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.

Timely Release and A Unanimous Vote

First and foremost, everyone is jumping for joy since the Genetics Information and NonDiscrimination Act passed unanimously today. But, I will not rest until President Bush takes that lovely little pen and signs this into law. I hate to be called a cynic. I am a realist....But President Bush Will sign this into law. Until that, it is just a passed bill. But it is a start.

Second, the American College of Medical Geneticists has put out a statement regarding genetic tetsing and patient care. Hsien, points this out over at Eye on DNA. She does a great job of highlighting the issues. Which, once again brings me to the point that diagnosing pre-disease is just as much medicine as diagnosing full on disease.

The notable item...

minimum requirements for any genetic testing protocol.”
1. A knowledgeable health professional should be involved in the process of ordering and interpreting a genetic test.
2. The consumer should be fully informed regarding what the test can and cannot say about his or her health.
3. The scientific evidence on which a test is based should be clearly stated.
4. The clinical testing laboratory must be accredited by CLIA, the State and/or other applicable accrediting agencies.
5. Privacy concerns must be addressed.

Lastly...with the recent notes that geneticists reach will now be increasing.....We have to start having some minimum requirements.

The Sherpa Says: Well. You have got to ask yourself. If the professionals are stating these are MINIMUM requirements.....what is everyone else doing? And why aren't they all doing the minimum?

The 10k USD Gene Sherpa

It's official. Our little poll is closed. 18 days, 14 votes. That's pretty sad. But from the limited and not statistically significant data, I am able to draw a false conclusion that the public feels that a Sherpa is worth 10k/yr.

How's that for profit margin? Perhaps the readers who felt empowered to vote are geneticists and counselors, therefore obviously biasing the data. But what really is a Sherpa worth? Our Sherpas at Helix Health of Connecticut are worth that much, but cost much less.

I was asked today by an investor "Where do you see personalized medicine headed in the next five years" I answered "It depends" Over the weekend I will list my scenarios and go over what I think the outcomes might be in different scenarios, so stay tuned. One of those big scenarios depends on how the data comes out.

A few colleagues over at Coriell are looking to create some of that data. In a collaborative effort called the Delaware Valley Personalized Medicine Project they hope to give us a glimpse into how this revolution may evolve. Thanks to my wonderful OraGene rep Melanie for this info. This is precisely the type of studies that need to be done to guide personalized medicine. Marker studies are cute. Outcomes studies have teeth!

Lastly, do you remember when I said that we still have alot of convincing to do? This post at Medical News Today is concerning. Funny, in Australia they refuse cancer risk assessments, but remarkably the DTC company testing for athletic ability is doing just fine. It truly is funny where people place their priorities.

The Sherpa Says: As I talk with more and more investors it is getting clearer, maybe the money is not in Personalized Medicine. That's why Australian healthclubs are pimping ACTN3 testing.

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?

Take an Antibiotic, Lose your hearing

Before I jump into the headlines I want to make mention of a few things. First, you know that there is something to these warnings I give about DTC testing when "in the Oct. 19 issue of Science, Bolnick and 13 researchers from universities across the nation call upon the scientific community to better educate the public about the limitations of the tests, and urge consumers to approach the tests with caution."

But here's the kicker. This Article.....It has nothing to do with disease testing. The buyer beware editorial is entitled "The Science and Business of Genetic Ancestry Testing"

Did you know that close to half a million people have taken ancestry testing. With 23 and Me lauching soon, I am certain that number will double in a year.

The problems with these tests are the same that come about with disease testing. Including false positives and negatives as well as limited database information to compare your alleles to.
Sounds like the VUS problem all over again.

So why lead with the pharmacogenomic title and only mention it now? Because I am not certain this test is ready for prime time. Although, there are thousands of babies getting aminoglycosides for a condition called rule out sepsis. This occurs when your baby develops a fever during the first 2 months of life. What can happen when the baby gets gentamicin? Well, in children with this change it can cause deafness. The authors in this article "Ototoxicity caused by aminoglycosides" The authors argue the merits of pharmacogenomic testing.

The most common predisposing mutation is now known as m.1555A>G, a mitochondrial DNA mutation has been well studied in China. Researchers attribute at least 33-59% of aminoglycoside ototoxicity to this change, according to studies from China.

That being said mitochondrial DNA is not always inherited to a disease causing level. In addition the authors point out the other problems"Genetic testing needs to be turned around rapidly, and consideration should be given to using an alternative antibiotic until the result of genetic testing is known."

The Sherpa Says: Well, no surprise. If there are charlatans in the medical genetic testing world where we are regulated, then imagine how ripe the field of ancestral testing is (Especially, given the lack of regulation). Let the buyer beware.....and hold the gentamicin please. Oh, and I am sick of watching the Myriad ad during Regis and Kelly!

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.

Want Longevity? Quit smoking and eat less.....

Yes, quitting smoking and eating less can help you. But it turns out some people will have an easier time doing these things. Also of note we begin to prove Murphy's Hypothesis (There is no such thing as a mongenic disease) These recent genetic studies caught my eye last week.

The first of this is sentinel study (Warning, all sentinel studies require replication)
This study reveals that patients with changes in the Cytochrome P450 enzyme 2B6. It turns out that"individuals with the CYP2B6 6 allele of the gene benefited from bupropion treatment and maintained abstinence longer while doing poorly on placebo, with a 32.5% abstinent rate vs. 14.3%, respectively. In contrast, those in the CYP2B6 1 group did well on both bupropion and placebo, with similar abstinence rates at the end of treatment and after a six month follow-up"

True that we do need some replication on this one, but there does seem to be other literature indicating this trend and other polymorphisms in Dopamine Receptors as well.

In addition to this one an article came out in AJHG this week. I want everyone to give up these words "MonoGenic Disease" Why? There is no such thing as a monogenic disease, unless you only have ONE GENE in your body. An example of this dichotomy is seen in the MONOGENIC DISEASE Hemochromatosis (Which BTW is not monogenic)

Unfortunately most Hemochromatosis is caused by mutations in HFE, but despite this testing, there are still people with Iron Overload who do not have HFE mutations. This is why I am not an advocate of HFE screening or even DTC testing of HFE. Even crazier, different people with hemochromatosis present differently. Why? Because there is no such thing as a MONOGENIC disease!!! In the AJHG this week an article shows that common variants in 3 other genes affect the penetrance of hemochromatosis. These genes are BMP2, BMP4, and HJV.
Serum ferritin levels were all affected by these common SNPs.There was even some indication of synergy between genes. To translate-Hemochromatosis is a multigenic disease, which primarily has problems in the HFE gene. So now is that clear as mud? The point....Don't expect a DTC test for hemochromatosis to tell you 1)If you will have Iron Overload 2)How bad your disease will be.

Finally, before you fall asleep or your heads explode, I want to chat about longevity. Some people think longevity can be bought with hormones, others with vitamins and Nutraceuticals (actually there is better data here). One big group thinks that all we have to do is stop eating.

This starvation group has recently been vindicated by studies on a family of genes called Sirtuins. A recent review was written in the Annals of Medicine. But just a couple of days ago an article in Cell the guys from Harvard Path publish on the role these genes play. Warning. This is a science heavy paper and the clinician may not find it useful at all....Dr Hsien Lei actually posted on this article as well. I see this as a potential windfall for companies looking to create Sirtuin activating cereals..........

The Sherpa Says: Gene Genie is up at Neurophilosophy so check it out! I am tuning up to host the next! We have along road ahead of us.....I like the way we are headed. However, there are some big bumps and changes coming up. Let's all keep our eyes on the prize...Truly Personalized Medicine

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.

Pilot study...Buy Stock in Kimball Genetics now!

On Friday I was picking on what I term haters of Personalized Medicine. You know those people who just shoot down the idea because of several reasons

1. Negative articles get print (contrarians always get published)


2. The doubters often have no genetic training (or combined with internal medicine) and are afraid of what they may have to do if Personalized Medicine succeeds (Which it will)


3. Their idea of Personalized Medicine is the snazzy websites of certain whole genome analysis, DTC testing or nutrigenomic fly by the night companies. Which are BTW putting a horrible stain on the name of Personalized Medicine. Francis Collins recently said "over promising can often kill a movement" so stop it. Or at least don't over promise. Please, I beg you.

Recently an article was published in the Journal of Family Practice. I won't link to it because, frankly it is a review which is skeptical, pragmatic, and clearly was written by someone who doesn't travel in the personalized medicine circles.

Why? The authors said that there is no clinical utility literature regarding the newest FDA recommendations for coumadin metabolism genotyping. Well......they were wrong. Perhaps they haven't heard of Harvard's CROWN study or this recently published article in the journal Blood.

I would like to analyze the article and first state that validation is the corner stone of any algorithm study. Well.......that too is coming soon. So before we have wise guy commenters on this study, please know that there is always a validation study in the hopper by the time an algorithm gets published.

So this study was performed on orthopaedic patients having knee replacements or revision surgery (I can hear the Cardiologists already.....well, that's not atrial fibrillation) Hold your horses, that study is coming.

The mean age for a patient was 58 years, with a range of 21 to 83 years and median of 59 years. Pretty close to the average warfarin user.

So what are the limitations let's let the authors speak.....

"this study has other limitations. First, our study population consisted entirely of patients initiating warfarin for deep vein thrombosis prophylaxis following total hip or knee arthroplasty. The ability to generalize our model for other indications is unknown and should be studied in a broad population. In particular, the appropriate starting doses and the ability to safely initiate warfarin without genetic information need to be examined in other patient groups—including nonsurgical populations"

The Sherpa Says: Well, this will be the first of many studies analyzing algorithms. Do I think it will be worthwhile? Absolutely. The end point was the therapeutic warfarin dose. They defined therapeutic dose as a dose that gave an INR (blood test indicating thinness of blood) in the target therapeutic range after 7 consecutive days. They managed to establish an algorithm which matched needed dose to approximately 80%. Which is more than I can say for the average Internist who may not even know the average dose based on ethnicity. So I await the validation but refuse to say there is no clinical utility literature. So to both extremes I say "Stop hating on personalized medicine and please stop over promising. If you both can tone it down, then we can get somewhere....safely" Oh and BTW for you VCs/Investors/Hedge Funders out there, Kimball Genetics has an FDA approved genotype test for warfarin metabolism........

Tip60 tips off breast cancer aggresiveness

According to a study published today in the journal Nature shows that a gene called Tip60 is involved in the development of breast cancer. But more importantly.........reduced expression of Tip60 protein leads to more aggressive tumors. Tip60 is a tumor suppressor gene unlike others.....

Let me explain. Usually you are required to have both copies of a tumor suppressor gene affected to start developing tumors. I feel that this theory along with all things mendelian will start to fade away. Why? Because we are much more complicated that punnet squares. The field of systems biology is growing and we will soon realize that we are a complex interactome, not just autosomal/Xlinked/Ylinked dominant/recessive genes.

So where were we? Well it turns out that this tumor suppressor gene only needs one copy malfunctioning to start enhancing tumor growth

From the Primary Investigator Dr Tim Crook "More aggressive types of breast cancers tend to recur after treatment, spread to other parts of the body and respond less well to chemotherapy. The identification of Tip60's role in breast cancer is a step towards predicting the aggressiveness of the disease and then individualising chemotherapy for women. If we can transfer this knowledge to the clinic, it could have dramatic effects."

From the Study

* Activity of the Tip60 gene was found to be lower in nearly half of all ductal breast cancers studied (21 of 52 cases) and in 17 out of 20 of tumours classed as 'high grade'

* The amount of TIP60 protein was studied in an additional 179 breast cancer samples. In almost three quarters of these (129/179), there was no TIP60 protein present in the cells' nucleus - in healthy cells this is where most of it is located. The proportion of cancers lacking nuclear TIP60 was even higher when they singled-out aggressive cancers and early cancers - suggesting that this is an early event in breast cancer development.

The Sherpa Says: Personalized medicine is coming and in many cases it is already here. This is an example of tumor tissue sampling to analyze outcomes. What is truly needed is a tissue bank that can put phenotype with genotype. Then we can have an excellent expression array analysis combined with phenotypic markers. This is the best way to put together personalized oncology. Trust me it is coming. Soon.....

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.

Oscar and Predictive, Personalized Death

I just had to post on this today. In the New England Journal of Medicine there was a brief article on an Uncanny ability by a unique cat.

From the article:

Oscar takes no notice of the woman and leaps up onto the bed. He surveys Mrs. T. She is clearly in the terminal phase of illness, and her breathing is labored. Oscar's examination is interrupted by a nurse, who walks in to ask the daughter whether Mrs. T. is uncomfortable and needs more morphine. The daughter shakes her head, and the nurse retreats. Oscar returns to his work. He sniffs the air, gives Mrs. T. one final look, then jumps off the bed and quickly leaves the room. Not today.

Making his way back up the hallway, Oscar arrives at Room 313. The door is open, and he proceeds inside. Mrs. K. is resting peacefully in her bed, her breathing steady but shallow. She is surrounded by photographs of her grandchildren and one from her wedding day. Despite these keepsakes, she is alone. Oscar jumps onto her bed and again sniffs the air. He pauses to consider the situation, and then turns around twice before curling up beside Mrs. K.

One hour passes. Oscar waits. A nurse walks into the room to check on her patient. She pauses to note Oscar's presence. Concerned, she hurriedly leaves the room and returns to her desk. She grabs Mrs. K.'s chart off the medical-records rack and begins to make phone calls.
Within a half hour the family starts to arrive. Chairs are brought into the room, where the relatives begin their vigil. The priest is called to deliver last rites. And still, Oscar has not budged, instead purring and gently nuzzling Mrs. K. A young grandson asks his mother, "What is the cat doing here?" The mother, fighting back tears, tells him, "He is here to help Grandma get to heaven." Thirty minutes later, Mrs. K. takes her last earthly breath. With this, Oscar sits up, looks around, then departs the room so quietly that the grieving family barely notices.

On his way back to the charting area, Oscar passes a plaque mounted on the wall. On it is engraved a commendation from a local hospice agency: "For his compassionate hospice care, this plaque is awarded to Oscar the Cat." Oscar takes a quick drink of water and returns to his desk to curl up for a long rest. His day's work is done. There will be no more deaths today, not in Room 310 or in any other room for that matter. After all, no one dies on the third floor unless Oscar pays a visit and stays awhile.

Note: Since he was adopted by staff members as a kitten, Oscar the Cat has had an uncanny ability to predict when residents are about to die. Thus far, he has presided over the deaths of more than 25 residents on the third floor of Steere House Nursing and Rehabilitation Center in Providence, Rhode Island. His mere presence at the bedside is viewed by physicians and nursing home staff as an almost absolute indicator of impending death, allowing staff members to adequately notify families. Oscar has also provided companionship to those who would otherwise have died alone. For his work, he is highly regarded by the physicians and staff at Steere House and by the families of the residents whom he serves.

The Sherpa Says: Perhaps this cat is just "sucking the breath" out of the patients.............

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.

Some times you don't need a genetic test.

Before I head home post call I want to talk about an important case I saw early this morning. I was in the emergency department admitting this poor gentleman who had developed something called angioedema. He had just started a new medication for his blood pressure called an ACE inhibitor. There is some thought that this reaction is brought about by a genetic predisposition. We do have examples of hereditary angioedema and the mechanism for this man's angioedema is likely very similar.

While seeing him and having the Ear, Nose and Throat doctor secure his airway with a cricothyrotomy (a hole cut into the neck to insert a breathing tube) an emergency room tech runs and hands me an EKG. He says "This patient is having a heart attack"

The hallmark findings of heart attack on ekg were indeed there, however there was something more. He was brought into the emergency department not for chest pain, but this 26 year old man came to the ED because he was involved in a bar fight and was drunk. He had a huge bump on his head. Normally the treatment for a heart attack is blood thinners like aspirin. If I hadn't looked at the EKG closely I would have given him these thinners.

No, what this young man had was not a heart attack. He had a condition called Brugada Syndrome (A genetic heart disease). This condition causes sudden cardiac death and placing an Automatic Intra-Cardiac Defibrillator can be lifesaving. Much more so than thinning his blood and risking a bleed in his head. But what would have happened if I didn't read the EKG? Brugada syndrome isn't rare (I saw 2 people with it last month) However, if you have not seen it. You can mistake the EKG for a heart attack. That would have been a costly error in this patient who did have some blood in his brain.

The Sherpa Says: If you have sudden death in your family, please go get an EKG. You never know what you might find. More importantly, what you might prevent. You never know when genetics will show up and the better prepared you are the better care you get. Even in an emergency, genes matter................

No More Skin Biopsies????

Imagine going to your dermatologists office and instead of getting biopsied for your funny looking mole, the dermatologist places a little sticker on the mark.

He sends it off in the mail and later that week you are told that it is just a mole....phew......

That is the promise of a new technique called EGIR or epidermal genetic information retrieval. A new company called DermTech has just developed the technique. So what is the technique and how does it work?

The tape collects RNA from the skin sample. The sample then was amplified as cDNA and a microarray checked for the 117 gene analysis. This technique was studied and a 5 gene profile was adopted and accurately differentiated melanoma from benign skin changes. This technique is being evaluated at University of California San Francisco.

The Sherpa Says: In general only 3-10% of suspicious lesions are actually melanomas. The traditional method to detect includes a scalpel excision.....Tape......Scalpel... You decide. However, this is only a small study that determined proof of concept. There is a replication study underway and despite being great for the patient, the dermatologist can't exactly bill for RNA extraction. They do get paid very nicely for skin biopsies though. Not quite for prime time, but it does demonstrate how ubiquitous genetic soon will be in the office.

Sherpa Posts Total 100!!!!

No I am not nearly as prolific as some of my contemporaries, but hey I have only been at this since March ;)

I hit the milestone of my 100th post today. In my championing, flaming, arguing, almost getting sued (Thanks San Fran!), and just plain out bashing quacks I have discovered some amazing people and some amazing sites. The following is a running tally of blogs I love. Some genetic, Some medicine, Some not so much.

• Scienceroll by Bertalan Mesko soon to be MD



• Bad Science by Ben Goldacre MD



• Eye on DNA by Hsien Lei PhD



• Highlight Health by Walter Jessen PhD



• Revolution Health's CMO Jeff Gruen MD



• The DNA Network and its littany of great blogs!



• Mashable the blog for social networks



• Buddhist thought by James Ray



• The Entrepreneurial MD



• Great Pics from around the World at Cosmos



• The latest and greatest at Science Friday



• The Wall Street Journal's Health Blog



• Wired's Science Blog



• NPR's On The Media
  

I know that this only 14 blogs but each is worth its weight in gold. It is Thursday and July so forgive me but I have to deal with some new interns :)

The Sherpa Says: Thanks to all of you. I look forward to the announcement when I hit 500 posts! Let's keep our eyes open and realize that there are a whole lotta people out there trying to oversell genetic tests. Or even worse. Knowledge is just a set of unorganized facts. Wisdom is knowing where to find the answer. I will strive to give you that answer or at least have the wisdom to find it.

Happy Independence Day US!!!!

The Sherpa Family Would like to wish all of you A Happy Fourth Of July!

Even for my friends from every country of the world. Take this day to remember everyone who fought hard to give us the lives we now enjoy.

-Take Care

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!!!

WBUR posts on coumadin and Personalized Medicine!

Despite the heavy Boston accent,

On WBUR Carol's worries regarding Coumadin and Personalized Medicine hit home to millions of patients everywhere. This is an excellent example of the press' coverage of my specialty. Dr Sam Goldhaber a physician at Mass General talks about the promise of pharmacogenomic testing in blood thinning and avoidance of its horrible side effects.

Lastly they interview the Pope of Personalized Medicine

Francis says "Is this the scenario we want personalized medicine to enter?"
"The public thinks that this is snake oil (i.e. Direct to consumer testing and nutrigenomics)"

In addition Dr Collins talks again about the 2 Betty's and the potential to miss diagnose and have horrific outcomes.

The Sherpa Says: "Save Betty!!!" We must take the time to educate everyone about the promise and pitfalls of personalized medicine. In My Humble Opinion, the only thing to move physcians will be the slew of lawsuits that happen after we publicize our great outcomes at Helix Health of Connecticut.