a disruptive (and potentially game-changing) move. AccessDNA's Jordanna Joaquina even goes as far as to speculate that this may herald a shift in deCODEme's strategy towards pure data interpretation. I personally think this is unlikely for deCODEme itself, but I wouldn't be shocked to see a proliferation of multi-platform interpretation services over the next 12 months (Knome's recently announced discovery service is a step in that direction).

But creating an interpretation service that can deal seamlessly with data provided in a multitude of formats from different providers can be a challenging task, as deCODEme learnt in a particularly embarrassing manner this week:

Nothing seems to be going right for DeCode Genetics, the Icelandic personal genomics firm that declared bankruptcy last month. In an attempt to win customers from its Californian rival, 23andMe, DeCode has offered free analyses for anyone who uploads their 23andMe data onto its website - only to produce mangled interpretations for genetic ancestry.
More alarming, from my point of view, the company also suggested that I have a 40 per cent lifetime risk of developing Alzheimer's disease - which if didn't know better thanks to previous scrutiny of my own DNA, would have been a devastating thing to learn.

The article, from New Scientist's Peter Aldhous, details a series of blunders in deCODEme's management of the 23andMe data transfer, compounded by an embarrassing "Reply All" incident in which deCODE's press officer Edward Farmer accidentally forwarded a dismissive email back to Aldhous.

The ancestry problems (outlined in detail by David E.) seem to have resulted from deCODEme relying on an outdated data-set from 23andMe to test their software, something that was rapidly fixed (see screenshot from my own data below). But the Alzheimer's risk prediction error is the result of using an imperfect proxy marker within the APOE gene - a seriously dangerous thing to do for a variant with an unusually large effect on disease risk.

What's the big picture here? Well, obviously 23andMe customers porting their data over to deCODEme should take the results with a grain of salt - but that's true for anyone looking at personal genomic data anyway. These errors shouldn't discourage anyone from checking out their data on deCODEme's interface, and indeed I'd strongly advocate that all 23andMe customers do so in order to get a second (imperfect, but nonetheless informative) perspective on their own genetic data.

This is also a timely warning to everyone - both customers and companies - starting to move through the personal genomics space. The next few years will see a proliferation of data formats and interpretation services, and there will inevitably be errors made due to clashes like this one. It's important that companies do their best to minimise the effects of such errors (and deCODEme could certainly have done a better job here); but it's also crucial that personal genomics customers follow Aldhous' example in constantly questioning their data, finding inconsistencies, and following them up until an explanation is found.

This is your genetic data, and you deserve an accurate interpretation - but in these early, chaotic days of the personal genomic industry, that means playing an active role in interpretation yourself.

Subscribe to Genetic Future.

My ancestry data immediately following my initial upload on 17/12/09 (note the bizarre X chromosome results):

And then following the bug fix, today:

dgmacarthur Tue, 12/22/2009 - 01:15

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