About Helix Health of Connecticut.

Well, I have been getting alot of questions regarding our personalized medical practice on Park Avenue in New York City. I have been reluctant to tell everyone, but I figure that I might as well let everyone in on our "secret"

My philosophy is the power of genomics should empower patients and providers. Together as a team we can prevent some horrible diseases and avoid some horrible adverse drug reactions. How do we do this? We take the skills from a multidisciplinary team and identify risk. We feel that the most powerful genomic tool out there is family history (Sorry Hsien). This has been validated over and over again in epidemiological studies.

In fact when Mike Leavitt indicate in his foreward of his Personalized Health Care report

"One part of the foundation for such a change is our rapidly growing understanding of the human genome and the processes it directs. We envision health care that could:

• predict our individual susceptibility to disease, based on genetic and other factors;
  



• provide more useful and person-specific tools for preventing disease, based on that knowledge of individual susceptibility;
  



• detect the onset of disease at the earliest moments, based on newly discovered chemical markers that arise from changes at the molecular level;
  



• preempt the progression of disease, as a result of early detection; and
  



• target medicines and dosages more precisely and safely to each patient, on the basis of genetic and other personal factors in individual response to drugs. "

I thought he had read our business plan. But then I realized, anyone with an insider view would have to conclude the same thing. This IS personalized medicine. I think that the fields we will see explode are services which Helix Health of Connecticut is offering.

The problem I have always had with academic genetics is 3-fold.

1. Most geneticists are pediatricians (8 in 10) and have not been trained in adult chronic diseases or even used most medications that are intended for adults.
   
2. Traditional genetic care offered in the "Ivory Towers" is diagnose and adios. They have no desire to offer close follow up. In fact, in the time that I worked at an academic center we did very little to recontact those difficult clinical genetics cases. Only metabolic patients get the close follow up needed.


3. There is NO privacy at a big center. In most places you are pushed through like a means to an end.
   

The last problem I have with traditional genetics lies in how we acquire medical information.

In a clinical genetics appointment of 45 min to 1 hour you get a fam hx from the genetic counseling student which takes 20 minutes, they attempt to take a medical history (despite having no medical training), they then present to an attending or fellow (10-20min), who then comes in a confirms the information. Now with 15-20 minutes the attending has to explain complex genetics and inheritance to you, send off subtelomeric, CGH, karyotype, genetic tests, etc. And you get ONE follow up appointment and may wait 6 months for another appointment.

In a cancer genetic situation you do have more time. Perhaps if your counselor is good, you get adequate follow up and acquisition of information. You may be seeing a geneticist (Who has not trained in adult oncology) or you may be seeing an oncologist (Who never trained in genetics) If you even see a physician at all. This is not to knock my CGC friends. They have truly great talent and training, but learning what to do with your Plavix is not one of them. In fact our head counselor said "When I took a family history and it looked like there was early heart disease I said to myself 'I know something is there, but what do WE do about it?' Therefore the problem lies in the training or perhaps in the team.....

And please do not get me started with the Chop Shop known as "prenatal genetics/high risk OB clinic" Where the standard is to get as many people as possible into and out of the counselors office and the into and out of the amnio as quickly as possible. Where is the CARE in that? Is there any PRE-Conception care out there? There is at Helix Health of Connecticut!

What kind of medical informatics system is employed at most academic centers? Archaic at best in most. At least where I and my partners have been. When even the highest powered EMRs cannot distinguish between maternal or paternal lineage, then you have a problem. We have developed our own.....

Lastly, where is pharmacogenomics? Where is chronic disease risk stratification? Oh I forgot, geneticists don't do this, nor is there training for this in classical genetics fellowships.
All of this and more is available in my vision of what personalized medicine should be. Helix Health of Connecticut is Personalized Medicine for the 21st Century(TM)

The Sherpa Says: Helix Health of Connecticut of CT is my dream, my vision and the tip of the personalized medicine spear. I know this may seem like an advertisement, it is not. It is the road map which all personalized medicine practices should follow. When you take Prediction, Prevention and Privacy to the highest standards of care, you are bound to succeed.

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.

Can you fix the typos????

The Sherpa would like to thank all of the readers who have tolerated the foray into mobile blogging that I have undertaken. I have had a few posts which have been hard to read as well as full of typos. Lately given my schedule I have had little time to revise these. I will take more time from now on I promise.

Now Back to some interesting stuff!!! Recently in The Journal of the American Medical Association a study was published linking Coronary Artery Disease and Colorectal Cancer. Why am I, a gene guy, posting this study? Several reasons, but first let me talk about the study. Patients in Hong Kong were recruited for screening colonoscopy after cardiac catheterization (a procedure where they look for disease in your heart blood vessels.)

Right there I think I several confounders. Aspirin can reduce colon cancer occurrence in some types of patients, Statins (Lipitor et al) have been portrayed by pharma companies to prevent cancers (Although the Sherpa thinks the opposite....) in addition what about prior colon disease????? All of these things were controlled for. But what wasn't? Family History of colon cancer, it wasn't even checked.

That being said, the results are interesting simply because there have been smaller studies linking and refuting the link between CAD and Colon Cancer. In this very large study where they controlled for several factors in this chinese population, the Odds Ratio of Colon Neoplasm and CAD was 1.88 more worrisome, if you had Colon lesion and you have CAD your OR for an advanced lesion is 2.51 YIKES!!!!

Now the real question......Why? The authors identify inflammation as the culprit. Inflammation is known to be a risk factor for CAD as well as Colorectal Carcinoma. Perhaps these hyperinflammatory people are getting hit with both. Well, I would say that is pretty reductionist. What I would like to propose.....Every person who enters any study in the US or even any country, Everyone gets their DNA sample taken. We knock down the barriers to getting this information and then we really find out what's going on in these susceptible persons.

That's why the Broad Institute has started this amazing project called the Connectivity Map. What is a connectivity map? It connects the dots by analyzing gene expression patterns. Led by Todd Golub, this team is pretty amazing. MedGadget posted on it last year. I am surprised it hasn't gotten more play. Maybe this will help us find out what's going on with ASA and heart attack or even colorectal cancer.....

The Sherpa Says: I am curious to know what all of you think about getting to: knowing what's wrong, why it's wrong, why the medication to treat it works, and who it works for. I know for one that I am

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

Scientists and The Sherpa Urge Caution

According to a recent post at Medical News Today a new article will be published in Science urging caution with the availability of genomic sequencing. I have commented on it several times and now feel like we are beating a dead horse.

Listen, if you want your genome to help you decide what clothes to wear, or perfume, or as a trophy. Then go out and get one. I will never stop you from getting your genome as a novelty. But if you want to use your WHOLE genome to make healthcare decisions.......... Well, you better get a second opinion. The only genetic testing that will work for healthcare has nothing to do with whole genome analysis.......for now. So why get your genome? Because, if you get it once you never have to do it again? Well, you saw how that worked out for the iPHONE right?

On a lighter note, as I sit here in the ICU taking care of really sick people I am left to think....What if we could prevent chronic diseases? These are the diseases which once end-stage put you in the ICU. Where I now sit taking care of end stage heart and kidney disease. That is where the power of the genome lies.....in prevention.

The Sherpa Says: Early adopters are wonderful. The world would not advance if it weren't for those who challenged conventional wisdom. But when it comes to human life........well, I am not ready to "crack a few eggs"

Just saw the BRACanalysis Ad on ABC 7

First off, please vote on my site. "How Much Would You Pay For Your Genome!

For those of you who live in the Greater New York Metropolitan Area. You are in for a treat! I just saw the confusing, puzzle like ad for BRACanalysis (The BRCA tests by Myriad)

Do you remember those tile shifting puzzles where you have to move all the pieces the right way to get a clear picture. This is actually a perfect metaphor for this ad. It shows women of every race and age all in blocks. The boxes look exactly like the aforementioned puzzle.

Each woman says a different thing and they all blend together. From "My mother has breast cancer" to "my father's sister has breast cancer" they make it seem that all breast cancer can be detected by this test. The commercial states BRACanalysis B. R. A. C. "Be Ready Against Cancer" Too bad they don't give their aunt's age, and no one says "everyone in my family has breast cancer" This ad portrays sporadic breast cancer as an indication for BRCA screening.

This paper describes the past ad campaign. My gut says this is the same as before. Guerrilla marketing does state that you do have to be consistent and have commitment to be successful. SO IF AT FIRST YOU DON"T SUCCEED.......

This type of advertising creates an opt-in, directing you to the website BRACnow which is actually a pretty useful site. The problem I have is when you are searching for a provider. They list several physicians who have not had cancer genetics training. Which is ok.....if you have a NEGATIVE test. But what if you have a Variant? Also my question is....... why are there so few genetics providers in the Tri-State Area? I know my group at Helix Health of Connecticut can do these services, but where are the other providers?????

The Sherpa Says: Here it comes New York.....I hope you are ready. Too bad most NYC genetics providers are booked for 6 months in advance......

Thank You

Today I received a phone call that made my month. One of my wonderful readers called and said "I love reading the Sherpa everyday! You have some way of fitting in really interesting and insightful information that I don't get anywhere else. Trust me, I am on the Internet all the time. No one has this stuff but you! So keep it up Sherpa!"

Let me tell you a little bit about the Sherpa and his (my) day. I usually get up around five am. I hit the snooze button but it never seems to work. Mainly because my daughter has decided to get up as well. I get the baby, change the diapers and turn on the computer. These days I turn on the Treo 700wx as well. I see what emails have transpired while I was sleeping and I get an invoice from my employees overseas.

My S.O. heads to work and I am left alone with my extremely vigorous child. I feed her the bottle while checking the DNANetwork as well as turn on the "news" (what I mean here is the propaganda machine run by PR specialists)

I usually field 2 to 3 phone calls in the morning from my residents. They tell me about how things went overnight in the hospital. Then I hit the shower (yes, even Sherpa's shower)

When I get out, my RSS feeder has finished updating and my daughter has had enough of the PnP (pack and play).

I feed my lovely daughter her bottle and scan the RSS while she is eating, making notes on my Treo. I then take a 5 minute break to give her TOTAL attention. It's 7:15 am, then the phone rings, it is the sitter. I buzz her in (Thank God)

Then the day begins.....I won't share more here. But let me tell you, that part of the day has been a breeze so far.

So I want to thank all of you who read the Sherpa. I appreciate all of your time and attention. Today I want to put something out there for your digestion. AlterNet has posted on something that had worried for sometime (see here). I don't mean to upset the well intentioned people at Google (They are ALWAYS the biggest viewers of The Sherpa according to feedburner) but there are some significant concerns that medical professionals have. Now it is getting some significant play.

Google has been in the info gathering game and has been doing it very well. Unfortunately HIPAA came along and I think the guys in Mountain View have bit off more than they can chew. Do you have any idea how expensive EMRs are? I chalk it up to the HIPAA and billing code abilities that an EMR must possess. Privacy is a big issue even if GINA passes (which it will). GINA does not cover life insurance, secondary schools, potential mates.....etc

The Sherpa Says: I thank you all for listening to my morning. I hope you find as much enjoyment in reading the Sherpa as I do posting it. As for private information moving out of your control, whether you are a utilitarian or an autonomist you have to admit there is something fishy to this type of power grab.

Media Hype in Genetics??? Blame the Geneticists

First, I would like to say thank you once again to GTO.

A recent article published in Nature genetics reviewed some research done by Bubela & Caulfield. This study indicates that the journalist "hype" was actually in agreement with the original source's "hype". The story entitled "How geneticists can help reporters to get their story right" is also covered at Uncommon Ground




Scientists have a social responsibility to talk knowledgeably with reporters, and to do so is in the interest of science in an era when public funding and control over science is significant. However, some scientists avoid this task because it is onerous. At a minimum, it requires the same level of preparation that one would give to a platform presentation at a scientific conference. Such time and care are warranted, because the reach of the reporter is larger than that of the academic conference.





Well, I wonder if when pressed for a deadline, the journalist will rely on the press release written by the company/institution/PRrep.Or perhaps they will take the time to track down these scientists and physicians.....Maybe a savvy journalist can help me. Misha????






The enthusiasm of scientists for their work can feed such hype (as can the demands for grant funding). For example, in 1993, medical geneticist W. French Anderson predicted that soon, “…any physician can take a vial off a shelf and inject an appropriate gene into a patient.”18
The enthusiasm for the prospects of gene therapy among some members of the
scientific community drove a tidal wave of optimistic reporting that suggested a 10-year
time frame for gene therapy as practically cure-all. The optimism was immensely
overstated, at least for the time period for which it was predicted.





True enough......Maybe we do have to quote Pogo





The Sherpa Says: As long as scientists and journalists want to hype, I will be there to debunk. Just for you. Oh and by the way, MikeLeavitt and the HHS has just posted their report on Personalized Healthcare Prospects. The future, its here.

Personalized Medicine Creates Personalized Injury Attorneys

This excellent article written by B.J. Evans enititled Finding a Liability-free Space in Which Personalized Medicine can Bloom. points out some new potential areas of litigation that physicians who practice personalized medicine will be subjected to. I think that this article raises some good concerns and I advise all physicians looking to make the jump into Personalized Medicine read.

Interesting points included

1. There is no litigation precedent for failure to identify non-responders. There is a well defined system for adverse drug reactions. But what happens if we detect injury at a molecular level? I don't remember ever seeing a lawsuit for mildly elevated liver enzymes with a cholesterol lowering agent. But could there be? I would say that is a detector of drug injury. From the article:

Consider the hypothetical question, ‘‘Would you refuse to prescribe a drug
if a screening test predicts that the patient will be a non-responder who will not benefit from the drug, but not be harmed by it? Assume no alternative therapy is available
and the patient expresses a strong desire to attempt treatment with the drug.’’
Many physicians indicate they would be fairly likely to acquiesce with the patient’s request to try the drug. Similar acquiescence is seen in studies of how direct-to-consumer drug advertising affects prescribing decisions.

Interesting the same effect is seen in genetic testing. Which is why Myriad is shelling out for the campaign. Despite older studies showing that testing was not increased back in 2003. They hope that the newer data holds true. We'll see.

2. There is only a small risk of being sued if a drug demanded by the patient proves ineffective. There is a greater perceived risk of being sued by a patient whose condition worsens after a strongly desired treatment has been withheld. I personally know that this is an objection by several practitioners I have spoken with. "Why put myself out there?"

3. A few states do treat drug labeling as the standard of care, but many states treat it as just one factor to consider (see ref. 19, y7). Being the first to embrace a new technology carries risk, if there is no clear regulatory standard for courts to apply, and if the professional standard of care is mired in traditional practice. Today’s malpractice rules reward conformity, placing individual physicians in a poor position to lead the charge in applying efficacy biomarkers.

4. Clinical translation of pharmacogenomics may ultimately be a long, phased process that begins in niches where favorable legal conditions can be found. ERISA provides a favorable
niche that may make insurance reimbursement decisions the initial locus of clinical translation.

The Sherpa Says: This is an excellent written article illustrating the unknowns out there. I feel that there is even more out there that are "unknown, unknowns". While we are moving at light speed towards a personal genome, we need to step back and think about all of the legal implications that we may create.

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.

Thanks to Dr Bettinger

I would like to thank Blaine over at Genetic Genealogy. He brought up a good point that I decided to clarify. The good folks over at Genome Technology Online thought so too.


September 14, 2007
Slow Down, and Mind the Gap

At Gene Sherpas: Personalized Medicine and You, Steve Murphy writes that overselling genomics could ruin the promise of personalized medicine. He defines the "gap phase" in between genomics and medical application of genomics as having "to do with literature and evidence based medicine. In medicine, doctors try not to do anything without good data that shows long term outcomes." The problem, he writes, is that there needs to be more physicians trained in genetics, or more geneticists available to them to interpret all that new genomic data."

In reading the link, I realized that several members of the DNANetwork have been quoted. I am so glad that we have this wonderful group. Even though we all may not agree, all the time. I think we all can agree that to get the best information on the bleeding edge of genetics, health, and science all you have to do is tune in to the network.

Lastly, I wanted to make a plea for Bertalan Mesko over at ScienceRoll. He is looking for donations to have his genome sequenced. I only can imagine the ebay implications........ If you thought auctioning off your baby's name was unique. Wait till they start auctioning off genomes!!!

The Sherpa Says: Berci, Helix Health of Connecticut will pay for your genome once the cost is 1000 USD. Although we don't recommend using the WHOLE genome for healthcare decisions quite yet.

Up To Date meets Illumina!!

If you aren't aware of what UpToDate is, chances are you are not alone. But if you are a physician, I am certain that there is no way that you have not heard of this valuable resource. This website was originally conceived of and designed by Burton Rose and has revolutionized medical practice. For a subscription fee you get access to articles written on almost any subject of medicine (Very little on genetics though)

It allows physicians to practice on the fly Evidence Based Medicine. It is very informative and worth the subscription fee.

Imagine if there was a genomic resource which would allow physicians to translate genomics into the practice of personalized medicine. My answer is.....soon such a tool may exist. I have just finished a brief conversation with the physician who may be the next Dr Rose.....

I can't reveal much without his permission. But that gap we're minding may just be closing a little bit!

An Attorney General, A Genetic Counselor and Gap Phase

Today my phone blew up. I had five different Venture Capital firms call me to pick my brain about "The New deal with Illumina" as well as "Viability of Microarrays in Pharmaceuticals"

I must say thank you to those who called. I look forward to speaking with each of your esteemed groups.

That being said......I must say that there is a general consensus of the physician side that the time for whole genome analysis for your health is not now. I agree. An excellent scientist Dr Bettinger over at the Genetic Genealogist posed a great question.

"What is your opinion on Gap Phase?....."

"that inevitably long period of time between (1) the availability of inexpensive whole-genome sequencing, and (2) the point when the medical field produces enough specialists in genetics to handle the work load."

Well....I don't think that is what gap phase is. Currently there are less than 1300 geneticists for the WHOLE country. In addition. If we expect personalized medicine to affect things like Coumadin, a drug which is dosed by adult doctors primarily, then shouldn't we have some adult geneticists? There are less than 100 of these doctors in the US. LESS THAN 100!!!!!!! Even scarier, there were less physicians sitting for the genetics boards this year than 5 years ago.

I don't think Gap phase has anything to do with these people. I think GAP phase has to do with literature and evidence based medicine. In medicine, doctors try not to do anything without good data that shows long term outcomes. When they veer from this path you get train wrecks like drug eluting stent mishaps and Vioxx!!!! Soon to be Avandia!!

So what do we do with the gap? We mind it!! We don't jump blindly without looking out for the fall that it may cause. Overselling genomics could destroy personalized medicine's promise! I will not let some overzealous "Let's do it because the technology is there, and so cool" people ruin our future. Even for a quick set of chromosomes!

As for trained professional shortage....When we have fighting between lab companies and the people who traditionally order tests, then we have a problem. Which is the case with Myriad.

There is a great NPR spot coming up. A colleague and teacher of mine Ellen Matloff. She will be on there with Attorney General Richard Blumenthal discussing the controversial Myriad advertisement campaign that is now running in CT, MA and NY. You can listen in online Sunday Evenings at 6:00 PM http://www.wnpr.org/

Ellen is the bane of Myriad's existence and because of this the genetic counselor is notably absent from the Myriad commercials.....hmmmmmm

She has started an online petition to start asking state's attorney generals to investigate misrepresentation in genetic testing. My genetic counselor has a wonderful take on this whole thing. BRCA testing is NOT in Gap Phase, unlike whole genome sequencing for healthcare. It has significant amounts of data and studies. It is clinically useful and can be of benefit when used properly. The problem.....The Fox is watching the Hen house. Lab reps are probably not the best people to be teaching physicians about using these tests, trained counselors and Geneticists are.

I am scared for physicians and this should serve as a warning call.

MYRIAD/23andME/Navigenics/futureunnamedbiotech are saying, "if you aren't with us, then you're against us, AND WE WILL REPLACE YOU WITH COMPUTERS!!"

The Sherpa Says: When my phone blew up today, the question was not, how can we invest in a safe product and service that will benefit people's medical care. It was..."How can we make this scalable?"......The answer does not lie in training genetics professionals....that takes at least 9 years after college. The Answer......All roads lead to Google.......Too bad the data is not there and computer guys haven't been burned as bad as those Vioxx doctors......

NYT and WSJ cover Myriad's campaign

I have been silent on this for too long. Why? I was awaiting the review by my attorneys. The last thing I need is another threat of litigation. Why litigate? Because, critics like myself and the esteemed Ellen Matloff from Yale :) have been telling physicians that testing for BRCA ain't like checking a sodium.....or even better a pregnancy test.

Why can you get a pregnancy test over the counter? Because its results are crystal clear. The FDA has requirements for OTC testing. This whole issue was raised with at home HIV testing. The issues were portrayed here.

The interesting questions poses include these.

What test characteristics favor possible approval of an OTC home-use HIV test?

• The test is simple to use compared to other types of HIV tests and earlier versions of rapid HIV tests, suggesting that untrained persons will be able to perform the test properly.
• The test does not require special storage conditions.

The most interesting one was......

• Informational materials supplied with the test are sufficient to provide adequate information to potential users on performing the test and to substitute for live counseling.

Now my question is....has it even been proven that written materials substitute for adequate face to face counseling? Never for BRCA testing. So why does it take evidenced based medicine to prove a drugs efficacy? Well, partially because the FDA's evaluation is not about efficacy. It is about danger to the patient. Is there danger in not getting cancer screening if your BRCA test is negative? (Which BTW is not an appropriate counseling answer to the patient)

Yes, I do agree with Hsien. Direct to consumer advertising is a great way to introduce new products. Like the iPOD.

"Advertising serves to bring new products to our attention and to stimulate interest as well as the desire for more information. In the case of genetics and genetic testing, I would venture to say that all of us need to learn more, not less."

But the best way to learn about breast cancer risk is by being able to ask question to a knowledgeable, trained, health professional. How do we learn more about genetics? Take a freaking class, don't try to do self counseling for G-d Sake. Has anyone seen the Edward Jones commercial where the surgeon is telling a guy sitting at his kitchen table how to do surgery? Over the phone the surgeon asks "Did you sterilize the field?.....Good now with your kitchen knife make a 3 inch incision.........."

This is the type of thing that DTC testing is trying to get you to do. Patient empowerment aside, I don't let my patients prescribe their own meds. I even guide them on vitamins that they take. Did anyone see the expose on the Vitamin Shoppe's vitamins containing abnormally high amounts of lead. It was on Good Morning America a couple month's ago.

Well as the post was entitled the NYT and the WSJ had article on this yesterday. The ad campaign is telling you to go see you internist, OB/Gyn, or family practitioner. Guess what none of them have had training regarding this topic. There are less than 100 internist/geneticists in the country and even fewer OB's and FP's. According to the WSJ

Myriad says it is developing a program to school primary-care doctors about the test. Dr. Critchfield said the company is focusing on primary-care doctors, oncology specialists and tertiary-care centers, along with genetic counselors, "to get the message out."

What struck me was the benevolence of Dr Critchfield, who in the NYT article

Dr. Critchfield said Myriad waited nearly five years to start the new campaign to give more time for health care providers to learn to handle genetic testing. “We are in a far different place today than we were then,” he said.

The Sherpa Says: Well Dr Critchfield, you are incorrect. Clearly he has no clue or doesn't want to sour the internists' palate. OB's regularly fail to recognize at risk and not at risk groups, so do internists. As for the newest batch? I just tested primary care residents at a major academic center and only 30% recognized that a BRCA test was NOT indicated. Maybe that's what Myriad is looking for? If you want the literature I have quoted, send me an email and I will be more than happy to forward it on. As for the 8 month wait, Helix Health of Connecticut is open for business and seeing patients in less than a month!!!

Gene Genie and George's Blog

First....Gene Genie is up at Cancer Genetics. Thanks to Ramunas who put up an excellent edition!!

Second and even more importantly......My excellent Chief of Genetic Counseling brought George Church's blog to my attention. My gosh....

His evaluation is right on point. His question is a wonderful one...... Great now we have genomes....so what. How do we get to systems biology? Once we have systems biology on point, we will then have truly personalized medicine. We will be able to manipulate the systems....and physicians will become engineers, systems analysts....

So when will we get there? How will we get there? My gut says there are 25 different signalling systems and perhaps four different common pathways....these will corroborate with the 4 humours........ Welcome back Galen and great to see you again Hippocrates.

The Sherpa Says: Stick around for 2010 it's gonna be huge! I am a firm believer in systems biology. I feel that be understanding cellular signalling pathways, we will see the link between previously unrelated disease. For an example if this take a look at this NYT article.

Genomics as a Lifestyle

As I watch things such as the wonderful Personalized Genome Project, The Personal Genome Education Project, 23andMe and all sorts of venture capital lining up to hit the "cash cow" known as the genetic lifestyle. Hsien over at Eye On DNA has been posting on this for quite some time. This one takes the cake.

This is much more than Personalized Medicine. It is the economic equivalent of the "Organic" movement on bovine growth hormones :)

Why? I would like to name 3 reasons

1. Organic healthcare sells to a group who go outside the "mainstream".....But genetics IS soon to become mainstream, unlike Organic/alternative healthcare, which took almost 50 years to gain acceptance

2. Organic Foods can now be shifted into Molecular foods. This allows them to position as Nutrigenomic Foods. Not to mention the fact that the manufacturing infrastructure required to make nutraceuticals is already in place.....clearly bioactive compounds will allow your genetic predisposition to be tweaked.

3. Personalized nutrition, workouts, etc..., just for you, Google already knows and is starting to cash in on the next wave.....Personalized everything.

My only concern about this living style is that we start discriminating because of predisposition....

But clearly we are headed to an age of genetics as lifestyle.....even before the literature will bear it out.

The Sherpa Says: I can only hope that this can enhance our lives and not just lighten our wallets. P.S. Dr Mishkin has sent me Salugen's data......stay tuned

LRP8 and Familial MI....Ho Hum

This month in the American Journal of Human Genetics we have some interesting publications. Including an association study identifying a gene known as LRP8. So what is LRP8? It is a receptor for bad cholesterol. When bad cholesterol binds this receptor, platelets (the bricks in your blood that build a clot) become sticky making it easier to thrombose (form a clot).





I am interested in this study for several reasons. First, it has been shown that platelets get stick even after ingesting a Big Mac. That's correct. Just one fast food hamburger can theoretically precipitate a heart attack. So naturally we would love to know who. Think Personalized Diet/Nutrigenomics. I wonder if Salugen can hear me now? I still haven't received their "Scientific Data" yet. I will publicize it if they do.





Back to the study. So what was studied is a group called the GeneQuest families of familial MI, the control group was some white men who were given cardiac catheterization and found to have no atherosclerosis burden (OOPS). Well, that control does not mean they did not have atherosclerotic burden, because catheterization cannot identify 30% occluded vessel plaques.





In addition their findings were replicated on an Italian cohort of familial heart attack as well. So why do I say Ho Hum?





Let's see: No Odds Ratio was greater than 1.43 This 43% increase in heart attack and coronary artery disease is still less than the family history risk itself. The only good thing was that this risk persisted even when controlling for plasma total cholesterol levels, triglyceride levels, hypertension, and diabetes, in addition to age and sex.





What is your odds ratio for heart attack if your father had one prior to 65?


The Answer: 5.8 according to Maren Scheuner's article on familial risk for MI.





Do you now see why I say HO HUM about this gene? When will we see the gene card panel for MI??????

The Sherpa Says: Listen to all of this hulabaloo about Ventner's Genome. Even Men's Health magazine says you should bank your parents DNA if they die. What good is all of this if we don't have a key to the map? The map will make no sense! LRP8, APOE4, I could go on and on. What good is a genome map, without a guide? What good is the guide without the studies? Why did you buy the iPOD early, only to have late adopters get it cheaper? For the rebate? Doubtful. This is why primary care physicians are late adopters. If you want to get your genome (and I do) then you better be prepared to find someone who will help you understand it...becasue cliff notes, or Navigenics just won't do. Nor will scarfing down Big Macs....

1000 Genomes???? Coming Soon.

I have been looking at the genome of Craig Ventner. What Surprises me is that we haven't do this sooner. If you haven't heard the diploid genotype of Craig Ventner is up. And several of my buddy bloggers have posted on it. Blaine posted on it here and has a nice wrap up.

From The Canadian site The Globe and Mail

Most experts predict that routinely reading individual genomes will become a reality within five years as the technology to unravel the six billion chemical units that make up DNA gets faster and cheaper.

Kathy Siminovitch, director of genomic medicine at Toronto's Mount Sinai Hospital and the Samuel Lunenfeld Research Institute, noted that the first Human Genome Project rang in at roughly $1-billion (U.S). But with the new generation of "ultra-fast" DNA sequencing machines that have hit the market within the past two years, she said the bill is expected to drop to less than $100,000 by year's end.

The Sherpa Says: Coming soon 1000 USD genomes. Now who will read and interpret them? Even crazier....where is the evidence base behind treatment guidelines adjusted to your genome??? I can here the uneducated physicians now.But don't be scared my brethren internists. Stick with the Sherpa. We will find our way.

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........