You can't have it both way. Either scared your genome is sold off or not.

I recently read a Times blog post by Mark Henderson because it was referenced by Dan Vorhaus on Twitter. I have to say, I am blown away by the cognitive dissonance here......

entitled " The end of deCODE genetics: are you worried about who holds your DNA?" I was interested in to see whether this was a slash job on deCode or not.....

"Does this worry me? Not really. First of all, as Dr Stefansson pointed out to me yesterday, deCODE was a publicly traded company, listed on the NASDAQ. It was always up for sale, and in a manner of speaking its ownership was changing all the time."

Is he serious? Minor shareholders having access to a company's intellectual property and a hostile board takeover? That is what it would have taken to get the control.....or bankruptcy. Which is yet again another reason why a doctor would be able to protect this data better than a corporation.

Will there be any more doozies in this?

What I found was a hard pill for most to swallow. The end conclusion:

"What's more, though, I've yet to be convinced that there is anything particularly sensitive about an individual's genetic information. For the moment, at least, the sort of genotype data held by deCODEme isn't very useful to anybody other than me -- and even then, its chief value lies in satisfying my curiosity. I'd be much more worried if it was my financial data that was changing hands"

Ok, so here is the problem. Either you believe or you don't believe that your genome will hold useful information that may help predict your risk for disease.

If you do believe, then how could you not be scared about some discovery down the road that may be used against you by the "new owners" of your data?

If you don't believe it is a big deal, then why in the hell did you have the scan in the first place? To write a "news" story? Sorry, I mean PR piece......

In fact that's it. The people who bought these DTC tests were SV tech junkies and piss poor journalists who couldn't get anything else published. Now that they have all used up the story, there is no one left to buy decodeme.......et.al.

I do agree with the writer on one thing: There will be more failures. No amount of PR can fix that.

The Sherpa Says: Either you believe or you don't. For those who do, DeCode's failure should shake you. I am certainly glad I chose the IRB approved Coriell Personalized Medicine Collaborative to do my SNP scan.......

Hey DTC genomics, Stay Private, Stay Alive, Go Public and Die

Today's lesson in start up business in the field of DTC Genomics is this.....

Stay Private and Stay Alive. IPO and doom yourself to a painful and public death.

Huh? Ah, yes our first DTC Genomics venture is going to be restructured to someone else and the thought experiment will become a reality.

"When a DTC Genomics bust, what happens to the data?"

Well, someone else can buy it, at a rock bottom price. Hell, the selling company can even violate YOUR TERMS OF AGREEMENT!

Daniel, posts a great email from some sucker who bought DeCodeMe......or maybe just an "Early Adopter"

" there has also been filed with the court an offer by Saga Investments LLC to purchase deCODE's Icelandic subsidiary, Islensk Erfdagreining (IE). IE, which is not declaring bankruptcy, carries out all of deCODE's human genetics work and and provides deCODEme."

So, Saga Investments, a private firm will be taking over in Iceland and likely will be handed the keys to a bunch of genotypes.....

"For this reason, we do not expect this to have any impact on your deCODEme account. As ever, our commitment at deCODEme is to keep you in the forefront of progress in understanding the human genome and what it means for you and your health."

What did this achieve? Well, it took the DTC DeCodeme out of the publicly owned realm. Which is probably a good thing. Let me tell you why.

Publicly owned companies shares are extremely liquid and can be crushed pretty easily, where as rich ol' moneybags (SergeandMe) can keep throwing money into the kitty and outlast this economic downturn and premature launch of these companies, hoping to innovate his way out of this money pit.

This reason is probably why DeCodeme went private and will likely give up control of their data. They need some sucker to keep pouring money into a boondoggle that has no exit for at LEAST the next 15 years if at all.

The moral of the story for start ups is "Stay Private, Lose Investor's Money, Live, Innovate (gulp)"

The Sherpa Says: Now I want to know how many people will file a class action against DeCode for selling the data? Any ideas? Because that could really make the genetic data an unwanted commodity.

Stop. Breathe. Repeat. An analysis of the direction of DTC Genomics Field.

I have been railing the last few days so I want to take a step back and examine what exactly is happening in the DTC Genomics space. (By no means an exhaustive list)

Navigenics-Partnering with a concierge medicine group of Internal Medicine physicians, convincing them to use an unvalidated genome scan to practice predictive medicine. Also using clinical language and inferring that this service can be used as such. Also with the new CEO who used to be a muckety muck at Humana Insurance company.........Hmmmmm, add in the PR hype of partnering with Harvard to Educate the pathology residents about microarray testing without the knowledge of Harvard's Clinical genetics teams.....and you have some pretty nefarious stuff going down here.....in the quiet light of day.

Pathway Genomics-Funded by the PayPal Mafia and the Napster Wunderkid split their services into clinical and ancestry. Smart.

23andME-Partnered with anyone they can get their hands on, recently split their service lines into ancestry or clinical OR both......They have had 2 rounds of layoffs, lost one of their founders, moved into the googleplex, have employees leaking info about them online, have cut software engineers and kept the PR/marketing people, pissed off the NYS attorney general and now changed prices AGAIN

TruGenetics-Couldn't find funding and are in holding pattern........who knows what that means. But they did prompt a brief legal review of what would happen if one of the DTC companies goes bankrupt or is sold......Basically, all bets are off and your data will likely be sold off without your consent.

Knome-George Church's vanity plate is still alive and kicking. Partnering with SeqWright and Beijing they are positioned to take care of the rest of the worlds billionaires.......until the price of genome analysis comes plummeting down........

Scientific Match-Still making matches one MHC group at a time.....luckily they don't test for medical conditions.....

DNADirect-Wow! Has Ryan managed to drive under this radar! I am so amazed at what DAN Direct has morphed into. They are in essence a medical practice who also directly competes with generation health on the GBM side. They are also serving as a telegenetics consultation service. In all honesty, DNADirect is the true bellwether here. They have been around since 2004 and have weathered all the shitstorms. Which means, many other companies are likely to follow suit, in a matter of years and at a matter of costs.

DeCode-What was their stock price again???

DNADynasty-Enough Said


There are others, but I think this is a good list to review and think about where they are in the life cycle of direct to consumer genetic testing.

The most interesting of these is DNA Direct. Ryan Phelan started out with a message of:

"You deserve direct access to your genes"

Then became, "We partner with doctors to give you the best care of your genes"

Now is that PLUS, "We help your insurer save money by directing how you pay for your genes"

What has occurred? Well, they saw the law, they also saw that they couldn't survive with just computer science engineers or marketing and PR folk.

Ryan saw that the real growth potential is in caring for people. Why is that important? Because genomic medicine is about medicine and people. Not stock photos and flashy websites.

She is right. I am always amazed by her prescience here. Despite my wailing about here over the years, she has come around to my side....

Will the other companies follow suit? One thing is for sure, Ryan isn't around just because she has raised lots of capital....

The Sherpa Says: I have been here climbing the personalized medicine mountain for a while now. I have seen 'em come and go, but Ryan is a seasoned climber. More of these companies would do better pay attention to her rather than silly price changes....

An argument 23andSerge can't win...23andme but not medicine

"As I had postulated before, in order to move towards a profitable direction the DTC companies would have to choose "Medically Relevant" or "Novelty Testing" From this recent email sent to me by a reader it is clear, 23andME is Choosing to become a clinical service, without accepting the clinical responsibility."

This from my post February 14 2009

That was the day the announced that they were doing BRCA testing. Since then we have created a little video that may now be running through the silicon valley.........

Why?

Because, at the Spittoon (brrrrrrr-ding) they have announced that they will be splitting their service into 2 different types of tests

The first "A Novelty Test" which will be solely for ancestry.
23andMe Ancestry Edition – $399

The second "A health test" which will be solely for medicine while still disclaiming it is not. 23andMe Health Edition – $429

"With the launch of the 23andMe Health Edition we are releasing 13 new carrier status reports. These reports will help you know more about what may be in store for the next generation. We are expanding our cystic fibrosis panel report to cover the full panel of mutations recommended by the American College of Medical Genetics, as well as several additional mutations. We will also be providing data for most of the mutations routinely screened for in the Ashkenazi Jewish population, including those associated with Tay-Sachs disease, Canavan disease and Bloom’s syndrome.

We are also continuing to expand our drug response offerings. The next report to come out, Pseudocholinesterase Deficiency, contains information for anyone who will be undergoing surgery."

Ok, a couple of things.

First-This health test IS a MEDICAL test. I have sent off CF carrier screening medically, I have also sent off for Malignant Hyperthermia testing as well.........

Each has their own limitations which I have had to counsel patients about........For an hour a piece.

Second and more importantly, this appears to be another price change for the 23andME service.

If it turns out this company gets eaten up by Google, I am certain google will then own your genome scan data.....So I have one thing to say to the consumer

"If you want google to own your genome data, then by all means buy a 23andMe test"

Buyer beware here, please. I only ask and beg the proper authorities to uphold the current laws and regulate appropriately to protect the public health and welfare.

Why do I say this? Because a BRCA test or a CF carrier screen which was inappropriate that has been performed already on the public, without medical regulation, or without proper medical guidance could cause harm.

Lastly, this is likely a salvage play to keep the ancestry service before the feds come sweeping in......shut the medical service down.

I am certain.

Well, at least they (Feds and 23andSerge) have heard us........we only grow stronger because we are correct and hold to the theory that "What's Important IS What Is Important"

The Sherpa Says: Democratization is important, but so is not dying.......Why mix hair color with BRCA testing? I am glad Serge sees that too.......But now that leaves the health test as "Not for Fun" Looks like quite a change in defense of Mountain View's medical practice without doctors.....

Congratulations Generation Health. Nice pick up!

Is it any surprise that insurance companies have no clue what the hell is going on with genetic testing?



You see, there are a set of ICD9 codes that can mean 2C19 testing or hepatitis pcr........



The coding system doesn't allow the companies to run their algorithms accurately......



Insurers have no clue which is which and they are getting banged out for these tests.



Don't believe me, just take a look at what United has done with their BRCA testing (which BTW has their own codes)



"By instituting a prior notification policy and placing Myriad in charge of determining which patients get tested, United Healthcare can monitor more closely which of its policy holders are receiving testing on BRACAnalysis."



Add in the SGO guidelines which suggest a 5% BRCA carrier risk may be worthwhile and you can see why the companies are looking to stop the carnage or testing overuse.



Myriad on the other hand would beg to differ. They see years of under utilization as something to combat. And they are very successful at it, just check out MYGN.



The answer is somewhere in the middle. What is a responsible insurance company to do?



Answer: Generation Health.



What happens when genetic testing costs less than 100 bucks? Well, then maybe Generation Health will need to speak with me regarding a diversification company we are working on.....



With other PBM companies actively looking at new automated strategies for GBM (not glioblastoma multiforme) Generation Health is an interesting play.



I remember speaking with a certain player who also was involved with the DTC companies, who agreed with me. DTC is a bull$h!t play, benefits management of real testing, hyperlipids, HCM, etc are where the puck will be......From the Genome Web article (HT Turna Ray)



"The partnership will also “allow the companies to explore future programs in the medical diagnostics arena to encourage appropriate and cost-effective testing for certain hereditary diseases, and eliminate unnecessary testing where evidence for clinical validity and utility is lacking,” the collaboration partners said in a statement. "



We talked about this for some time (unnamed MD and myself) and then.....radio silence.......Only to show up with funding and some small hits.



They chose genetic counselors instead of my band of geneticists......



These guys are moving in the right direction. The industry is shaping up and guess what the killer app for genetic testing is?????



That's right, actual, honest, regulated medical testing........ Go figure.



Now, who gets what, how is it paid for, how is it used?



These are the questions that will need to be solved.



Until of course the accuracy and cost of a genome is less than 500 USD Which could be quite a while.



Meaning, Generation Health has about 10 years of life as the company it is right now. Not bad.



Imagine saving insurers millions per year, then taking 10-20% of those savings......... per year CVS/Caremark is a great partner and now owner/investor.........A very strategic investment.



My guess is that the DTC companies will fall in line or perish. Then labs will have to start marketing better, offer faster turnaround times and there will be "preferred" lab status.....per insurer.



Basically creating a super confusing land mine for physicians and patients. Just like radiology, just like surgery, just like chemo, just like......medicines



The Sherpa Says: Finally, corporations and investors are figuring out what IS important. Staying alive and having your medications work!!

Long QT Syndrome, location matters

I just saw a family who had Long QT with a KCNQ1 mutation ripping through them. Which is why I loved this email I received from one of my long time readers the day after I saw them.

Closer Look at Genetic Testing in Long-QT syndrome

One of my favorite lines from this paper was

"Nothing tests the tools of clinical risk prediction quite like sudden death."

Ummmm......Uh Huh.

They go on to say

"The difficulties encountered in the clinical application of genetic data, even in inherited conditions such as the long-QT syndrome (LQTS), in which the transmitted risk of sudden death is several hundred-fold greater than that in the general population, highlight some of the hurdles that must be overcome if DNA diagnosis is ever to transform cardiovascular medicine. "

The reader then went on to send me a release from ScienceDaily

But I should probably give you some background.

Long QT syndrome is a condition where the electrical activity in your heart is faulty. In fact, the conduction system has dangerous delays that can lead to dangerous heart rhythms which cause sudden death.

It is so serious that in every single patient I see, I ask "Has anyone in your family died suddenly or in their sleep? Has anyone had any crib death? Any sudden unexplainable car accidents?"

This is my lay screen for Sudden Cardiac Death (SCD).

Long QT is one of the causes of SCD. The rate is about 1 in 2000 or so. In 10% of people roughly, the first symptom is sudden death. This can be due to exertion, stress, auditory triggers.

A multicenter study was performed to evaluate genetic "noise" in 1400 controls and approximately 400 subjects (Far more than the Norovirus resistance gene for 22andSerge)

What did they find? They found some noise......of course.

This noise was present in about 4% of controls. This is surprisingly low in my estimate......

What else did they find? They found a genotype/phenotype correlation. Which in Autosomal Dominant disease is also no big surprise. Which likely will be augmented with modifier genes.

What is the "noise rate" for other genes? That, my friend is a good question.

What is noise? It could be anything we haven't classified as for certain pathogenic or benign. For BRCA we call these changes "Variants of Uncertain Significance" or affectionately known as VUSes

The VUS rate for BRCA is anywhere between 10 and 15 percent. Which is why I was so surprised about the LQTS study. Heck, there are more than 2 genes involved in LQTS

So why is this noise such a big deal? As we reach the precipitously dropping cost of the genome, we will be able to have a whole bunch of noise......

In fact, I think it will take us at least 20 years to sort out that noise. Add on layers of epigenetics and we may have another 20 years.......

Why so glum? We do have pretty valid clinical testing for Sudden Cardiac Death. It works, MOST of the time. Whole Genome Scanning?

Well, that may be a different story. I have harped on the Incidentalome several times on the blog, but this bears repeating.........

" If practitioners pursue these unexpected genomic findings without thought, there may be disastrous consequences. First, physicians will be overwhelmed by the complexity of pursuing unexpected genomic measurements. Second, patients will be subjected to unnecessary follow-up tests, causing additional morbidity. Third, the cost of genomic medicine will increase substantially with little benefit to patients or physicians (but with great financial benefits to the genomic testing industry), "

-Zak Kohane

"Mathematicians modeled sequencing the whole genome. As they get up to sequencing 10.000 people they find that the fraction of the population with a false positive result skyrockets up to 60%. What does this mean? Well, we have to carefully select who we test. Or better yet we need an immense database of "Normal Variants". At a minimum we will need 1000s of "sequence specialists" or "computer sequence analysis programs" to evaluate and decide if the "work up" is indicated or not. Personal Genomics is very complex, even more than personalized medicine."

-Steven Murphy in 2007

The Sherpa Says: In Genomics, there is going to be a whole lotta maybes........which in case you are curious, computers handle very poorly....

Good Enough Science? Apparently so at 23andme

"A total of 61 individuals involved in five norovirus outbreaks in Denmark were genotyped at nucleotides 428 and 571 of the FUT2 gene, determining secretor status, i.e., the presence of ABH antigens in secretions and on mucosa. A strong correlation (P 0.003) was found between the secretor phenotype and symptomatic disease, extending previous knowledge and confirming that nonsense mutations in the FUT2 gene provide protection against symptomatic norovirus (GGII.4) infections."

This from a report at 23andSerge's "Norovirus Resistance" report.

I don't know what I would do with a Norovirus resistance report........Go on more cruises? Work in a daycare? Have more kids?

I bring this up because I begin to wonder what level of science is good science.

Is highlighting every article as useful as highlighting important and valid articles?

It seems to me that the best thing these companies can do is focus on good things and play a role in dispelling the not so good studies.

Heck, this is something I wanted to do on the Sherpa, but lack the resources....i.e the 13 million to burn on curators. So I select only the most relevant studies for PM and review.

I wonder if they (DTC Genomics) are just pulling up every study possible or if they are actively curating the data.

Because if they are curating, I wonder who is at the helm.

These are the studies they chose for the Norovirus report

Le Pendu et al. (2006) . “Mendelian resistance to human norovirus infections.” Semin Immunol 18(6):375-86.

Lindesmith et al. (2003) . “Human susceptibility and resistance to Norwalk virus infection.” Nat Med 9(5):548-53.

Hutson et al. (2005) . “Norwalk virus infection associates with secretor status genotyped from sera.” J Med Virol 77(1):116-20.

Kindberg et al. (2007) . “Host genetic resistance to symptomatic norovirus (GGII.4) infections in Denmark.” J Clin Microbiol 45(8):2720-2.

Thorven et al. (2005) . “A homozygous nonsense mutation (428G-->A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections.” J Virol 79(24):15351-5.

Just from reading the abstracts not a single study had any number greater than 63 symptomatic patients.

Not a single study in my mind had statistical significance required for an association or a linkage study.

What in the hell is going on with the science?

If an apomediary is to be given free reign (Which I argue they should not in medicine), they better prove they are

1. An expert
2. Knowledgeable about the statistics required for the information presented
3. Not given false information, in science, non statistically valid information
4. Not a harm to the people they provide information to.

I think this is an example of a Big Fail here.

Yet they put it out from the rooftops, yelling on twitter, facebook, their blog, ALL OVER.

What in the hell is this information to be used for?

Even if for fun, it doesn't help if scientifically it is suspect. Isn't this what we bashed DNA Dynasty for? If this company wants to do right by people, they shouldn't boost the unimportant to the level of importance......

The biggest problem about this and other examples is the fact that the studies are not being vetted properly and the rushing to make a big deal out of suspect studies. This is analogous to the press publishing some crap study on the news. Which BTW, I have managed to tune out, because most of what they report is wrong. If they were a news organization, I would not be as pissed here, but they are not clearly just a reporting service, despite what SB 482 said.

23andSerge tests human biologic samples and gives diagnoses. As well as promotes unimpressive studies in an attempt to sell more tests......GREAT BIG FAIL!

The Sherpa Says: If this is the example of expert information that patients/customers can use to empower themselves, I would say they (Both 23andSerge and Customers) could do better reading the National Enquirer for health tips...

Change IS Needed. I agree with William, sometimes.

Over the past day or so I have been engaged with one of my fiercest critics. No a critic of me per se, but a critic of my opinions in the space of Personalized Medicine.

We may have a "truce", maybe......

William Gunn PhD is a pretty amazing guy and if you read his CV you can see he is very involved in the space and an excellent scientist.

Yesterday he and I exchanged emails and he posted a letter to the medical community. I think it is a great letter. He expresses some of the EXACT SAME frustration I have.

"I believe, as does pretty much everyone, that medicine is on the cusp of great changes and that personalized medicine holds great promise. I believe that an informed patient is an empowered patient, and ultimately a healthier one. Every good doctor should want this, and every below-average doctor should pray this day never comes."

I love his opening lines, but there are some problems that I see.

First let me state I agree with most of what he says, but:

1. There are a whole bunch of people who think personalized medicine is a pipe dream created while chilling with the caterpillar and Alice. Namely, doctors, scientists and politicians

2. I think most doctors try to help people, even the less than average ones. An empowered patent would be a benefit to them, but it depends on what the definition of empowered means.....

That is the major league difference between doctors and "super early adopters" in the DTC genomics space.

What is the difference?

The definition of empowered patient.

I have heard it described broadly such as

"Patient empowerment in the health care context means to promote autonomous self-regulation so that the individual’s potential for health and wellness is maximised."

This could be just about anything, including diagnosis and treatment. Which is interesting because in all states of the US you need a medical license to do that.

I also have heard it stated specifically in the Patients Bill of Rights as

"The providing of information regarding therapeutic options so that a Patient can actively participate in the decision on whether to undergo a diagnostic or therapeutic procedure, or pursue alternatives." See Patient Bill of Rights

This is obviously more specific and falls in the realm of, you have a disease, now you can be empowered to actively participate in the discussion. I have always thought that if you don't have the terminology of medicine, this part puts you as a one legged man at an ass kicking contest.

The ideal place for patient empowerment is not sick in the hospital, by that time it is too late. You are sick and not likely to be able to learn as well as if you were healthy.

Which is why the empowerment piece should come in at the doctor's office or even at home in your underwear on your MacBook. I agree. I love when patients come in having read stuff. Just recently a patient came in knowing just about everything about a familial disease....the consult was super awesome and we had a great discussion. But again, this was a motivated subject.

But I ask, is that what the DTC Genomics coummunity thinks empowerment is? Is empowerment education? That is what the health community thinks.

But, William et.al. think it is more than that. They think it is access to biometric data AND interpretation of that. In some aspects, this could be considered education......

I agree, it is education of a sort. When it is from your doctor it is called good medical care.

But often it is through an Apomediary.

What's an apomediary? Well, 23andME considers themselves such.
even I consider myself an apomediary in things for which I am not licensed for (golf, start ups, etc). I.E. a self defined expert providing guidance to information about their "expert subject"

But for medicine, I am a licensed, board certified physician who has worked long and hard to stand by my expertise (8 years of work after my undergraduate work). Unlike DTC genomics companies, who are neither regulated, nor accredited to give expert medical opinion.

Thus, they are apomediaries. Is patient empowerment, unregulated access to apomediaries? Well, maybe. But I argue that DTC genomics are more than just Apomediaries.

They test human biologic samples and provide a diagnostic result, despite stating they are not providing diagnosis. Think BRCA carrier status here. Which BTW is a medical diagnosis. With a medical test.

So, is patient empowerment the ability to obtain diagnoses from a non licensed diagnostician?

I would argue that this is precisely what I am opposed to. This can lead to all sorts of danger. Last time I checked, laudanum was not FDA approved, nor were the apothecaries.......

The Sherpa Says: We have come a long way since then and going back there would put us squarely into the stone ages for quality of care. Which is why I am so vehemently against a company that tests your human biologic sample and provides a diagnosis without being licensed to do so. Change is Needed William, I agree.

Away and now back, What did I miss???? 23andme layoffs? Selling Genomes for cheap up next!

23andSerge has layoffs, big surprise.

When Linda left, she had a tribe that left too. I am working on hiring one or 2 and will see what exactly was going on over there......Likely a huge cash bleed

GAPPNet has their first meeting, which I missed.

I will email Dr. Khoury and find out how it went.

Daniel MacArthur pointing out that 23andSerge could have bashed bad science, yet instead promoted it......No surprise there either.

It looks like 23andSerge fired the engineers and scientists.....and kept the PR and marketing wonks.......

Well, in the end it is crystal clear

It turns out the lawyers questioned this as well as Misha.....Turns out, if you took the genome, then you probably can sell it.......better yet, if you "acquired it via firesale" you also can probably sell it and break all kinds of "terms of service"

What's important? Not having your genome sold off? What's important? Being able to be certain the person who has your information won't sell it to the highest bidder......Now do you see why it is important to have a doctor involved in this? We CAN'T sell it off. Even if we wanted to. It would be against the law......10 years in Folsom or 250,000 USD......OR BOTH!

The main problem is that a lot of people are confusing things.

What is important IS "What is important" not cocktail parties, blimps or CEO's from insurance companies

(hmmm, I wonder what Navigenics is thinking about doing with it's company?) Maybe Humana wants Navi, to profile their patients?

The Sherpa Says: Companies are most dangerous to their customers and the public when the chips are down. They often do unthinkable and crazy things........for cheap. Anything to survive, that is the motto of the startup. Do or should they have any loyalty to you, AFTER they already have your money? No, unless legally bound.....This is yet another reason why a doctor should be involved here.