Thursday, May 28, 2009

Gina, the First Wave

The first wave of GINA now goes into effect. This part goes directly to affect Heath Insurers. To review the law signed in May 21 2008 will directly affect Health Insurance and Employers.

For this wave we are regulating Insurers in such a way that:

Health insurers may not require individuals to provide their genetic information or the genetic information of a family member to the insurer for eligibility, coverage, underwriting, or premium-setting decisions. However, a health insurer may request that an individual provide genetic information if coverage of a particular claim may be appropriate only if there is a known genetic risk. For additional information, please read the Q&A portion below, entitled "What about submitting claims to my health insurance company?";

Health insurers may not use genetic information either collected with intent, or incidentally, to make enrollment or coverage decisions;

Health insurers may not request or require that an individual or an individual's family member undergo a genetic test; and

In the Medicare supplemental policy and individual health insurance markets, genetic information cannot be used as a preexisting condition.
It will certainly be interesting to see how the attorneys react to these regulations.
I am fairly certain that it will end up being a good thing for patients and perhaps a difficult thing for most insurers...

The Sherpa Says: Congratulations to the United States Government for at least getting something right. Watch out employers, you come under scrutiny in November of 2009.

Wednesday, May 27, 2009

Bargain Basement Consumer Genomics Conference

Step right on up, come one come the greatest show on earth!

Demand is so high, that we've dropped the price 99%

That's right, the greatest show on earth, known as the Consumer Genomics Show has reduced its exorbitant cost, just like genome scanning is going to do!!!

From 850 USD, which was dropped from over 1000 USD, to now 8 dollars and 76 cents

Just use the special coupon code DNA123

Yes, that IS recessionary pricing at its best.

This Show has "Shown" me its true value.......A sandwich at Cosi......minus the fulfillment of that Chicken Pesto and less the substance....Ahhh, PT would be proud of thee.....

See you there suckers!

The Sherpa Says: What an unbelievable scam. I am blown away at what our profession has allowed the hucksters in business to get away with....perhaps we are too busy being scared of what President Obama will do to our profession that we have forgotten to see the bigger picture. Or maybe we are too busy fighting for tenure and grants??? Either way, they have the advantage.

Tuesday, May 26, 2009

Long Weekend, Lots to cover.

First, I want to thank reporter Devon Lash at the Stamford Advocate, who wrote a very nice piece about the CT State Dept. of Health asking seniors to speak up about diseases in their family. So many people didn't speak of these things just a few decades ago, but they need to. The article misstates what I said, which is nearly over 40% of women were reclassified when using the Reynolds Risk score in comparison with the Framingham. 

But I think you get the idea. Public Health Departments are now pushing Family Histories......NOT SNP SCANS..... 

Often I am presented with a patient who says "They never spoke about it". I tell that patient to go to their family member and "Make them speak about it" What they tell you may just save YOUR life.

I am glad we are not the only ones doing this.  

But in true push science to the public in an attempt to market it fashion, family history has fallen behind the big money push of SNP scans......despite evidence that family history outperforms SNP scans all the time.

A meta analysis was performed, yes I have complained about METa's ability to bring actually results and not just play statistics.....but this set of studies are in fairly homogenous populations.....still, I have some caution when reviewing these.....

It is true, Family History does have shortcomings and it is in the realm of often false assumptions that we make these mistakes.......

I see this all the time. Doctors have sent patients to us who say that they are at risk of Colon Cancer because of a BRCA family history.....Untrue....these are not really linked.....which is why I applaud the efforts in Canada to start linking patterns and noticing risks.....But even with a great cancer registry it turns out what may hold for BRCA may hold for most other hormonal cancers and colorectal cancer. A recent registry review which was analzed using log regression found little relation between, prostate, endometrial or ovarian and Colorectal Cancer. In addition, they saw a small (as in on the order of SNP scan) relation of Breast Cancer and Colorectal Cancer....

Why are there shortcomings here? Well for one, we know that Lynch syndrome has Colon, Ovarian and Endometrial..........This is a valid connection.......

For second, this is as is most family history data, retrospective. Which is not to say it isn't better than a GWAS scan which was only replicated once.....but it is not the most solid....

But while there are shortcomings, Family history still kicks SNP scans A$$ in when it comes to data and clinical studies.....

This is why every patient which walks through the doors of our offices gets a 3 generation family history......

Oh and the best part, it's essentially free to the consumer/patient......But alas, no big money has decided to put on events for Consumer Family History Shows.......

The Sherpa Says: All the money in the world can't create data that requires observation over time......even Pharma fails at doing this.....So why would any venture cap think that they could revolutionize medicine without putting family histories in their risk engines??? BTW, 800 USD is overpriced, just like the SNP scans........

Thursday, May 21, 2009

Swine Flu In Greewich CT!

Yes, Swine Flu again. It turns out that Swine Flu is now in our town of Greenwich CT. So I will put up a checklist here......Not that any Genome Readers would be interested, but when you google Steven Murphy......this is what shows up. So I figure that I should place a checklist here.

Temperature > 101° over last 48 hours   yes____________no__________                                                                                          

Chills (physical shivering at room temperature)      yes______ no _______                    

Headache                      yes _______ no _____             

Myalgias    yes ______ no   _____ 

Arthralgias                     yes _______ no ______     

Sore throat   yes _____no ______ 

Dry cough                     yes _______ no _____    

Productive cough   yes _____no ___ 

Nausea                         yes_______  no _____    

Diarrhea      yes ____ no____ 

CXR with infiltrate         yes _____  _ no   ____    

Family members with similar sickness   yes  ___ no ___    

Contact with patient with novel H1N1 (swine) influenza   _____________

Travel to Mexico 3/09 or later _____________________________ 

Other travel ____________________________

There you have it. If you have 2 or more of these symptoms, you should be seen and evaluated.

203-863-4195 or 888-584-8999

Scuttling Navi'

It looks to me that Navi will be scuttled. I am fairly certain of that. My guess is that more and more toxic assets will be dumped into Navi and that it will go bye-bye

Well, we just found out why it is a "Bad Asset" and I have just decided that someone was being untruthful....

It turns out that it was Navi......sucking up a troubled asset to protect Affy. 
Why? Navi is now getting sued for 75 million due to patent infringement. To look at the case, you can read about it at Justia

Why would you buy a lab which could be and has already been proven to be subject of a lawsuit?

Navi is a pawn and I feel bad for their employees. Man were they suckered. Listen employees of Navi, if you want to make a real company, give me a call......

I wonder how many startups are designed for failure. This is just a huge shell game with really rich people.......VCs have multiple start ups so that they can protect their other real investments....

Just like the ThunderDome.......2 men enter, 1 man leaves.....

The Sherpa Says: If Navi lives for another year it will be to protect the investment of VCs other investments.....Sorry it had to come to that, but hey, that's business.....Now the real question lingers......When Navi goes, who will own the computerized records of its research participants or its customers?

Wednesday, May 20, 2009

Thanks To Genome Web: The Challenge to Personalized Medicine

I have long thought about this and remain convinced that Personalized Medicine is the most powerful tool to improve patient outcomes. The paradigm is clear......

In an interview I gave to Berci Mesko at Scienceroll 
a while ago.....I made clear that there is a difference between personalized medicine and personalized genetics.

I know want to make another important distinction......until personal genomes can improve lives by altering current medical care or behaviors known to increase risk of disease, they remain NOT PERSONALIZED MEDICINE!!!

So they should not be lumped into the same category as Personalized Medicine.

They are what they are. Personal Genomics recreational testing.......Unless of course they are giving you data about disease, but that of course is a different animal....

I am in awe of what is going on.

This amounts to quants in a 100 story building in Manhattan arguing about Re-Insurance of assets located in Topeka Kansas.....

This is precisely what got us into the financial mess we are in....

Who knows how things work? The people who do those things on a daily basis? Who "thinks" they know how things work? The people who "created" those statistical things....

Who is right? Well in this case the pragmatic answer is this......

Find a test which replaces the current testing we do to identify risk.....prove it works and then deploy it.....

In the current GenoHype Schema, what we have is backwards..........We deploy tests which haven't been proven to work OR replace current testing for risk stratification.....And hope to hell someone proves them to be correct. But when they are disproven (is that a word?), we write letters to the editor attempting to tear apart the research...In Futility...........

I hope you get my point......DTC Genomics has created a Personalized Medicine Bubble which is set to pop because of overhyped promises......

Francis Collins' statement that "the worst thing we could do for personalized medicine is oversell its promise" is now coming true and the Quants from Biotech may fall just as hard as those from Finance.......

The Sherpa Says: Personalized Consumer Genomics is for recreation. Personalized Medicine IS for Medicine......Let's not mix the 2 please.......

Tuesday, May 19, 2009

Author smackdown....Sorry Dr Kari

I just received an email from Annals of Internal Medicine and I see a letter to the Authors from Dr Gulcher and Dr Stefansson. I chuckled to myself because I just finished writing a letter to the editor and had another published in Nature Biotechnology entitled "In Need of a Reality Check"

Why did I laugh? Letters to the author or editor are written to clarify issues or problems with articles in a NON-Peer Reviewed Manner. They are done to make points for the avid readers of the Journals.

It turns out that Doctors Jeff and Kari have found fault with an Article published by Dr. Ridker and Dr. Paynter PhD.....this article showed that the addition of 9p21.3 SNP data to the reynolds risk predictive model, which already includes family history of early heart disease and CRP markers....

This addition of a highly replicated SNP data ADDED ABSOLUTELY NOTHING to the predictive value of this current predictive model.  This is no surprise to me. You essentially covered almost all of the genetic factors that add big risks......blood pressure, cholesterol, family history, smoking why would this test add anything????

Which brings me back to the issues.
1. Dr Gulcher and Dr Stefannson work for a company selling a 9p21 medical genetics test.
2. They think that the study is skewed because the study population is 50 year old caucasian women. (BTW, this is the hardest population to predict risk for)
3. Gulcher think that a higher risk population would benefit from their test.

What is funny about letters to the author is the fact that the authors get to defend themselves and often have the last say.....So what did the authors say about these arguments which were posed by the Chief Scientific Officer and CEO of a company which is selling the 9p21 test (Sarcasm included)?

The Author, Dr. Paynter says
1. The argument that reclassification would occur more often in high risk patients has not been proven and is presumptuous.
2. The studies cited for support by Dr Gulcher and Dr Stefansson didn't examine whether the reclassification was more accurate.....i.e. if it is a misclassification, does it count as effective? Not so much.
3. The utility of the Net Reclassification Improvement is valid and that the attack offered up by the deCode team misunderstands what the NRI really is.....

All in all, Dr. Paynter laid the smack down on the Doctors from deCode.......
BTW, this study is great evidence as to why the bar is so very high for reclassifying patients with any risk for heart disease based on anything other than those which increase the risk greater than the current non-genetic risk factors....

The Sherpa Says: I remain convinced, predisease risk prediction based on SNP data is much weaker than current clinical tools.....WHICH HAVE BEEN STUDIED FOR DECADES!!!! Not less than 2 years.....Newly discovered risk markers will require 5 to 7 years to validate and another 5 to be implemented....Plain and simple.

Friday, May 15, 2009

Wolfram Alpha destroys 23andMe's Strategic Advantage?

One of the good things that I thought existed with 23andMe is that they have a nice agnostic platform which aggregates information on certain SNPs, similar but not the same as SNPedia........Let's face it, any knuckle head can do the social networking. But the hard work was the data aggregation......

Either way, what I like about SNPedia and Prometheus is it is sort of free......

You do have to dump some data into it......As opposed to paying 399 USD to have access to it and your Million SNPs.
But now I have seen the death of these sorts of company models......

Really? How?

Something called Wolfram Alpha....

You can watch the screencast into as well....Very simple, semantic web stuff.

But what is amazing is the possibility of "Wolframming" a Gene or a lab test or a SNP......

What was cool about 23andMe is that you can get the studies of each SNP.....but in this case imagine, getting the SNP, all the studies and perhaps some links to commentary regarding this.

Wolfram Alpha will be able to do this. Why? EnSembl, PubMed, et cetera.....

So what was a cool database that a company may have built will become nothing compared to what is already in the public knowledge base from the government. This is the Killer App for a whole host of businesses........Including Bloomberg Terminals.........

This system is very scary.......and very exciting all at once.....

The Sherpa Says: Personalized Medicine just got more personal with the potential of using Wolfram Alpha to run a Reynolds Risk and tell you how your diet can improve your risk.......

Thursday, May 14, 2009

The Wicked Witch? Or Not?

Ok, so everyone knows now that ACMG is suing Myriad for patents on BRCA1 and BRCA2 testing...........

Let me be the first to say that patents stifle research. At the same time patents don't stifle innovation. In fact they actually reward it. And they also give lawyers a job.....aside from Congress, these days this may actually be the only business lawyers can get steady work from......

Myriad has built quite a company out there in Utah in case you have missed it. The stock is trading at a decent 32 dollars a share, they have money in the bank and are most importantly delivering a very needed service.

In addition, they are helping patients discover risk and have some very useful sets of information and patient support. They also do philanthropy BTW.....

So I have to ask myself, should we punish someone who is doing good? The answer is a resounding yes. Laws exists and courts of law exist to hash out differences.....whether they are hairbrained or not.....

Trust me, I have seen hairbrained differences.........and accusations.......

What the ACMG is bringing is not exactly hairbrained......

That being said, if the monopoly on this test is removed, we will soon see the true and complete race to the bottom for ALL MOLECULAR TESTS......for those that think this will ONLY affect Myriad, think again.

My guess is that this move is designed to bring BRCA testing in house in a whole host of academic labs....where the send a bundle of these tests of each year. I know, I saw it first hand.......our Ashkenazi Mutations were sent off to Allen Bale's lab, NOT Myriad....

I am still trying to figure out how he saw all of those patients.....

Anyways, I digress......If the patent is removed, then this will be a deathblow to things like APOE testing and the like......Clinical DX and the 5000 USD familion panel will be destroyed AND more importantly, this may prove to be a huge disincentive to have a small boutique lab doing rare diagnosis.....i.e. GeneDx

What we would soon see is the huge shift of these labs into large academic centers and the roll up of these little labs into the big guys who can then deliver testing at a cheaper rate....not necessarily better, but cheaper.

The legal challenge here is whether gene patents are uncostitutional or not. It turns out that the USPTO is part of the lawsuit as well. Yes, correct. The very body which issues patents is being challenged......My initial gut says.....when you fight the government and the administration is pro-gov' will likely lose. But in this case, we could see the opposite.

In addition to several individual women patients and researchers, plaintiffs in the case include: the Association for Molecular Pathology; the American College of Medical Genetics; the American Society for Clinical Pathology; the College of American Pathologists; Breast Cancer Action; and the Boston Women's Health Book Collective.

I would love to hear the opinion of my legal experts here....In fact I have sent out feelers to the best IP and Personalized Medicine attorneys in the land......I will let you know what they say shortly.

In addition to the illegal nature of patents, they are also arguing that it is against the First Amendment to patent scientific knowledge...

This case is landmark and likely will go to the Supreme Court (My Guess)
The Sherpa Says: Beware the hand that feeds you.......and in this case, Myriad probably should have dropped the price just like 23and- did when the economy turned south. In a recession AND a healthcare crisis it is NOT, I repeat NOT a good idea to screw with Medicare by charging 3000 USD for a molecular test.....Or Drew covered in pink in a picture from over a month ago.....

Wednesday, May 13, 2009

RIP Richard Grasso

Richard Grasso. No not Dick Grasso. Rich Grasso, a good friend and uncle died Thursday. Since then I have been struggling to find meaning in what I do.

My Uncle, well, my uncle-in-law, was one heck of a guy who lived life to the fullest. He had so many friends. I remember meeting "The Family" when I was dating my wife and how scared I was......Richard said, don't sweat it, we don't bite......except for Nanny.

He always had a way of making me feel warm and loved. He gave the best hugs and always gave great advice. Unfortunately, he died because he forgot to do one simple thing. He forgot to wear his seat belt. He was thrown from his car and that's what killed him.

It seems to me, after this swine flu thing and now with my uncle.....all of this overbloated hype about genomes saving the a little too much.

If you look at the fatalities data in 2008 it is crystal clear that the people getting their genomes scanned should pay more attention to whether they are driving safely and buckling up rather than spitting up. Sure we are reducing the rate, but how many really have to die?

Not to say that genomes aren't worthy of study. They are. But Today I want to make sure that each and every reader of this blog, buckles up when they drive. That they forget about using the cell phone in the care. That they decide not to cut off that other driver.........or just stop rushing to beat the light.....

If we all just did that for one day, we could save more lives than any amount of genome scans could......

The Sherpa Says: God Rest Richard Grasso, please learn from his mistake. Drive safely, drive as if getting there late mattered less than getting there alive.......

Monday, May 11, 2009

Thoracic Aortic Aneurysms and Stroke

Today I am writing to bring your attention to another gene found in Thoracic Aortic Aneurysm. There is a nice genetic review on the subject at

The problem with Aneurysms is that they are essentially ticking time bombs in the body often waiting to explode and ultimately kill you by bleeding in your brain, chest or belly. Kind of makes SNP scans look silly compared to the life and death issues here. In fact, sometimes armed with merely a family history you can find these people and save their lives.

Cardiovascular manifestations of familial thoracic aortic aneurysms and aortic dissections (TAAD) include: (1) dilatation of the aorta at the level of either the ascending aorta or the sinuses of Valsalva; and (2) aneurysms and dissections of the thoracic aorta involving either the ascending or descending aorta. Cardiovascular manifestations are usually the only findings. Affectedindividuals typically have progressive enlargement of the ascending aorta leading to either aortic dissection involving the ascending aorta (type A dissection) or consequent tear or rupture. The onset and rate of progression of aortic dilatation is highly variable.

TAAD is inherited in an autosomal dominant manner with variable expression and decreased penetrance. The majority of individuals diagnosed with familial TAAD have an affected parent. The children of an affected parent are at 50% risk of inheriting the mutant allele and the disorder. Prenatal testing may be available through laboratories offering custom prenatal testing.

I take care of a few patients like this and you may miss this condition, unless you take a good family history. It is often described as "Heart was torn" "Sudden Death" "Abdominal Aneurysm" or even "Heart Attack"

This is why I am all about getting your family history, but then reviewing it with a medical professional. Most of our patients come back, time and time again bringing new medical information. This helps us best treat and prevent disease. In the case of TAAD, if your sister or brother or mother or father had the syndrome, you are at 50-50 odds of having it too.

Since often the only signs and symptoms are chest pain and sudden death.......It helps to have a surveillance plan. But how do we diagnose these patients?

TAAD is diagnosed based on the presence of dilatation and/or dissection of the thoracic aorta, absence of Marfan syndrome and other connective tissue abnormalities, and presence of a positive family history. TGFBR2 (encoding transforming growth factor beta receptor type II), TGFBR1 (encoding transforming growth factor beta receptor type I), MYH11 (encoding myosin-11), ACTA2(encoding alpha 2 actin, aortic smooth muscle), and two loci, FAA1 and TAAD1, are known to be associated with TAAD. Further locus heterogeneity is evident. Molecular genetic testing for TGFBR1, TGFBR2,MYH11, and ACTA2 is available clinically. Molecular genetic testing for the other the loci are currently performed on a research basis only.

One of my families with this condition actually also has a strong family history of stroke. Traditionally, we thought that this TAAD didn't involve other vascular issues. We were once again, proven absolutely wrong.

Dianna M Milewicz, MD, PhD recently discovered in a familial cohort, relation between ACTA2 and TAAD with stroke.

"Mutations in Smooth Muscle Alpha-Actin (ACTA2) Cause Early Onset Coronary Artery Disease, Stroke and Moyamoya Disease, Along with Thoracic Aortic Aneurysms and Dissections," is published early online in the American Journal of Human Genetics.
This just goes to show that assumptions are often false, which is why most GWAS come back false in the end. Because assumptions about not having assumptions can lead us even further astray. With ACTA2 I wonder why we didn't think this smooth muscle gene was a candidate before.

So what do we do to defuse the ticking bomb?


Echocardiography should be performed at frequent intervals to monitor the status of the ascending aorta.

  • Yearly examinations are sufficient with relatively small aortic dimensions and slow rates of aortic dilatation.

  • More frequent examinations are indicated in any of the following situations:

    • The aortic root exceeds about 4.5 centimeters in adults.

    • The rate of aortic growth exceeds about 0.5 cm per year.

    • Significant aortic regurgitation occurs.

The entire aorta should be imaged every few years, as the incidence of aneurysms in other portions of the aorta may be as high as 20%.

After repair of the ascending aorta, the remaining portion of the aorta needs to be routinely imaged for enlargement of the distal aorta, whether the individual had a type A dissection initially or underwent prophylactic repair of the ascending aorta.

Periodic imaging of the cerebral circulation in individuals with a TGFBR2 mutation to evaluate for cerebral aneurysms is recommended as these aneurysms may occur later in life.

Hemodynamic stress. Medications that reduce hemodynamic stress, such as beta adrenergic blocking agents, are routinely prescribed for individuals with the Marfan syndrome, and similar treatment is recommended for individuals with familial TAAD [Shores et al 1994]. Aortic dissection is exceedingly rare in early childhood, but aortic dilatation may be present in childhood. Medical therapy should be considered in children and adults with aortic dilatation.

Hypertension should be aggressively treated and controlled in individuals with TAAD.

Prophylactic surgical repair of the aorta to prevent subsequent dissection or rupture is indicated in any of the following situations

  • When the rate of dilation approaches 1.0 cm per year

  • When aortic regurgitation progresses

  • For individuals with familial TAAD caused by TGFBR2 mutations before the diameter of the ascending aorta reaches 5.0 cm

  • For those with bicuspid aortic valve (BAV) when the diameter of the ascending aorta is 5.0 cm

  • For all others with TAAD, when the diameter of the ascending aorta is between 5.0 cm and 5.5 cm

More recently, a valve-sparing procedure has been developed that precludes the need for chronic anticoagulation [David et al 1999].

More aggressive surgical repair may be indicated for individuals with a family history of aortic dissection without significant aortic root enlargement and in individuals with TGFBR2 mutations.

You can see that this watchful waiting and action when indicated pathway is very similar to other things we do, including BRCA positive surveillance options. This is why genomic medicine will win in the end. We will catch those who have these horrible time bombs and help prevent them. In my mind that is a home run every time. Will testing take place before a good family history? Only if we don't have the skilled manpower to take good histories and physicals.......

The Sherpa Says: I just discovered another one of these families last week. I will say it again and again. You miss 100% of putts you leave short. I.E. if you don't look, you never find.