Solve this simple math question.

Statistics and disease risks are invented for this exercise!

1% of people will have Hubbub Disease by age 70. Up to 80% of people with Disease will get positive HEBOT mutation tests.  9.6% of people without Hubbub Disease will also get positive HEBOT mutation tests.  A patient had a positive HEBOT mutation test in genomic screening.  What is the probability that patient will have Hubbub Disease by age 70?

The correct answer is about 68.1%. If you got this, good job, you’re qualified, click here.

If you got a different answer or need an explanation, click here.

note: updated to be even more nonsensical to avoid confusion. Thanks, neandrothal.

I feel rationally obligated to distrust anything self-promoted as “Web 2.0″ in the same way I distrust statistics tacked with some vague quality like “40% more kick!” It’s as if those tacks are nailed right in to the body of Science itself, and I feel its pain. I feel it. Nonetheless, as I can be trusted to regularly grease the world economy $3.29 USD every late night caffeine sortie at the 7/11 across the street, there’s nothing physically impairing me from both believing that savant-like super powers wrought at the heights of all human achievement will give me more energy and help my money work for me while simultaneously loathing the idiocy that same electric blue sans-serif salespitch will sap my attention and wallet if only they could brand their goods with some impressive looking number. You know, like science and stuff. It’s as if behind the decimal point lies a secret realm where mere digits morph into runes of ancient magic, drawing the true, terrible power of tenth decimal place into a furious ball of psychogenic witchcraft burned by marketers into every web service and sugary softdrink for their duplicitous intent of short-circuiting my brain —not impairing rational thought itself, merely its ability to keep my money in my pocket and my faith to myself. It’s a near optimal function to illicit self-disgust.

Hey, I have an idea for a radical new financial instrument, it’s called: the hundredth decimal place. With marketing that tight, I may as well be selling soma to cashiers, right? It’s a brave new world out here on the interwebs, and I’ve got the confidence interval for you right anterior to my magic symbol “%.”

What was I talking about? Oh right.

Bertalan Meskó of Science Roll has officially launched Webicina, a service that sells education material and consulting to doctors about using the Internet and helps them launch a website. Regarding doctor blogs: Dr. Steven Murphy said today about his doctor blog, Gene Sherpas: “all they good things that happened to me this year have come from my blog.” Webicina is a valuable service that I endorse that will help your professional career as a medical professional —and it’s fun, too.

Here’s a funny picture of a dancing little boy wearing decimal point on his shirt. I want you think of it every time somebody uses a decimal point or any other statistic without justifying their significant digits or measurement confidence.

PS: I never want to see the expression “Web 2.0″ ever again, and God help you if I see anybody try to peddle *shutter* “Web 3.0.” To a lesser extent, that goes for that “59.5%” penetrance estimate for g2019s LRRK2 report at 23andMe, too.

You sometimes add a new dimension to blog-ramblings Andrew :-)

Here’s why you need a genetic counselor: http://tinyurl.com/4ccbo6
- and here’s why you might not need one: http://tinyurl.com/4a9ytg

Originally posted as a comment by Sciphu on Think Gene using Disqus.

Story: genetic councilors are people you pay to console you about the results of a genetic test report to make you feel better and help you make rational decisions about your health when your reasoning may be distorted by emotional distress. If that’s a service you want, buy a couple hours from a genetic councilor.

Computers can never provide human consolation, no matter how excellent and rational their reports. Doctors and scientists feel that councilor work is beneath them, nor are they typically any good at it, nor do they realistically have the capacity to do it. However, scientists tend to be much better at analyzing complex information, and medical doctors can use reports to better synthesize a general understanding of your health to recommend medical action not already prescribed by obvious standard practice.

For example, I would probably make an excellent systems biologist, but the world’s worst genetic councilor. “Beep-bop-boop, you have Huntington’s. Don’t have children.” See? A that’s perfectly rational statement, but it’s illustrative why genetic councilors are important.

But how many people in health care today can read the following expression? Or write it? Or tell me what it means not just clinically, but biologically?

re.search('(CAG){36,}',genome[4][3046205:3215485])

Steve at Gene Sherpas reports systemic medical insurance fraud in many top institutions providing genetic health care. Clinics are billing as if doctors are seeing patients, but only genetic councilors ever see the patient. “But I have a solution,” Steve exclaims. “The answer: Nurse Geneticists.” He continues, “Call your insurer. Demand to be seen by a physician or physician extender… Why should you demand this service? It will put stress on the broken system. To repair that system, we must first rebuild the foundation.”

Be careful what you wish for, Steve. Systemic abuses like this that risk high liability for meager reimbursements suggest a deeper problem than petty greed. Either the system has collectively concluded that genetic councilors are sufficient to perform the service and that they are following procedure “in spirit,” or they are desperate to keep unsustainably high margins and must resort to abuse to protect them. I suspect some of both.

The problem genetic councilors is political. Genetics used to be called “eugenics,” literally, “the science of the well born.” After World War 2 and the civil rights movement, it became taboo to socially direct population growth and the practice of human genetics was legally and institutionally castrated. Today’s “non-directive” genetic councilors are the progeny of this purposefully impotent profession.

However, scientific progressed. We discovered DNA. We learned molecular biology. We sequenced the human genome. Suddenly, the members of this small, marginalized profession were both keepers of the hereditary taboo and keepers of the code of life.

So, that’s what genetic councilors are: specialized nurses who aren’t supposed to touch you or tell you to do anything, but who have become the hands, eyes, voices, and smiles of this newest, most vital paradigm of medicine. So long as people need a warm consult and an authoritative opinion, there will be a place for you.

That’s probably the nicest thing I’ve ever said on this website.

Old medicine was dead the day you adopted “evidence-based medicine.”

There, I feel better.

What medicine? Scientific medicine. Mathematical medicine. Mechanized medicine. Terabytes of cited hyper-linked studies compiled into statistically weighted results medicine. Input symptoms and test results, output diagnosis and CPT medical billing code medicine.

Beep-bop-boop you’re dead, have a nice day. (the industry, the not patient, who of this ethnicity and phenotypic profile can expect 55.2% efficacy and 82.1% efficiency over control who received traditional care)

And no other medicinal discipline is as scientific mechanical as genetics. How mechanized? Watch, I’ll make a free clinical diagnosis machine prototype right here on my blog. Yes, not a risk report, a real diagnosis. Just input your genome sequence service account login, and my machine download your genome securely from your sequence service and practice medicine.

Your Sequence Account OpenID URL:

Your Password:

#!/usr/bin/env python
import genome
HTT = genome.autosome[4][3046205:3215485]
if genome.search('(CAG){27,35}', HTT)):
    print "mutable"
elif genome.search('(CAG){36,40}', HTT)):
    print "reduced penetrance"
elif genome.search('(CAG){41,}', HTT)):
    print "positive"
else:
    print "negative"

Would you like to subscribe to our genetic counseling service? Now, only $89.95 a month!
Don’t have a sequence? Sequence with us! Now only $999.
Enter your credit card and you gmail account and password below.

The real question is: are you dead like “mama bell” AT&T, the century-old institution that suddenly crumbled and consolidated. Or, are you dead like the newspaper, a slow and humiliating decline of consolation and standards of with only a few prestigious survivors?

So, OK, some genetic councilors will go back to school for additional nursing or physician assistant credentials, and some genetic centers may begin staffing appropriately if they can afford to despite the gross waste in health care already. But realistically, I’m supposed to believe that genetically-trained nurses are the solution? A new, more expensive kind of medical profession for which academic and institutional support will take decades to mature? When America is straining under grossly inflated health care costs during an economic depression? Meanwhile, I can hypothetically write a Python script to practice medicine and hire a perky and well-educated Indian genetic councilor to answer phones now for cheap?

Have fun breaking the system, Dr. Murphy. It needs to be broken, sure, but I’ll meet you down here at the bottom.

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 some medical research convention, 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

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.