Coriell and OSU integrate GWAS into an EMR!

Ok, so enough with the acronyms.....

I am back and will be blogging more often again. So for those who still lurked around, tell the others that the Howard Stern of Genomics is back. I took a social networking holiday for a solid 2 months, plus the addition of having my practice change quite a bit after my USA Today and follow ups in the local papers.....

Today I want to announce that Coriell Personalized Medicine Collaborative and Ohio State University will be using data from an arm of the CPMC and OSU to integrate genetic risk data into the medical record.

Correct me if I am wrong, but I don't know of anyone else doing this exact same thing.

Ideally they will also continue to roll things in like PGx data. (I know this data will be coming soon)

By integrating things like Plavix response, you can make more gametime decisions easily.

I.E. Patient presents to the ED with a heart attack. Armed with prior knowledge about plavix nonresponder, you pick Effient.

What is so awesome about this arm is that Primary Care Physicians, Cardiologists AND patients will be participating and receiving results.....

They will be studying the behavior and knowledge of participants in the study, we have seen other data on this sort of thing, I wonder if we will see the same thing here.

For risk data? Probably. For PGx Data? Probably not.

Why? A plavix response in the medical record is a game changer.

3 Reasons

1. The clinician will be hit in the face with a "Plavix doesn't work here"

2. The physician may even find they are a nonresponder

3. There has got to be some hustling attorney out there, who will be lurking once they see the CPMC/OSU release. I am certain at least the physicians will be thinking so.....

You can read the Presser Here

The Sherpa Says: Study of clinical use and behaviors will be key to know how vital this data is and thus how tightly we should regulate its use in medical records i.e. 23andMe clinical BRCA testing! P.S. Like our new crest?

Consumer Genetic Testing for heart attack risk? Worthless!

Here are the top ten reasons why in its current state, direct to consumer or otherwise, genomic testing for cardiovascular disease risk is dead in the water

1. Family History Risk paints a far better picture and IT IS FREE

2. Reynolds and Framingham risk paint a more accurate picture

3. An independent panel has reviewed 58 variants, 29 genes, and gave the thumbs down.

4. The highest increased risk from any of these tests is 30%, Fam Hx can be as high as 500%

5. Kif6 was just shot down as a useful marker.

6. Clinical Utility has not been evaluated in ANY of these tests.

7. Spit Parties don't lower cholesterol

8. The FDA is hunting down these type of crazy claims!

9 . Topol's heart attack gene didn't pan out, why would these?

10. A recent 23 gene panel failed to make the grade as well.

Let me be crystal clear.

I am glad that the number one reason for ordering a DTCG test was curiosity and not true medical concern in the "early adopters"

But I am concerned that may not be the case for the next wave. I am concerned they will take these genetic tea leaves and use them.

The problem, most of these tests are disproven or will be in the next couple of years.

Loose associations with small increased risks sounds a lot like fortune telling or phrenology. Or hell, even birth order....

Someday we will have good predictive models, 10-15 years from now. But NOT Now! Do you hear that VC country, SV, NYC, Hedgies?

10 year exit strategy. Not 2 not 8. So stop hyping this bull$h!t and go invest in Gold or Commodities or something for the love of god!

The Sherpa Says: Did you hear the one about the research geneticist? He keeps telling his wife how great their sex life WILL BE! Someday we will have this tool, let's try not to burn out and cynicize the public yet.....HT Francis Collins

99 USD, DNA day and patient letters

Yes,

What a great DNA Day!

Today started with my twitter feed notifying me that 23andMe had dropped their prices to 99 USD today. Which almost had me encouraging people to get testing, until I remembered that 23andSerge would then have your DNA..........FOREVER!

Then I opened my email and read this great note

"Dear Dr. Murphy,

Thank you so very much. I am so lucky to have found your team. Who would have thought my Plavix might not be working for me? Only when you told me about how it could not work did I realize that I might be taking something that is worthless. Thanks for testing me. Now that I am on Effient I feel much safer!

Thank you Dr. Murphy,

You saved my life!"

That's right. A genetic test, may have saved this patient from a heart attack. A genetic test I do regularly. Who has this patient's test result? Not some corporation that will use it for profit. No, just me, who will use it to act medically. While as these other services say explicitly, YOU CANNOT USE IT FOR MEDICINE!!

To be certain, you should not stop your Plavix WITHOUT talking to your doctor first!

Shame on them, their test could save a life. But not according to their TOS.

I will be speaking at the Consumer Genetic Show about precisely this problem and others. I was so surprised that they asked me to speak. Especially after the beating I gave it last year.

But on this DNA Day I am here to tell you, the public is aware now. DNA testing does hold promise, but only when in the right hands.........

The Sherpa Says: Pharmacogenomic testing IS MEDICINE. It is NOT FOR $H!T$ AND GIGGLES! Happy DNA Day!

PHG Foundation and my point.

A long time ago I had a post entitled "Beware Doctors Bearing Genetic Tests" back in April of 2007. It was an interesting post where I point out that this wonderful GI doctor who was IVY league trained completely hashed genetic testing for HNPCC.

I went on to explain the shortcomings with Internists in interpreting APC testing for familial adenomatoid polyposis coli. 1 in 3 misinterpret tests.....Wait till you see the DTC interpretation!

Everyone who gets all in a huff when I say that these DTC genetic tests should be regulated. But I am here to say there is a good reason for it, and it has nothing to do with the people getting the tests.......There is now threat of public harm.....

But first let me explain my frustration. Saturday I was on Twitter and Daniel MacArthur and I had a conversation, which he lead off by saying:

"@helixhealthct Just shows how arbitrary most medical care is anyway; not like it'll change the outcomes much.2:46 AM Aug 22nd from TweetDeck in reply to helixhealthct"

Which was in response to a PHG report on an article published in Genetic In Medicine [Kolor K et al. (2009) Genet Med 11(8):595].

Among the 1880 physicians sampled, 42% were aware of the tests(DTC Genetic tests) and, over the past year, 15% had at least one patient bring the results of such a test to them for discussion. Interestingly, of this latter group, 75% (212 physicians) indicated that the results had changed some aspect of their patient’s care.

Holy Crap! Really? 75% changed the care?

So it had me begging several questions.

1. Did the physician read the Terms of Service for the DTC test? "Not to be used to make medical decisions"

2. Did the patient read the Terms of Service when they brought this test to the physician.

3. How is the physician supposed to know that this is not a clinically validated genetic test?

4. How is the busy clinician to differentiate this test from other clinically valid tests?

5. Why did the patient bring the test to the doctor? Was it due to DTC marketing efforts?

I was pissed at Daniel. How dare he say what we as physicians do changes no health outcomes!

In some instances he may be right. In others I wondered how complaints may actually be neglected based on this "genetic test"

Did these 212 doctors know something I don't about the utility of this DTC testing?

I doubt it.

I am seriously concerned that the 3/4ths of the 18% had actually changed care based on a non-clinical based test. That, to me is Scary AS HELL!!!!!

Think on this for a second.....How many of these doctors will ignore chest pain complaints based on a low genetic risk?

Now think on this. How many doctors will unnecessarily order stress tests for patients who have no complaints and are "High Risk"?????

Either way you slice it, 3/4 of these doctors are acting incorrectly, or at least not according to evidence base.

This survey proved one thing to me. Doctors have no F^CK!n& Clue what they are doing with genomics!

Why should these tests be regulated?

1. Patients aren't following the terms of service, likely due to deceptive advertising

2. Doctors can pose a threat based on inaccurately using these tests

3. Over use of resources could end up being a big problem because of these tests.

4. The potential for public harm has now gone from silly consumer, to trained medical professional inflicting damage.......

The Sherpa Says: Like I said, beware doctors bearing genetic tests........and patients too.

Family History, State of the Science

The NIH/CDC is hosting a conference next week. I conference I wish I could go to, but alas, I will be DOING family histories on my patients that week.

The conference will be held at the NIH in Bethesda. This is an NIH state of the science conference about Family History and its usefulness.

I for one, am very glad that the government is trying to address this super important issue. It is beyond due for an evaluation.

Why?

With the cost of a genome going to drop to 5000 USD by the late fall (trust me), we will soon see another level of DTC and Clinical lab set offering the genome as a predictive tool.

There are several reasons that Family History beats a Genome (For Now)
1. Phenotypic data of family history represents complex interplay of genes and environment

There is no way that a simple genome will be able to give us the story of how a human will develop. That is predicted by environment and genes, which are successfully covered by..... A family history.

2. 5000 USD is still more than what it costs to obtain a family history.

By the time the software tools are released, we will see that social networking and the internet will transform the costs of family history next to nothing. Which is still a long way to go for the genome scans.

3. We have no clue what most of the genome data means.

Indels or CNVs or SNPs, we have no freaking clue what most mean, we do know what a heart attack at 40 means.......

4. Even if we had everyone's genome scans, we would still need phenotypic data and pedigrees.

What's the one thing we do when we have an intellectually delayed child with an abnormal CMA/CGH? We test the parents. Looking for THEIR phenotypes to make sense of the genome mess.

Look, people always give me reasons why the genome is important and a family history is useless.
I've heard them.

-"We don't speak with that side of the family"
-"My father lived with his uncle, because his father died (secretly running the empire as Darth Vader)"
-"I was adopted by Bail Organa, only to find out I have a lost twin brother"

There is one thing that will always be certain over time, there will be some screwed up family dynamics making it difficult (BUT NOT IMPOSSIBLE) to obtain an accurate family history.

That being said, it is still often useful to capture those who you can. And still less expensive.

I look forward to the briefings from this conference, and Muin, if you are listening, I would love to have the link to the webcasts.... Oh wait, they have that too! Sweet.

If you can't be there, you can get the information you seek!

Once again, we need a state of the science on genome prediction, not a consensus statement a real eval of the state of the science. When placed side by side with the state of the science for a family history, we will soon see why family history is the preferred screening tool and will likely to continue that way, perhaps in conjunction with a genome scan, but genomes will NEVER replace family history.

The Sherpa Says: The press better be at this conference and report on Family History. And to the founders of Geni.com, you missed on this one when Tindall presented to you. Or maybe you just are going to steal the idea.........

Duh!!! For at least 5 years we "knew" this!! PPIs and 2C19

In case you missed my further rants about how everyone on Plavix should be tested for 2C19 polymorphisms, often splice site changes, which could hinder the effect of plavix......Now a big fat , No Duh....comes out in the Journal of the American Medical Association.

Let me lay the ground work.........

Plavix, one of the top 3 medications in the world

1. Prescribed to prevent a second heart attack or stroke


2. Prescribed to prevent a clot forming in a coronary artery stent, which one often receives after having a heart attack


3. Given in patients with PAD

It turns out that in order for this medication to work it needs to be converted from Plavix into its active metabolite. This type of medication is called a Pro-Drug. There are others like this, including tamoxifen and codeine.

Well, the enzyme which converts Plavix to its active metabolite is called CYP 2C19. We have known this since 2000. A professor of mine actually published on this back then. We even knew about so called "Plavix resistance" .

We know theorize that Plavix resistance is mainly due to polymorphisms in CYP 2C19. This has been studied since 2000, but only recently came to major light with articles in Lancet, New England Journal of Medicine......and my rants on this Blog and in Lectures at Yale and Affiliated Hospitals....

Now........the fly in the ointment....

Proton Pump Inhibitors(PPIs) like Prilosec and Protonix........Are available over the counter since they are so "benign"......

Well, we have known and studied since 1997 that Prilosec inhibited 2C19's ability to biotransform other medications.

So what about allof the people taking BOTH Plavix and PPIs? Let me guess.... the results are like the data in 1997!!!!! That patients receiving both medications have little Plavix effect and decreased platelet inhibition.

Well, that was shown in 2006 and even some preliminary data in 2004.

So one has to ask, well why haven't we put anything on the label? Why haven't their been huge warnings....even more so....how many people are on Plavix and PPIs? The pharma companies know.......how come they haven't warned people pre-emptively that there "May be a problem"

The FDA always asks how much evidence is enough.....but now with the study just published in JAMA it is painfully clear.....we have missed the boat by requiring TOO MUCH PROOF!!

What does the study say? Those who are on Plavix and Prilosec are 27% more likely to have a recurrent hospitalization or DEATH from acute coronary syndromes than those NOT ON THIS COMBINATION!!!

AND, 2 of 3 people in this study on Plavix......were ALSO on Prilosec!!!!

This study was a retrospective study which does have limitations, but has me asking why do we have 3 years of data on this combo 2003-2006, when we knew that there may have been a problem back in 2000????

Why didn't we do a better post market analysis?

What's even worse......people advocating pharmacogenomics are getting push back from lazy clinicians who are asking for randomized double blinded studies to PROVE this problem.....

But here's what they don't know.....the pharmacology literature is robust with Pgx data, just as it was with PPI 2C19 inhibition data....Too bad doctors don't read pharmacology literature....

Anecdotally, when I was a resident, I pulled all of my patients off PPIs that were on Plavix. What did I do? I did a med reconciliation and became aware of the possible interaction.....In this case it was NO BIG DEAL to put them on H2 blockers instead......

Primum Non Nocere.......not PRIMUM RANDOM DOUBLE BLINDUM.....

This just pisses me off.........9 years to come to clinical light........That is a damn shame, That may also happen with Prasugrel....

The Sherpa Says: Why do we as physicians wait for a large organization to say stop, when we have the education to figure out from the literature when we should have stopped? Or for that matter, when we should have started......the burden of evidence has been overcome here.....Unlike SNP Scans.......

Copy Number Variation, Epigenetics. Bio 400? No, NatGeo!

I was watching National Geograpghic HD last night. Yes, I do have a few minutes to watch TV. I always love to watch their in the womb specials. This time it was Twins.

What I love is the way they tell the story and teach the science (very lightly). I have to say, I have tried to teach doctors these subjects for a while now and most of what I get are these blank stares.

NatGeo has these wonderful graphic animations and weave a story around the animations with real clinical examples that bring the science to life.

Maybe we need to start having physicians watch NatGeo. We could scrub NCHPEG and anything EMedicine or UpToDate has to offer (which are average tools and topics).

Why? In one brief 60 minutes episode of NatGeo, they covered

1. Twins have epigenetic differences, explained epigenetics including methylation and presented Russell Silver syndrome in an Identical Twin

2. Identical Twins have different Copy Number Variation, yes they even explain what CNV is! BTW I mentioned this in the Autism studies being done up at Yale

3. They presented a MZ twin set where one boy was gay the other straight, v. interesting stuff on testosterone sensitivity.

They then took the fact that these people were identical and showed how based on these other subtle genetic differences they were at different risks for diseases.

This is probably one of the best ways to teach physicians, via case based learning and science. The big problem? Those episodes cost perhaps a million dollars to make. I don't see anyone handing over that kind of money in this economic environment. But what if they did? What if there was a channel just for physician education that produced such films? Sure the public could subscribe too.....what a great freakin' channel!

Yes, if we could have TV teach the physician we may be better off. Just an hour a night. 3 nights a week. Imagine how quick we could jumpstart the Personalized Medicine revolution. Turn off Grays Anatomy and tune into something worthwhile. But alas, most doctors are looking to escape medicine when they turn on the TV, not learn. But if you offered CMEs???? Might be something there....

The Sherpa Says: Why does it take a million dollar budget and a set of production professionals to create a palatable lecture on epigenetics? Alas, because the scientists and physicians have the Curse of Knowledge.

Not Again OMG UK!

In another amazing step towards eugenics. Britain has awarded a couple the right to prenatal test for familial hypercholesterolemia. This way they can then terminate a pregnancy that may results in a child plagued with the disease of high cholesterol and heart attacks. In the Times

FH occurs in two forms. The more common version, heterozygous FH, affects 1 in 500 people. It is caused by a single mutated gene, which raises cholesterol and thus the risk of hardened arteries, heart disease and stroke. It can usually be managed with statin drugs and diet.

Britain’s first licence to test embryos for FH will be awarded next week to Paul Serhal, of University College Hospital in London, by the Human Fertilisation and Embryology Authority (HFEA).
Its decision breaks new ground because it permits Mr Serhal to screen out not only the severe form of the condition but also the milder type, which is usually treatable.

In addition this brings the thought of pre-implantation genetic diagnosis (PGD) for the disease. I know many people who are heterozygous for this disease. I treat them with cholesterol medications. Do I tell them they could have PGD? No. Do I tell them that their children will be at risk for heart disease? Absolutely. Is this a treatable condition? You bet. Can it be devastating? Yes. Does that mean we should PGD every gene you may not want? Hmmm this sounds familiar.

So where do we go from here? Gattaca.

Well, this certainly is a slippery slope. Let me know your opinion. This Times readers opinion says is very nicely

Lucky for us that the parents of (Agatha Christie - Alfred Lord Tennyson - Algernon Charles Swinbunre - Blaise Pascal- Charles Dickens Dante - Edgar Allen Poe - Edward Lear - Fyodor Dostoyevsky - Gustave Flaubert - Guy de Maupassant Lewis Carrol - Lord Byron - Professor Manning Clarke - Pythagoras (Philosopher & Mathematician) Sir Walter Scott - Socrates - Truman Capote) weren't tested for Epilepsy. Our world would be a much less interesting place.
Martha Ware, Hammonton,NJ, NJ/USA

-Steve

Scienceroll reviews Personalized Medicine Companies

Today, Bertalan Mesko at Scienceroll has reviewed three companies. Navigenics, 23 and Me, and Helix Health of Connecticut of CT. For full disclosure, I am not only the owner of Helix Health of Connecticut, I am also a patient. My family has a significant genetic background for disease. Because of this, I was motivated to change the paradigm of current medical/genetics practice.

Berci does a nice job of describing the companies and what he estimates their best attributes.

"If we could merge the real advantages of these companies:

• the fantastic team of Navigenics and their unique business model;
  


• the financial background of 23andMe; the focus on genealogy information and social networking;


• the personal aspect of Helix Health of Connecticut and their potential to serve and help physicians as well,

…then it would be the perfect service. But it’s impossible to compare them properly as they are all unique in their own way and will probably find their base of customers."

I have to say that I am in agreement with Berci, I wouldn't mind working with Navigenics or 23 and Me to help shape this field known as personalized medicine. I have had experience with the multiple legal issues involved in providing telemedicine and other scalable services this way. But I must re-emphasize that nothing gets truly communicated unless the patient has the ability to ask questions, over and over again. Can someone who has never been trained in medicine answer medical questions? Yes. Will they be protected from litigation? No. Will they provide insightful answers....I leave that answer up to you.

I don't believe it is a smart idea to cut out the health care provider from this equation. Full Disclosure (I am a health care provider). But that's not why. I have seen it done the other way. I have seen patients who have had DTC testing. They have received services from certain unnamed companies and couldn't understand what was going on. Even worse the needed some re-assurance but the phone counselor obviously couldn't see the patients face. So all in all they came to me for personalization. The true key to personalized medicine.

The Sherpa Says: Stay Tuned to Scienceroll. I know I visit his blog everyday. The talented Dr Mesko has the most cutting edge information on this fast moving topic. He is my own personal Sherpa. By the way, make sure you vote, there are 4 days left. It's all tied up. "How much is a Sherpa worth to you?" Some of my readers feel like they could take a course to be a sherpa, Others already are Sherpa's, some are looking for a sherpa, and the last want to climb Mt Everest with 1 cleat, a windbreaker, and Wikipedia as their guide. Which are you?

What the F*&^

After reading Hsien's recent post, I am convinced how very much the UK needs a Sherpa. Listen to what is going on in Great Britain from Eye On DNA.

"The UK Human Fertilisation and Embryology Authority has approved the use of preimplantation genetic diagnosis (PGD) to select embryos free of the gene for early-onset Alzheimer’s disease (AD). The couple who applied has a family history of the disease on the man’s side. His mother, grandmother, and two uncles all died from early-onset Alzheimer’s."

Human Genetics Alert has been fighting the good Sherpa fight for years. The problem....the UK is still approving these techniques. I hate to tell all of you, but this is what is coming. Why scan a genome? Why do lightspeed sequencing when you have time to wait? Why? The answer is simple. To rapidly screen blastocysts to rule in or rule out suitability for implantation. I have spoken about Reproductive, Endocrine and Infertility Specialists penchant for not caring about epigenetic implications

Future Pundit talks about the role of Preimplantation Genetic Diagnosis and its ever expanding uses. The specter of looks and intelligence for PGD rears its ugly head. Do I think this is a slippery slope, you bet. Especially when at the REI conference this April there were comments such as "We are the new geneticists" and "We determine mankind's fate" were heard by my Specialist friend. Yikes here comes Aldous........

Let's face it they have yet to standardize the medium in which embryos grow. Has anyone done a solid analysis of the alteration methylation patterns that emerge while growing embryos in different media? Wouldn't it be crazy if these PGD children had some increased risk for cancer? It could happen. This is why you can't perform PGD for mildly increased risk. Why do we call a woman greater than 35 Advanced Maternal Age(AMA)? Simple, because that was the age at which the risk of miscarriage from Amnio equalled the risk of having a child with chromosomal anomaly. Now that the risk is decreased to 1 in 400 will this change AMA? So here's the question now.

Is the risk of having an epigenetic change in your genome predisposing you for cancer etc EQUAL to the risk of disease from polymoprhism in the embryo?

The Sherpa Says: Risk = Benefit is what physicians should always think about. Just because we don't know the risk DOES NOT MEAN THERE IS NO RISK!

Genetic Disease? Isn't she too Old for that?

You know, it never seems to amaze me. I received a phone call from my friend at a very solid academic training program in internal medicine. He said that he saw a patient the other day who had an unusually low Good and Bad Cholesterol, a high triglyceride level and a big liver.

While he was in morning report (This is where doctors present the patients they admit from the night before) he presented this young lady. She was a 30 something year old woman who had a cholesterol level that was off the wall. Normally a premenopausal woman would have an HDL of 50 or 60, maybe even 70. Her LDL (bad cholesterol) would be perhaps 100. If she had familial hypercholesterol levels perhaps even as high as 200. But what he found was just the opposite.

Her good cholesterol was less than 10, her bad cholesterol was 12. Why ever would she have such low cholesterol? Now this is where it gets interesting. He told the "Professors" that he was concerned his patient may have a condition called Tangier's disease, a genetic disease. What ensued was scary. All of these skilled physicians said: "A genetic disease? Isn't she much too old for that?"

Ladies and Gentlemen, this is the current state of medicine. Tangier's disease presents in the 30s and 40s with renal failure, heart attack, stroke. Why? Because it is never detected until it is too late. Even more scary is the fact that a 30 year old woman would not have an internist nor would she have ever had her cholesterol checked!!! But if you read a prior post of mine, it really should be no surprise at all.

The Sherpa Says: It is a new century, we will soon have genome sequencing for less than 1000 USD, and we are not teaching our residents properly. Why? Because the teachers were never taught. In a world where there are less than 100 geneticists trained in adult medicine how will we ever teach our future doctors? What good is you genome if your doctors think it only applies to children? Lastly, There are 7 days left to vote. How much will you pay for your genome.

I want my Genome!! What about your cholesterol?

Today I read something that blew me away! While Myriad is hammering away on NYC TV to get your BRCA test. 10-15% of all breast cancer patients have BRCA mutations in either 1 or 2. These tests cost over 3000 USD a piece, even worse, there are very few clinical changes that result from positivity of either mutation.

The stat that hit me like a punch in the nose was "80 per cent of women in the US between 18 and 44 don't know their cholesterol level" I couldn't believe it! This according to a recent survey by the Society for Women's Health Research (SWHR). This non-profit agency "encourages the study of sex differences between women and men that affect the prevention, diagnosis and treatment of disease".

This is what I find funny. A patented gene test can have a multi-million dollar ad campaign, but women's heart health gets barely a whisper. Despite heart disease being a much bigger killer in women. If you thought carrier status for breast cancer was a big deal. Having an elevated cholesterol is the closest thing to having a heart attack. Even worse, there are some simple preventative things you can do for cholesterol and it doesn't include surgery or medications.

So while we all bask in the glory of The Personal Genome Project and 23andMe, we need to get a grip. Just because you can get your genome sequenced, doesn't mean it will tell you your cholesterol level. Clinical acumen is what is required for personalized medicine, not technology alone.

The Sherpa says: According to this study "More than half of the women 18-44 surveyed were concerned about cholesterol, but the vast majority weren’t aware of their personal cholesterol level and one-quarter did not even know how cholesterol is tested" Why? Because we don't have Quest lab reps stopping by your PMDs office telling you that you MUST test women's cholesterol. That means asking your physician to check your cholesterol is up to you!

Readers' Corner

I just wanted to highlight a comment made by one of my readers. I think it illustrates the point of screw your safety, we're taking this Prime Time

From my comment section:


I don't disagree that there is and will be a "gap phase" but the assertion that "overselling genomics could ruin the promise of personalized medicine" is ludicrous! The technology is going wherever it can no matter what - the more "wild west" the approach, the more tracks get followed, then darwinism (and capitalism) takes over and the worst ideas die off anyway. Otherwise, why don't we still have people with red flags walking in front of our cars? Where is the grand thinking that took the US to the moon nearly 40 years ago? "Nanny-state" thinking and unnecessary caution is this country's worst enemy.

Nanny State?

I guess child labor laws are nanny state.

What about making sure children's toys don't have lead paint on them? Oh, but that would be nanny state too. Clearly interfering with the progress of corporate america...




The Sherpa Says: I hope this comment puts this square in your face. Let the buyer beware, because the seller isn't going to. I imagine they did a boatload of calculations and assurances of safety PRIOR to ever launching that rocket. You always should when human safety is on the line. But heck, why should we with genomics in medicine? That would just be a nanny state. The lack of regard for human safety and medical malpractice is disgusting........ To this esteemed reader. I agree to disagree.

Send in the Clowns......

The Gene Genie is at Microbiology Bytes this week. The theme is bugs and beyond. It has been 7 genies since my hosting and the topics just keep getting better. I am so impressed by the set of links posted, from evolutionary bacteriology to pharmacogenomics there is a lot in the bottle this go 'round.

I have been moving off topic lately and I promise to start redirecting. I have been guiding your attention towards the business side simply because there are so many shenanigans out there. I firmly believe that the revolution known as personalized medicine will be manipulated, just as the "organic food" wave was. Pretty soon you have everything from organic food to organic car washes.

Perhaps the next move is Procter and Gamble releasing Genomically Targeted Food, personalized just for you. Where will this start? Not in your foods, but in Fido's. I have recently discovered from several sources, including I guy (venutre capitalist) who I bumped into waiting to buy power ball tickets, that there are several food manufacturers working on nutrigenomic cat, dog, and parakeet food!!!

All that glitters isn't gold and all that buy it aren't fools. They can be tremendously smart people that are duped by marketing. I ask that we all take a step back, take inventory and prepare for the avalanche of marketing about to hit the air waves.....From Myriad and Sheryl Crow to Puppy Chow...please don't dismiss Personalized Medicine as more of the same charlatanism. We have something revolutionary, it is a shame if we let the PR, Marketing, and VC fools run us into the ground for a cheap buck or two!

The Sherpa Says: Thanks for reading.....please stick to the trail and we will get there safe and sound, I promise. Oh and BTW, I am still awaiting Salugen's studies and data.

What good is a map?

Imagine being stranded on a raft......An object is floating in the water. You paddle hard to get it. Once you do, you realize its a map. Hooray, you can finally find some land. Or can you?

There are some significant questions to ask yourself prior to having any utility gained from that map.

1. Can you read the map? I used to be in the Navy. We learned how to read nautical maps. But my father, a retired colonel in the Army, would have no clue where to begin. Imagine someone who had no training......


2. Where are you on that map? If you have no orientation, how could you hope to navigate. Where does the sun rise? Simple question. However, when asked almost 15% of Americans do not know the answer.


3. What is on the land you will be paddling to? If you paddle hard to get there only to find out that there are man eating natives, how good was your choice? Did you really want to find that land?

A map of your personal genome is much the same. Jason Bobe over at the Personal Genome comments on some of these topics. Who should be able to read the map? Should everyone have a Tom-Tom or Garmin? Should there be age limits on querying ability. And what if we find out something we didn't want to know? These are serious questions.

The Sherpa Says:

There will soon be a personal genome option. Everyone will be able to have an economically priced copy. We need some guidance on its interpretation. Personally, computers can only do so much. With all apologies to my colleauge Tim Arimond, we cannot program our way out of needing human interpretation. A computer cannot tell when you are scared, confused, upset......yet. I think that personal genome sequencing holds tremendous promise.........But it is only a map.

WikiPedia Meets Genetics

I just received an email from one of my readers today. Trip said " am med student at Univ of KY, interested in medical genetics and have been reading your blog.........I am recommending http://www.snpedia.com/ for a blog post on the gene sherpa" Well Trip....You Asked for it, You got it..... As they say on that old Toyota commercial....

First I would like to mention that my friend Bertalan over at ScienceRoll commented on this Yesterday. He did an excellent job. Also SNPedia has their own blog although there are only 2 posts so far.....

So Single Nucleotide Polymorphisms (SNPs) are little genetic changes, much like letters in a word. There is some data out there which shows taht when readign a senetnce letters in the middle of a word do not alter the readers undertsanding. This could be the case for a SNP, it may result in no change in the protein function. Or it could be the case that a SNP may change the word altogether.

Even crazier is when a SNP isn't even in the coding region of a protein. This may affect a protein as well. When we make mRNA there is a process called splicing. This splicing could be altered by a SNP located in an intron (noncoding region of a gene) or it could be located in an another gene and affect the protein by epistasis........

Listen, this is all confusing. Much like SNPs are...... It reminds me of other "genetic markers" like HLA haplotypes. No one knows what role HLA B27 has in ankylosing spondylitis....it is just linked to an increased likelihood of having the disease.

So what about SNPedia. This is a catchy idea. There exist several databases out there including OMIM. However, the more databases, the better. If we can cross reference these for validity it certainly would be nice.

In reviewing SNPedia I performed searches on several SNPs including in TCF7L2 and CCR5. The database has listed some but not all of the associations within each of these "genes" in fact CCR5 is not only an HIV associated gene, it is also implicated in abdominal aneurysms.

The Sherpa Says:

Any database is only as good as the data in the base. I feel that opening it up to public contribution through wiki is a great idea. However, we must assure the public that SNPedia will be monitored by a knowledgeable set of curators.

Britain Needs A Sherpa!

I just received an email from a reader who pointed my attention towards a popular morning program in the UK. They interviewed a person who had taken a genetic risk test despite the significant cost (I am uncertain of the test). The costs online are up to 1000 pounds, almost 2000 USD!

She did this simply because she was concerned about pancreatic cancer (her father had died of it as age 69). She announced that she was free of the risk of pancreatic cancer but had learned that she shouldn't take HRT and had stopped it.

She had also learned that she was at risk for age-related Alzhemers' (although the discussion wasn't at all clear". The discussion ended with the enthusiasm for the testing from doctor who is associated with the TV show and a call from the lay-woman that such comprehensive screening should be made available on the NHS.

My reader did think that it was interesting that there was no discussion as to the considerable potential costs to the NHS of follow-ups that have to be ordered after such screening.

The company feature in this show was GeneticHealth and from the looks of it they are cashing in on the snake oil gravy train. Francis Collins has warned of this type of testing. You can tell what they aim to do by looking at their news headlines "Could your DNA hold the key to a wrinkle-free face and a great figure?"

Thanks To Shinga Xavier for the heads up on this madness.

The Sherpa Says: How come no one in the UK is railing against a company like this. In the US there are significant consumer protection laws. Still even here they fall short in protecting completely. This woman thinks she is risk free of pancreatic cancer........Doubtful. What kind of doctor do you have on the Boob-Tube speaking the benefits of this bogus testing? The answer....He's a boob on the tube! Direct To Consumer Testing for non binary tests is absolutely dangerous and must be stopped!!! The Sherpa is Hoppin Mad!!!

The Confusing Thing About Association Studies.

Today is a moderately slow day for genetics in medicine (I can't believe I just said that). But if you want, you can sell your genome to some stranger for 5 grand USD (I can only imagine the identity theft issues) you do it at your own risk. Listen, if you are hard up for cash please do not sell your DNA sample!! Who knows what they will use it for..........Perhaps to frame you for a crime.

But what I want to really talk about is how confusing association studies can be. So lets examine some of these.

1. Long Term Aspirin use prevents cancer incidence in colon 32%, prostate 19%, and breast cancer 17%* (statistically non-significant). There is some molecular evidence of this in colon cancer. But not the others....... The catch is that you have to use aspirin adult dose for >5 years. Why? Like most association studies.....No one knows. What good is that?


2. Hormone replacement therapy increases Ovarian cancer incidence This study called the Million Women Study is a large cohort of British women. 948,576 postmenopausal women were assessed for ovarian cancer incidence. Users were 20% more likely to develop Ovarian Cancer. 1 in 5, that seems small, but in a million women (well......just 52k shy) that's alot of cancer!!! Especially such a nasty killer. But here's the kicker....


3. Oral Contraceptive hormones Reduce Colorectal Cancer risk! Wait a second.....Aren't these female hormones too? This study shows an almost 40% reduced incidence of colon cancer in these women from the Women's Health Study. Perhaps this has to do with dosage? But Who Knows....It's an association study!!!


4. Smoking Cuts Risk of Parkinson's Disease So that is what the media says about this study. Ok so now you have got me flipping out. No mechanism, No pathogenesis, No explanation.... Smoking kills, but at least it reduces your likelihood of ALSO having Parkinson's. Almost a 40% reduction in the likelihood of having Parkinson's. How? Who Cares....It's an association study! This kills me. The people could have predisposition genes for nicotine addiction/taste/etc which also have some salutatory effects. I do not think that smoking is what saves these patients brain cells!!!! But that's not what the press will tell you.

The Sherpa Says: What is sold as a good piece of science is quite often a piece of something else! Just because it was toiled over and hard work to develop it was done does not make it true, correct or even appropriate. I am here to say.....If it sounds fishy it probably smells fishy too. Throw out association studies until you have a reason for the association!!!

2 months 3000 visitors!!!!!!

Thank you to everyone who picked up my slack on Sunday. I was unable to post the Medicine 2.0 Carnival because of an illness in the family :(

I would like to tell you how excited I am that I have reached 3000 sets of eyes. I am so invigorated by this whole process of blogging. I love educating the public and physicians and this blog is a labor of love. so thank you to all the readers out there.

Lastly I would like to draw attention to an amazing film director and radio talk show host Kathleen Slattery-Moschkau . She has just produced a new documentary to the medical community called PERx…it is available for viewing via the site www.perxinfo.org The film features internationally renowned experts from Harvard and other orgs. In a short time, continuing education credits will also be available to viewers and the film is also available to the general public. All for free (in order to watch the film, click on “educational modules”)

It is an amazing documentary. She has done others including Side Effects the movie with Grey's Anatomy start Katherine Heigl

Please take the time to watch this documentary as well as Side effects. You will be amazed at what you see.

Take Care
-The Sherpa

Forbes and Genetics Part 4

Ok,
Sorry I took off Sunday. I just want to take the time to make a public service announcement. Please talk with you loved ones about your wishes if you were to have a terminal illness. Sometimes these wishes can not be conveyed and this will lead to horrible outcomes. So please, please have a living will.

Thanks.

Now back to the slugfest!
I have received even more emails about these postings. Luckily none from Lawyers yet ;)

Round 4 BRCA1 and BRCA2:
From the article-One in 500 women have mutations in one of these genes, which normally keep tumors from growing. That gives them a 50% to 80% lifetime risk of breast cancer and a higher risk of ovarian cancer, too. The test costs $385 for women of Jewish ancestry who know they are at risk for a particular mutation. A broader test looking for any defect costs $3,120.
Succinct, accurate, and applicable. However, they did not get into BART testing as I had posted about in my Blame Portugal segment. The also did not point out that BRCA testing can detect pancreatic and prostate cancer risk as well. This could have been much more informative and useful............Sherpa 3 Forbes 2

Round 5 OncotypeDX:
From the article-This test looks at 21 different genes that can be out of whack in a breast cancer tumor and predicts how likely cancer is to come back after surgery. That helps women decide whether or not to get chemotherapy, which can cause side effects such as nausea, hair loss and numbness. The test costs $3,500 and is covered by MediCare, UnitedHealthcare and Aetna.
I am not so sure "out of whack" is the best way to describe this testing. Perhaps, "whose expression leads to poor outcomes and recurrence" is a better way to describe it. Well, I am one to mince words myself so I can't get too picky. But the answer is...Absolutely an important test. This has been proven, validated and replicated.
No doubt this round goes.....Sherpa 3 Forbes 3!

Round 6 TCF7L2 testing.
From the article-This variant, in a region called TCF7L2, doubles the risk of adult diabetes if you have two bad copies of it--10% of people do. It is the strongest diabetes-promoting gene yet discovered. DeCode Genetics sells a test for $500 via online test provider DNA Direct.
Ok, before I go slicing into this test several caveats. 1 I absolutely abhor testing for the sake of testing. Especially when the result is not definitive. It leads to confusion, poor compliance and a false sense of security. I am disgusted by this type of testing. Especially when just one sibling with diabetes gives you greater information.

Now to the dissection of this claim. First, this polymorphism is a good and replicated polymorphism. But not everyone with diabetes has this change. The gene is about risk and there is no study available which show there are significant steps you can do to mitigate this specific gene risk. True you can diet and exercise just like you would to prevent diabetes anyways. In addition, the increased risk given by just this one polymorphism is not that significant. What is more likely to change your life is a panel such including genes identified by Dr Collins et. al. This study was published before the Forbes article and they easily could have mentioned all of these genes in one part. But they did not. Why? I think it has to do with the ties to deCODE. But that's just the conspiracy theorist in me.

I have an issue with this quote-"It is the strongest diabetes-promoting gene yet discovered."
Wow!! In what population? There are other genes in populations not northern European that have higher risk. This statement is almost false!!! Frankly I think we should take a point away from Forbes for this. But I won't.

Sherpa 4 .... Forbes 3

The Sherpa Says: I love how the media mixes true things into their agenda. It is a sneaky way to appear factual and credible. If they would have to submit these things to peer review before publishing, then we would have a different story. How come no one holds journalists to scientist standards? Especially when writing about Science!!