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

Editor’s note: this is the 500th ThinkGene.com post, hurray!

It’s amazing how the cells look like conscious organisms chasing one another. Organisms on any level that are effectively predator and prey behave the same, be they single cells, insects, or animals.

Update: At least deCODEme features happy customers.

We here at Think Gene are still waiting for a report of least one person who will vouch as a satisfied Navigenics customer. To qualify:

• You paid full price for the Navigenics service.
• You are willing to vouch as a “satisfied” customer of Navigenics over the Internet using your full name and email address. (in lieu of a full name, we will accept a web domain)
• You are not an employee of Navigenics nor have any affiliation with Navigenics or its employees.
• You are not a member of the press. (blogs are OK)

There is no prize for identifying oneself as this happy Navigenics customer because we feel that the joy of being a happy customer of Navigenics would be its own reward.

A running tally of identified satisfied Navigenics customers will be kept below for your convenience:

Identified Satisfied Navigenics Customers: 0

Leave reports in the comments.

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.

On our “Why The Data Sale Story is Silly” story last week, Dr. Steven Murphy (the Gene Sherpa) of the genomics medical special practice Helix Health posted this video in the comments:

Steve:

This is a must watch fellas…

“Google’s Master Plan”

my response…

Andrew:

Steve, please don’t, “The Master Plan” is well-polished crap. What is Google doing that this video claims is so bad? Oh no, the announcer said “don’t be evil” with suggestive intonation? Oh no, they used currency symbols in the names of the founders? Oh no, let’s sacrifice a goat and purge away this great evil!

So what if Google is getting into health care? Give me one concrete fact why Google in health would make my life objectively worse. Show me evidence of this impending Google malice that threatens me personally.

What, because of “privacy?” That’s a nonsense word like “patriotism” or “democratic.” Yes, it would be wrong if somebody didn’t treat me for cancer because they knew I had cancer. But isn’t that the fault of the health care establishment, you know, the system that doesn’t treat what it knows about, and not the service that tries to learn what about me can be improved?

Just repeat that to yourself again: “Yes, it would be wrong if somebody didn’t treat me for cancer because they knew I had cancer.” Isn’t that just insane? Yet, that’s exactly how health care works today.

Give me one good reason why I should defend the status quo of health care. Because it’s foolishly funded by risk ignorance, and its only impetus is health emergency? What crap. Instead of me paying to pumping crones full of drugs for two more years of semiconscious Jerry Springer, how about I get health care that improve the lives of young people like me who already seem healthy today? I can see Google providing services like that in exchange for referring my health profile to, for example, drug companies. Fine. Great.

And… this is bad… because I’m only supposed to buy health care that I don’t think I’ll use to fix diseases that I could prevent?

Yes, I find insipid marketing blather like “democratizing” insulting to my intelligence, but “annoying” isn’t “wrong.”

But, as far as I can tell, my life has only gotten much better thanks to Google and its satellite projects. Does that mean that Google as a company is rewarded, too? Yes… and? So? Good for them.

Dr. Steven Murphy responds: (edit: are you really accusing somebody of a federal crime using a Valleywag report, Steve?)

“So what if Google is getting into health care? Give me one concrete fact why Google in health would make my life objectively worse.”

2 words Dean Ornish…..Dean is their medical advisor and what’s his answer to better health? “More Love” Bullshit…here’s an answer……pay freakin primary care doctors twice what they are getting paid now to see half as many patients….I don’t see google doing that…

“Show me evidence of this impending Google malice that threatens me personally.”
http://www.google.com/health_hipaa.html
Not HIPAA compliant my friend…why does everyone think that sales of this information will be to the benign Pharma companies…..There are several F’in bigger fish that want that data

1.)MetLife
2.)The Hartford
3.)Any bank thinking of loaning you money

Give me a break Drew. This play has nothing to do with healthcare and everything to do with discrimination…..Think a FICO score is a big deal imagine your banker knowing you are predisposed to heart attacks when you try to take out that mortgage….Come on, you have to see that as a serious possibility, especially know that they have an algorithm to re-identify de-indentified DNA samples….

http://valleywag.com/5025875/google-cofounder-funnels-money-to-wifes-startup-through-michael-j-fox-charity

“But isn’t that the fault of the health care establishment, you know, the system that doesn’t treat what it knows about, and not the service that tries to learn what about me can be improved?”

I agree the system is broken, but tests that aren’t evene scientifically or medically validated are not the way to fix this problem….How does a SNP scan give you better health Drew. I challenge you on that one. How will a SNP scan be used for better research without accompanying medical data like Coriell???

“Give me one good reason why I should defend the status quo of health care.”

I never asked you too.

“it’s foolishly funded by risk ignorance, and its only impetus is health emergency? What crap. Instead of me paying to pumping crones full of drugs for two more years of semiconscious Jerry Springer, how about I get health care that improve the lives of young people like me who already seem healthy today?”

I agree…we should stop treating people who have a negative life expectancy based on family history……And all patients should have to pay out of pocket for ICU care if they have a terminal illness….That will fix the system. NOT SNP scans and google searches….

“I can see Google providing services like that in exchange for referring my health profile to, for example, drug companies. Fine. Great.”

It’s not the drug companies I care about Drew….it is the financial institutions that set our credit rating and determine our borrowing capacity. You have to see that as a real possibility.

BTW, if you want to get people signing up for these scans all you have to do is give them Google stock for taking the test…..

“But, as far as I can tell, my life has only gotten much better thanks to Google and its satellite projects.”

Ahhh yes…….they have done great things in IT, Advertising, Economics, Education. But, unless they want to spend their money on primary care doctors and preventative care delivery rather than collecting bullshit SNP data they will NEVER do anything great with healthcare…Sorry

-Steve

I (Andrew) respond:

Steve: First and foremost, nothing said refutes my primary claim that the “Google’s Master Plan” video is all insinuation and no substance. You and I have created that substance, and credit for this discussion is ours —not this well-published but shallow propaganda internet video.

I have said that SNP data 23andMe sells now is mostly frivolous, and until it’s actionable medical information (which it is not yet), it will continue to be so. Partly, that’s because of the “gene patents” you lambasted today keep the most important tests out of SNP chips, and partly, that’s because doctors cannot professionally trust tests not that do not explicitly produce medical information. But mostly, it’s a new technology in the highly-regulated industry of medicine. It will improve, and patents will expire. It’s this idea of SNP scans I like: informatics to human biology.

And I have been one of the first to champion efforts like Coriell Personalized Medicine Collaborative. In fact, the findings released by studies like this will greatly benefit all genomic industry stakeholders, including 23andMe.

Me: “So what if Google is getting into health care? Give me one concrete fact why Google in health would make my life objectively worse.”

Steve: “2 words Dean Ornish…..Dean is their medical adviser and what’s his answer to better health? “More Love” Bullshit…here’s an answer……pay freakin primary care doctors twice what they are getting paid now to see half as many patients….I don’t see google doing that…”

Statements like “Caffeine’s effect on the central nervous system interferes with the mind body connection and therefore meditation and relaxation…” does ping my bullshit meter. Does Dean mean, “caffeine is a stimulant, avoid it to relax?” Ok, avoid stimulants to relax. But, some MD newage froo-froo on some board does not make my life objectively worse in any obvious way in which I can readily discern. (and his message of “live healthier by not eating trash and exercise” is OK with me)

As for the futures of doctors, I have bad news, Steve. Health care is seen as much too expensive in the USA. Pretend we cut costs by 50% for the same standard of care. Where in that equation do doctors get paid twice as much to see half as many patients? WHO is going to pay doctors more? On average, for the foreseeable future, the median pay of doctors will only go down.

Steve: “How does SNP scan give you better health Drew?”

OK: Test X requested in your medical practice has been placed on a SNP scan with sufficient scientific confidence. Does do your services at Helix Health give me “better health?”

Steve: “How will a SNP scan be used for better research without accompanying medical data like Coriell?”

SNP scans will add the clinical verification and standards of best practice produced and vetted by Coriell with that accompanying medical data.

Steve: “But, unless they want to spend their money on primary care doctors and preventative care delivery…”

They are spending their money to create software that abstracts away the bureaucratic waste of the health care industry and the expertise of physicians. That is because software is Google’s expertise.

Steve: “This play has nothing to do with healthcare and everything to do with discrimination…..Think a FICO score is a big deal imagine your banker knowing you are predisposed to heart attacks”

I don’t see “we will share your information with banks” in Google Health’s user agreement, and why should I trust HIPAA and the US government more than Google? From what I read here, Google’s policy seems to be even more private than what’s required by HIPAA. My assumption is that Google decided that compliance with HIPAA would be expensive, unnecessarily pedantic, and an tool to be used against them by a potentially hostile regulatory establishment, so they gave the entire act a big “F-U” and wrote their own policy.

I don’t know what Dr. Murphy’s problem with Google/23andMe is other than some irrational fear about “being tracked like cattle” and “having your genome, which now belongs to 23andMe, can now sold to lenders, just wait until you try to get a mortgage, Drew.” 23andMe is Citizen Kane-esque adventure in business, and it’s pushing the genomic industry faster than what’s probably comfortable for the existing medical establishment. Take it for what it is.

Hey, when 23andMe posts a stock photo of some model wearing a stethoscope on their homepage and plays Internet Doctor, I will stomp them, too. But until then, I don’t understand why some company selling some expensive, hobbyist “Apple I of genomics” is of any significant concern to a professional medical specialist of genomics like Dr. Steven Murphy. Steve, let 23andMe have their “spit parties.” You are a medical professional. You don’t need to address their silliness.