As clearly stated in the Consent Form at 23andMe:

Genetic Data: The laboratory processing your saliva sample will analyze your DNA to determine your genetic information. The laboratory will not analyze your saliva for any biological or chemical components, markers or agents other than your DNA. The laboratory will not have access to your name or your other personal information. A unique bar code will allow 23andMe to link genetic data derived from your sample to your account. After analysis, your remaining DNA and saliva samples will be destroyed.

Account Deletion: You have the right to delete your genetic information from our systems. Within thirty (30) days of receiving your written request, we will delete your account, and your information will not be included in any future research, including future research by other organizations. Any research conducted prior to the end of the thirty (30) day period following receipt of your request will not be altered or halted. Once your account is deleted it will not be retrievable. For purposes of clarity, any user-generated content you contribute will not be deleted and your genetic information associated only by barcode may be retained at the laboratory. Click here for more information.

Given all the angst in the community, I assumed that there must have been some recent clarification, because I have written records here of my own confusion, and it is a common sentiment in the community that somehow 23andMe is unethically hoarding user DNA.

Nope. I bought my 23andMe kit sometime in winter 2008 and received my kit in March 2008. At the time, I photographed and scanned all the pieces of the kit —including the Consent Form— which I then emailed to my gmail account for safekeeping. Here you can see the same statements above printed in the Consent Form from at least March 2008.

This is an alarming oversight on behalf of me and the community. However, I would also like to highlight two more statements from the Consent Form:

You should not change your health behaviors on the basis of this information.

Furthermore, 23andMe’s service is not a test or kit designed to diagnose disease or medical conditions, and it is not intended to be medical advice.

I hope 23andMe’s marketing and PR is very very careful about misrepresenting their product in the media, which of course, they quite clearly hope to be a health company, so of course they are misrepresenting their product to some degree. However, I’m really feeling too cynical right now to make a call one way or the other. Everybody incessantly talks, but nobody ever says anything, and it’s getting to me.

Update: oh wow, it turns out that the 23andMe contract always has stated that 23andMe destroys the sample after testing and will delete data on demand (at least, since March 2008). Full story coming. A lot of people have a lot of explaining to do…

Quickly: a few people have asked me to update my opinions about 23andMe. My previously stated opinions have not changed (I’m a customer of 23andMe, and I like it). Further, I don’t have strong ethical ideas about consumer products. 23andMe is a nerdy toy —like a novelty x-ray— not medical advice, and as long as 23andMe continues to organize and present good scientific information, I’m happy. Generally, I think that 23andMe sets a high standard for transparency, scientific tool usability, and responsiveness. Particularly, Andro Hsu, the Sci-tech liaison has been great, and 23andMe continues to make responsible adjustments. For example, I suggested a few months ago:

…Keeping the saliva sample violates medical research conventions, and that offends the ethical standards of others in the medical research community….

Solution: Add account deletion to the main FAQ and promise to destroy the saliva sample on account termination.

Apparently, 23andMe agreed and now destroys the saliva samples.

I think that there will be issues in the near future as “geeky toy” evolves to “obvious medical advice,” but I expect 23andMe to handle these growth issues responsibly.

What I don’t like about 23andMe is its wholehearted embrace of the American marketing culture and its media games. Unfortunately, that’s how business has to be done today, and I’d probably do something similar if I ran 23andMe (though my approach would be significantly less… estrogen-y…). Startups don’t have the luxury of non-commercialism, and most news media isn’t anything more than a marketing expense a few companies removed, so relax.

What I don’t like about the community response to 23andMe is when people seize on some tiny detail and spew some diatribe without actionable rational discourse. Transparency is so vital to good medicine, and attacking a company for every statement not prepolished by some PR shill strongly discourages transparency. That is wrong. Really, not every off-the-cuff statement by a company officer is a medical emergency. Significant medical misinformation must be corrected, but transparency is much more important to the future genomics industry. The significant medical misinformation I see doesn’t come directly from 23andMe, it comes from the parade of media bots swarming about the celebrity of the company. I can’t say the same for other genomics companies…

I certainly have my complaints about 23andMe, but I try to keep them to myself until I have something intelligent to say about them. And yes, I have willfully “picked a side” in the interest of pragmatism, though my real alligance goes to Coriell whom nobody knows much about, but that is the cost they incur because they don’t play the stupid media games. They are also less driven to “capture a market” because they have been a medical research institution for several decades, and judging from their huge warehouse of nitrogen-preserved cell lines, they expect to exist forever.

Incremental Agglomeration, Creative Destruction, and the Impending Forest Fire of the American Medical Establishment

Part 1: Introduction

The great promise of every modern medical initiative has been “cost savings.” Indeed, what magnanimous medical aspiration in print or powerpoint could preclude a fast-fact stat about the alarming overspending in American healthcare? Yet, as America continues to realize these health initiatives —ostensibly in the spirit of “cost savings” —yet, health spending inexorably grows despite typically marginal improvements in care.

Electronic records, evidence-based medicine, patient-centric care, personalized medicine, universal coverage, and genomics —sure, they all sound good, but can America afford another revolutionary “cost saving” medical industry initiative? No, because revolution is destructive, and what institution willfully destroys itself? Not institutions that still exist. So like the non-directive flaws of biological group selection theory, the drastic improvements promised by revolution are beyond the incremental and self-sustaining mechanisms of institutionalism —as intellectually unaesthetic as that may seem.

Every new medical initiative purports revolution by some combination of better education, savings, standards by implementing some new discovery, invention, or idea. But there’s no grand medical conspiracy inhibiting the potential of these ideas; the mundane simplicity is that change is hard work, people are busy, and everyone stakes in the status quo.  Only outside competitors are willing and able to metabolize the medical establishment, and while these well-minded initiatives may snuff immediate needs, rather than sparking significant change, they continue to agglomerate like a thicket. Thus the longer revolutionary fire is procrastinated, the more dead wood accumulates, and the greater the inevitable conflagration in healthcare will be.

But today, two decades of information technology has made healthcare revolution imaginable. First, medicine has matured from scholarly practice to information science, and science needs no priesthood. Next, decades of accumulated initiatives choke American healthcare in waste information, a problem information technology solves well… too well. From problems like “pager tag” to communicate simplistic information like blood pressure and on-calls to “governance by bureaucratic harassment” like insurance coding and liability threats outside strict procedure, the revolutionary solution destroys the existing systems and their vested interests. But, destroying useful systems is locally suboptimal, and institutions can act for their own immediate growth and survival. Thus, revolution is fundamentally unachievable by insider initiatives despite theoretical feasibility and best intentions. So finally, a willing and able outsider is necessary to imagine revolution, and the elite groups behind information technology giants like Google have announced their revolutionary intentions with ventures like 23andMe and Google Health. However, revolution is unpredictable, and by the power of the Internet, the eventual leading health revolutionaries could be anybody.

So manifests the quintessential American pragmatic hypocrisy: all tout the wealth-building virtues of creative destruction until the torch of change is under you. Then, change is “unethical.” Only law is more artificially sustained by its own ethical sophistry and willfully abstruse erudition as is the gross establishment of American health. America hates its healthcare, revolution is coming, and no insider medical initiative can stop it forever.

This is a four part serialized essay which will discuss what a revolution in health will and will not look like, why revolution is possible today, and why direct-to-consumer genomics is sparking our imaginations. Subscribe to Think Gene to be notified when new sections are published.

[1] Introduction

[2] Picture of Revolution (coming soon)

[3] Why Revolution Today (coming soon)

[4] The Spark of Direct-to-Consumer (coming soon)

Oh no, my 23andMe!
By, Adoph “Nightwing” Hilter

Oh no, My 23andMe!
Please don’t make me
get an IRB.
If only everyone would forget about me
and not link my wikipedia entry
and call each other “Nazi”
in every popular book about genomics, there is me
in every talk about medical research you dislike, “you Nazi!”
because whatever minor procedural bureaucratic violation with which you disagree
is just like torturing millions of people
and here I brood in my nihilistic eternity

My Mood: Angsty
What I’m doing right now: Definitely not getting an IRB! YOUR NOT INVITED TO MY SPIT PARTYS STEVE!!!!!!1

UPDATE: Steve has responded forcefully to this at Gene Sherpas.

Dr. Steven Murphy, “The Gene Sherpa” has nagging me to write this…

Steve is upset that DTC genomic startups, specifically, 23andMe, aren’t following “protocol.” He listed a bunch of institutional policies and standard procedures that I don’t care to remember in mind-dump blog post he’s since removed, and used these “violations” as justification to decry 23andMe and friends as reckless and unethical.

So I’m in New York City with Steve, and I say: “listen, Steve, the first thing anyone in Silicon Valley will think when you prescribe a stack verbose regulations will be ‘how can I ignore this?’ These people, who are the same people of scientific marvels like Google, have a dim opinion of all bureaucratic authority —including medical authority— and for good reason. Nobody there cares what some document says, they only care why those legacy policies exist and what problems they’re supposed to solve. Why? Because they think that they can solve those problems better. And you know what? They probably can.

“So, if you want to help —if you truly want to do good— rather than rant and be willfully ignored by your targets, then you have to simply state the problems, why they’re problems, and suggest a simple, non-authoritative, actionable way to solve them.”

(Also, Steve doesn’t want to provide free consulting to Coriell’s free genomic test’s competitors because he probably has a special surprise for the people of New York, but deals can fall through, so I’ll wait until the contract is signed before talking.)

So, here they are:

1) Transparency by Independent Expert Oversight

Problem: If a company acts unethically, how will public know about it, and how will the public know when it’s fixed?

Somebody must be both empowered and responsible for the ethical operation of a company obviously and independently.  That way, when we hear no reports of problems, it’s because we know the company is operating ethically, not because there’s no way to report problems.

Question: Who in DTC genomics is responsible and empowered to report problems?

Why This Problem Matters: Genomic testing companies are a new blend of software, health care, and private medical records. Very few ethical issues matter in information technology itself, but health and medicine are especially fraught with ethical concerns. It’s necessarily yet not sufficient to “don’t be evil.” The greater the ethical risk, the greater confidence the public must have in the company, and the greater the transparency must be.

Solution: Appoint a small board of diverse experts appointed to passively oversee the the company’s operations and report problems to the public in a standard and obvious way.

Is this a necessary expense? No: it’s unlikely to appeal to the press and general public and generate immediate sales. But it does improve the long-term company image as seen by the informed and the medical research establishment. I notice that 23andMe is hiring a durrbizdev. New bizdev director, this board and the act of forming it would be the single most effective “business development” initiative for these people. Throw in some keep-it-real black projects preacher, some Berkley femnazi community leader, and a some whiny tech author in glasses with too many degrees and you’ll have yerself a durn fine SWPL media event, ripe for plucking clean off the press release vine and right inta them hungrylike New York Times media basket. Plop. Feed ‘em fer a week, ya know?

A similar board may already exist, but that it’s private, poorly publicized, or not well defined. Define it, publicize it, spice it up as noted above, problem solve.

Existing Policy: The existing policy is to form an Institutional Review Board (IRB). Steve could certainly speak better about this, but the end result should be implementation of my simple statement solution.

Is it a necessary expense to use existing policies to form an official IRB? My suspicion is that existing policies are painfully slow, abstruse, and expensive, but existing institutions will to trust you more if you use them. They’d be suspicious if you created your own policy, even if your policy is better, because usually when people make their own policy, it’s in their own best interest, and because people trust what they know irrationally. So, can you convince people that matter that your solution is as good or better as an official IRB and deserves as much or more trust? Is the difference between your solution and an IRB less than the extra convincing?

My general suggestion is to first solve the problem rationally, and then have smart people justify your solution with the IRB official procedures. That’s because trying to follow any government document to solve anything without already knowing what you’re trying to do is a good way to make something asinine.

2) Opting Out

Problem: How can people leave the system?

If people cannot terminate their inclusion in an ongoing medical study, then what incentives keep that study to perpetually act in the best interest of its members, and what recourse do members have if disapprove of the company?

Note this except from the 23andMe Terms of Service:

Your saliva, once submitted to and analyzed by us, becomes our property. Any genetic information derived from your saliva remains your information. We retain the rights set forth in the consent form and any additional terms of service.

and from the Consent Agreement:

You have the right to delete your genetic information from our systems. Within thirty (30) days of receiving your written request, we will delete your account, and your information will not be included in any future research, including future research by other organizations. Any research conducted prior to the end of the thirty (30) day period following receipt of your request will not be altered or halted. Once your account is deleted it will not be retrievable.

Once information is shared with research partners, we cannot guarantee that it will be destroyed upon request.

Who cares about the saliva sample? It’s a legal convenience and standard procedure that physical objects you mail to a company become property of that company. What’s important is the genomic information is deleted to the best of their power on request, and that is contractually promised.

But clearly, there is confusion that’s making a problem, because:

1. If Steve was upset, and he’s a medical doctor of genetics and a smart, informed, active participant in the medical genomics community, then it’s not obvious enough that people can leave the system.
2. Keeping the saliva sample violates medical research conventions, and that offends the ethical standards of others in the medical research community.

Question: If a participant no longer wants to participate in a DTC genomic service, for personal reasons or as protest, what recourse do they have?

Existing Policy: Destroy the biological sample (the saliva) and the data on request. There’s probably some byzantine government policy to do this that Steve would know about, but I don’t care to look up.

Solution: Add account deletion to the main FAQ and promise to destroy the saliva sample on account termination.

First, know who this solution is meant to appease: the existing medical research and genomic medicine establishment. If it helps, think of them as old grouchy prigs sitting in ivory towers, and when something procedural is awry— regardless of its superficiality —their buttholes get very tight and they are unable to say nice things about your service. You don’t want to do that to the elderly, do you?

The addition to the FAQ is easy. Even better, add links to anchors to the relevant excepts in the consent form and terms of service in the FAQ text. As a bonus, this should help comfort customers, too.

I’m not suggesting anything else besides a promise to destroy the sample. It can still be your property, and you don’t have to implement any official policy. You can do that later. But in the meantime, this is an easy win that helps your image in the medical research community.

Redux

Predictably, 23andMe is crushing its competitors in everything information: software, marketing, web product, because that’s its founding background. Likewise, Coriell is crushing its competitors in everything medical research: policy, ethics, funding, because that’s its founding background. Specifically, everybody knows about 23andMe and their website and PR is excellent, but Coriell provides free, medical testing. Yes, it’s not “for education and research” like 23andMe. It’s a certified medical test. But, hardly anyone knows about Coriell, and their web service and marketing ranges from “non-existent” to “sucks.”

Imagine if West Coast 23andMe and East Coast Coriell joined forces…

But Drew, what about deCODEme?

Oh, they are for American’s, too. Check this out:

Can you get any more maverick American business cowboy than that? No.

Confusion about g2019s, LRRK2, and Parkinson’s Disease still circulates after the vacuous media blitz about Sergey’s blog. Here’s an except of a conversation from the 23andMe private member forums.

Not included is Paul Wick’s note: “I guess the only question in my mind for 23andMe from a regulatory perspective is at what point this is diagnostic vs educational; I know it’s a different kettle of legal fish in the latter case. ”

Indeed. However, g2019s is not used to make nor confirm clinical diagnosis of Parkinson’s Disease, so I think this still counts as “education.” (I so hate that word.) Personally? Assuming 23andMe makes the appropriate medical care available, I’d love to see them report diagnostic mutations.

PaulWicks asks:
LRRK2 mutations?

A patient with Parkinson’s Disease (PD) posted today on the PD board of PatientsLikeMe that Google founder Sergey Brin has tested positive for LRRK2, a mutation that is implicated in some cases of inherited PD. See the original blog here: http://too.blogspot.­com/­When I look at my raw data I can see some listings next to LRRK2 but I need some more help to interpret that data; how can I tell what is / isn’t pathogenic?

Cheers
Paul Wicks
R&D Director @ PatientsLikeMe.com

Andrew Yates responds:
LRRK2 mutations?

Hey Paul,

First, see http://www.helixgene­.org/press/g2019s­ for a simple fast-fact press release about the g2019s mutation and Parkinson’s Disease.

“tested positive for LRRK2″ is a misnomer, what you mean is “tested positive for a variation of LRRK2.” The distinction is important, bare with me:

LRRK2 is a gene that everybody has. Everybody would test positive for LRRK2.

Actually, the test is for a single SNP^[1] in the gene LRRK2 called g2019s. I see you’re R&D;, so in computer code, the test evaluates:

if (YourGenome[39020469][0] == A
       || YourGenome[39020469][1] == A)

What does this mean? LRRK2 describes the protein “dardarin.” Think of a protein as a string of amino acids. This “bit flip” in your DNA changes the amino acid glycine at position 2019 to amino acid serine in dardarin. As code, this is like:

if (YourGenome[39020469][0] == A
       || YourGenome[39020469][1] == A) then
    dardarin[2019] = serine
else
    dardarin[2019] = glycine
endif

Note: g2019s is an abbreviation for “replace (g)lycine @ position 2019 with (s)erine”

What does THIS mean? It’s thought that g2019s mutated dardarin increases the protein MAPK’s activity, and this gain of function mutation leads to neuron death. That’s why g2019s is autosomal dominant: you only need one copy of the mutation to increase function and to create a toxic effect.^[2]

This is only a test for one very specific change in LRRK2. There are at least 30 known SNPs leading to 20 known amino acid substitutions mutations for LRRK2, though most of these have not been as well studied or are as medically relevant as g2019s. But a mutation can be be anywhere on the gene and cause all sorts of subtle and complex effects depending on other proteins and the environment…

Editorial

So, as you can see, this is a very complex system with many minutia that aren’t well understood. While I thought Sergey’s post was quite good, it’s _extremely irritating_ to see this sloppily reported in the media (like the NYTs) leading to significant medical misinformation at worst and general confusion at best. This is complex and important medical information, and if a NYT tech reporter^[3] with a comp sci degree from Stanford completely bungles elementary bayesian reporting because he copy-pasted the first percentage out of a press release and link cited a blog so he could go home early for the weekend… then we have a lot of work to do. Why not just read “MSN Health’s “Top Ten Mutations That Could Change Your Life?” Enraging.

I can tell you that the genomic medical community is PISSED, and it’s not even 23andMe’s fault. As far as I can tell, 23andMe’s g2019s test and report are very good. But, the medical community only knows what they’ve read in the NYTs because they don’t have 23andMe accounts. All they know is “Holy Crap! the NYTs says that 23andMe says that you could have an up to an 80% risk of Parkinson’s disease! Those huckster criminals!” Clearly, that’s not what 23andMe or Sergey’s “Too” actually says, but that’s the cost of standard of media reporting about genomics today.

[1] SNP, or single nucleotide polymorphism. “single nucleotide” means one DNA letter is changed, and “polymorphism” means a known variant that’s found in at least 1% of a population.

[2] It’s thought that this mutation makes dardarin more active because serine can be phosphorylated and glycine can’t be, and this helps the dardarin change shape such that ATP can better access its active site. Dardarin adds phosphate to other proteins including the protein MAPK, and this in turn makes MAPK too active. This is not my expertise, so any corrections or elaborations are welcome.

[3] Miguel Helft and his editor, Damon Darlin

Our friendly government lists some available genetic tests: these are the real deal, high penetrance tests for things you already have or conditions you will get.

Unlike Sergey Brin, I don’t particularly care about a mutation that gives me a slightly increased risk for a disease. That’s not significant, though if the placebo effect of a 23andMe test gets you to exercise more, congratulations.

However, if I knew I was bound to get Huntington’s Disease, I would really live my life differently with the moral superiority provided by knowing that my time on this earth was sadly limited by my genetics. I would just take things so much more seriously than all those suckers blissfully unaware of the cold, cruel nature of reality.

For now, it’s prohibitively expensive to get every single genetic test. With how much I would have to spend today to get 50 patented tests I would be better off waiting a year and getting my genome sequenced, then analyzing the data myself to (illegally?) check for every high penetrance mutation.

Sergey Brin’s New Blog: “too” (discuss at Hacker News)

…

In 2004, my wife, Anne, introduced me to her future cofounders in 23andMe as they were studying the genetics of Parkinson’s Disease. As with my mother’s fear, I was skeptical about the study. I reasoned that if there was much to be learned about Parkinson’s in the genome, there would have to be a high percentage of inherited cases. In fact, I appeared to be right in that this particular study did not bear immediate fruit.

…

As a customer of 23andMe, I have always been excited about the product. I have found what pieces of DNA I share with various relatives. I checked whether other Brins were related. I explored my various gene journals — learning, for instance, that I have one copy of the fast twitch muscle fiber. I also looked over the health related entries and found that my genetic risk for most diseases is modestly lower than average but for a few diseases it is modestly higher.