Daniel Ballon Off Course with DTC testing!

I read an interesting article in the SF Chronicle today. It was entitled State off course on 'personal genomics' Authored by Dr. Daniel Ballon PhD...

He raises some interesting points that I would like to highlight.

Why would a state that regards itself as progressive and high-tech act to censor what we can know about ourselves? Though regulators may shut down unscrupulous firms, the services offered by Navigenics and 23andMe meet the highest standards of accuracy, validity and reliability. The laboratories employed by both companies are fully licensed and trusted by researchers around the world.

First off....it didn't start that way with 23andMe.....Also, I just found out they came to Yale Genetics in '06 looking to database people and their samples.......hmmmmm

California is progressive, but it is still a state which believes that government should help protect its citizenry, and this is likely why it acted. There were some really bad players out there....now that the well funded firms could hire legal defense to open back up, they have....those less funded buggers shut down.....who was more scrupulous.....I couldn't tell....but who was more funded I certainly could tell.......

I Highlight "the services offered by Navigenics and 23andMe meet the highest standards of accuracy, validity and reliability."

Simply because we need to ask what these three words are that Ballon PhD throws around as if they are the gold standards.....

Accuracy? Of what? Of what your genetic code is? If that is all they are providing, then maybe this is the most important thing...but if they start providing risk estimates....then that accuracy, I am afraid is terribly flawed and often not agreed upon by physicians or a host of scientists...So if we are judging that accuracy.....we have a big goose egg there....

Validity? Of what? A valid genotype? What is an invalid genotype (Well, that's what the natural born were called in Gattaca) Are the genotype results valid? I would say yes....the same as they are accurate.....in the genotyping realm this IS the same thing. But I think Ballon PhD is trying to get you to believe that the interpretation IS what's valid......For the majority of medical estimates (Which BTW IS medicine, I don't care what anyone says about that) their estimates are not valid.....validity used as an adjective describing assertions, arguments, conclusions, reasons, or intellectual processes that are persuasive because they are well founded. In this case that validity would be scientific or medical......most of these SNPs fail on both counts....therefore Dr Ballon.......DTC just laid another big fat goose egg.....strike 2!

A great example includes the fact that there are more failure of replications in SNP data, than replications......

Reliability? of what? The genotype? Isn't that the exact same thing here when we are dealing with As, Cs, Gs, and Ts? Are the letters what they say they are and can you trust that you will get the same letters every time? I hope so......But if you are talking about the reliability with which you can trust the interpretation reports.....once again I say you fail......why? The science isn't there to create a reliable report on most of these SNPs......So again.....Strike 3....

Don't believe me......look at the last month and the SNPs in 9p21 a region argued that is highly linked to heart attack.

1. linked to Irish heart disease

2. Failed to replicate in the Dutch

3. Replication in the Chinese

4. Now linked to Alzheimer's Disease if you believe it........

So which is correct? More importantly.....will testing this help us risk stratify any better? Will it help us treat any better? Will it help prevent disease? None of these questions have been answered scientifically yet.....Not a single one! No where is this mentioned in regards to validity, accuracy or reliability....yet these reports include risk assessments...based on these SNPs!!!!

He then makes this absolutely bogus argument....

If residents must obtain permission to see their own bodies, however, why can they look in the mirror without approval from a licensed cosmetologist?

Well, if I needed to put my eyes in a tube, ship them off to a lab, and the lab would need to tell me what I saw......I would say yes, that lab should be licensed.....

But, listen Mr. Biased, your statement tells me that your "Insight" is clearly skewed and biased

Unlike cosmetologists, doctors have a powerful lobby in Sacramento, and these technologies directly threaten their profits. Personal genomics aims to empower the individual, not line the pockets of an elite medical establishment.

So let me get this straight...

1. The doctors have more of a lobby than the billions of dollars in tech and in Google.

2. DTC testing doesn't line any one's pockets? Oh wait.....it lines the pockets of....oh wait, these companies are still bleeding cash......And BTW what doctor should you skip seeing because you have one of those new fangled scans....skipping doctors appointments is a bad thing.....that is one of the reasons why California stepped in.....b/c most patients are willing to trust an unvalidated SNP scan when it tells them they are healthy.....

3. These technologies threaten doctors profits?????? Have you ever seen a billing code for bogus SNP scan...insurance would never pay us to interpret this data......So no dipping into our paying patient populace......Sorry, another false argument....

Lastly, here's a myth buster for ya Mr Ballon....

You say

For example, it is currently impossible to know the hundreds or thousands of tiny genetic variations that help explain why someone loves roller coasters or horror movies. If 10,000 people join an online network for thrill seekers and start comparing their genetic profiles, the variations they share will be obvious.

10,000 patients wouldn't even come close to enough data to draw any meaningful conclusions regarding this highly variable phenotype of thrills.....SORRY......So stop making the public think it will.

So I ask all reporters.....if you are going to put this swill out there and hope it stands up as an argument......I say, think again.....

Daniel R. Ballon is a fellow in technology studies at the Pacific Research Institute in San Francisco. Contact us at insight@sfchronicle.com.

The Sherpa Says: Dr. Ballon needs to go to medical school or maybe just spend some time with the clinicians and scientists actually working on personalized medicine.....rather than hang with his Spit Happy crowd in the Silly Con Valley. Mr. Ballon, you stick to Cell Bio and I'll stick to Healthcare.......sound reasonable???? Sometimes business regulation is necessary, I think we see that crystal clear now.

You Know It's Bad

You know you are in for a grilling when the SACGHS says......"While we laud you for coming to participate in the conversation, part of that participation means that you may not like what you hear(More or less quoted from the webcast)"


Then in an "Interesting" Move.......

They ask "Would you be willing to sacrifice your bottom line to offer these services at say 100 USD?"

Wha???? This is such a crazy question.....This Assumes that the data they are presenting is valid, actionable and worthwhile....... All of which.....are debatable...AND that the public would want such services....

What am I talking about? I am talking about the opening of the 30 minute interrogation that was the end of the SACGHS meeting

They even asked the question "Do you have an IRB for all this 'research?'"

The response.................."We're workin on it"

Well, not really the end.....That was reserved for clean up hitter Kathy Hudson...(Whom, BTW I think is brilliant)

Her slide set covers some very key issues and the presentation did as well....

She even manages to quote Joseph Schumpeter, elegantly...

Schumpeter thought that the institution enabling the entrepreneur to purchase the resources needed to realize his or her vision was a well-developed capitalist financial system, including a whole range of institutions for granting credit.

This is very true, but what she quoted him on was this....

“process of industrial mutation that incessantly revolutionizes the economic structure from within, incessantly destroying the old one, incessantly creating a new one.

I.E. Let's destroy the Healthcare System via DTC Genetics.....Interesting....I wonder how the committee of healthcare players liked that slide? I wonder if anyone mentioned his other theory where advanced capitalism doesn't allow entrpreneurism to flourish because of regulations and the creation of a welfare state. Hmmmmm me thinks not...

When looking at the concerns, this slide explained them pretty well

Concerns About DTC Marketing
• Consumers can’t understand genetic information; it is complicated.
•Consumers vulnerable to exaggerated claims.
•Consumers may get tested without adequately considering consequences to themselves and family
•Consumers may forego standard treatments or make dietary or lifestyle changes without proven benefit
• Consumers may seek and receive unneeded and costly care

Companies may not adequately protect privacy of genetic information
•The tests that are offered may not be valid
• The laboratories that perform the tests may not be competent
• Test claims unsupported by evidence
• Inadequate protections for research participants
•No legal barrier to surreptitious testing of another

She Says the Options are

• Let the Buyer beware
• Demand transparency: information as
  the antidote
• Require third party review of accuracy
  and safety
• Take action against false claims
• Create a category of OTC LDTs
• Expand HIPAA
• Expand common rule
  

I personally think there are many more...And I am workin on that!

The Sherpa Says:

When speaking anonymously with a panelist they said...."It was surprisingly tame" When speaking anonymously with SACGHS attendees they said "This spells the end of unregulated DTC" So it sounds to me like the 2 sides may be engaged in a conversation where no one is listening to each other.......Or the may not be communicating effectively......

Sorry to Coriell, Stay of the New Jersey Turnpike

Sorry to the attendees at Coriell Yesterday. They were ready to start participating in the Delaware Personalized Medicine Project. I was scheduled to speak on the topic of "Patient Centered Genomic Medicine" Unfortunately, I was stuck on the Turnpike


Don't get in a car wreck in New Jersey. Trust me!

I don't know if anyone reads Medical News Today but it is filled with great information and studies. Today, it is reporting something which is of no surprise to me. From the article

A new report on genetic testing from HHS' Agency for Healthcare Research and Quality calls for the creation of improved public health surveillance databases and health information technologies to monitor the use of gene-based tests and their impact on patient outcomes.

For the government to spend on this testing, they want to know.......is it worth it? The problem with incorporating genomics into medicine is many fold. But the problem paying for these tests include a deep seated need for the government to know if what they are doing is cost effective. More importantly, is it leading to better outcomes. This type of study requires years and years of follow up. In addition, this type of study could be very, very expensive.

The report entitled:

Infrastructure to Monitor Utilization and Outcomes of Gene-based Applications: An Assessment, found current public health monitoring systems lack the capability to monitor the use or outcomes of gene-based tests and treatments. Report authors identified several limitations of existing databases and potential solutions to overcome these limitations.

So what makes a good test? What makes a worthwhile test? Time and study will tell. Until then we must rely on the professionals who have access to the current data. Ideally we would have a BBB of genetic testing. Or maybe just some continuing education.

Whichever Candidate you support it is likely that the government will support legislation, funding AND regulation.....Even If Al Gore is heavily invested in DTC genetic testing. Simply because the corporations may have ethics does not mean they are not exactly hippocratic.

The Sherpa Says: Yes it is true. Physicians not knowing about genetics could get them into malpractice. But running a DTC company could get you in trouble with the Fed....I guess an investor just has to pick their poison.....or their car crash

Osteoporosis and Gene Tests

Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures, especially of the hip, spine and wrist, although any bone can be affected.In simpler terms, osteoporosis is a condition in which the bones become weak and can break from a minor fall or, in serious cases, from a simple action such as a sneeze.

About 85-90% of adult bone mass is acquired by age 18 in girls and 20 in boys. Building strong bones during childhood and adolescence can help to preventosteoporosis later in life.

In the U.S. today, 10 million individuals are estimated to already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for osteoporosis.

In 2005, osteoporosis-related fractures were responsible for an estimated $19 billion in costs.By 2025, experts predict that these costs will rise to approximately $25.3 billion

So I ask you.....if we could prevent osteoporosis wouldn't we. Early detection and identification of at risk populations is key. Recently there were some great studies that came out of Lancet and the NEJM identifying patients which might be at risk. They are definitely associated in some sort of way, but not ready for prime time. Why? Because there are better predictors

Like?

Significant risk has been reported in people of all ethnic backgrounds.
Twenty percent of non-Hispanic Caucasian and Asian women aged 50 and older are estimated to have osteoporosis, and 52 percent are estimated to have low bone mass.

So more often in Asian and Caucasian women. What are other risk factors?

• Being female


• Older age


• Family history of osteoporosis or broken bones


• Being small and thin


• Certain race/ethnicities such as Caucasian, Asian, or Hispanic/Latino although African Americans are also at risk


• History of broken bones


• Low sex hormones


• Low estrogen levels in women, including menopause


• Missing periods (amenorrhea)


• Low levels of testosterone and estrogen in men


• Diet
  Low calcium intake
  Low vitamin D intake
  Excessive intake of protein, sodium and caffeine


• Inactive lifestyle


• Smoking


• Alcohol abuse


• Certain medications such as steroid medications, some anticonvulsants and others


• Certain diseases and conditions such as anorexia nervosa, asthma and others


• Loss of height (which may indicate a spinal fracture)

So what does genetic testing add to this? From the clinical side....Absolutely Nothing. The risk prediction from these above factors is much higher than the non-statistical significance genes in the New England Journal of Medicine. Nor the interesting findings in the Journal Lancet.

The Sherpa Says:

Listen, back to the basics before we hype up these SNPs in Lancet. Odds Ratios less than 2.0 are not very useful for clinical practice.....So why do they get all this hype???? Because "New Gene For X" Always makes headlines and sells papers.

Let's give everyone Beta Blockers in Heart Failure!

Ok,
So some people have been talking about this wonderful polymorphism in African Americans. This polymoprhism is in the GRK5 gene. What does it do? Well, before I look at any polymophism I always ask. "What does the gene do?" GRK5, short for G-coupled protein receptor kinase, this kinase acts as a switch that essentially turns off receptors. Such receptors bind catecholamines, which are sympathetic system neurotransmitters like epinephrine and norepineprhine. They also bind peptide hormones such as angiotensin, which is implicated in high blood pressure. For the lay person....this gene helps regulate response to adrenaline and other hormones that are in overdrive with stress and in this case heart failure (the inability of your heart to pump your blood).

Why is this polymoprhism important? For a long time there was a thought that Beta Blockers did not help African Americans in Heart Failure. I kept thinking "This is stupid. Not everyone of the same race is the same." More importantly the data with which we applied this broad racist thinking was not the BEST. This applies for many things in medicine. We often jump to conclusions when not thinking genomically. The age old debate about coffee is the same story as well. Until viewed in the light of genetics and CYP polymorphisms, one could say that a cup of joe is bad or good for you. It turns out, if you process caffeine poorly, big surprise.........you are at increased risk. If you metabolize fine....no big deal.

So how does this help us treat heart failure in African Americans? Here's the zinger from the author Gerald W. Dorn II, M.D....

“By mimicking the effect of beta blockers, the genetic variant makes it appear as if beta blockers aren’t effective in these patients,” he explains. “But although beta blockers have no additional benefit in heart failure patients with the variant, they are equally effective in Caucasian and African-American patients without the variant.”

Bingo!! Clinically applicability. But here's the kicker. Will testing for this be clinically feasible? Will the cost be feasible? Some are saying no...including the guy who I just quoted

"That doesn't mean African-Americans with heart failure need to be tested for the genetic variant to decide whether to take beta blockers," Dorn says. "Under the supervision of a cardiologist, beta blockers have very low risk but huge benefits, and I am comfortable prescribing them to any heart failure patients who do not have a specific contraindication to the drug."

What the hell? He just said that the risk benefit was well in favor of benefit for all heart failure patients. This 50 year old white guy(he graduated med school 27 years ago), just proved he was a 50 year old white guy operating under the old set of evidence based instructions. He just said "I am willing to spend the taxpayers' money on a medication even if it doesn't benefit the patient, because I think it would be too confusing to test the patient for this polymoprhism during the first 10 days of therapy"

But I am certain he doesn't see it that way. He sees it as, "I see 20-30 heart failure patients a day. Why? Because my operating expense has gone up and my insurance payments have gone down. So I don't have the time to test these patients....so I just spend the insurers money on these meds. Why? Because they work!" And that my friends is how everyone ends up overmedicated!

I wonder if he ever considered that the money saved and risk averted could be a nice way to reimburse him for the new model of healthcare this nation is now demanding? Hmmm.....Might be one way to get the 50 year old white men on board with Genomic Medicine......"Pay for appropriate usage or non-usage of medications" Listen, don't get me wrong. Beta blockade in heart failure is cost effective. But imagine how much more bang you would get for your buck if you could squeeze that much more effectiveness out of it.

We really need to know how this can affect care. This could be a great clinical example. Berci at Scienceroll is compiling a database of clinical examples. I think that as we see these cases add up, we will then begin to realize the power of Genomic Medicine.

The Sherpa Says:

The only constant is change, and times, they are a changing. I am blown away that this researcher didn't investigate whether it might be worthwhile to test these patients rather than let them be guinea pigs simply in the name of evidence based medicine. Genomic Medicine is here. The passage of GINA heralds its arrival. Even Burrill and Company believes it, so it must be true! To all my colleagues out there....Be Prepared.

Too good to miss

Ok....so I have been reading Hsien's discussions about DTC testing good or evil?

This spirited debate is very important. Everyone has concerns about regulations. It is the reason why 23andMe jumped the non-clia certified lab ship (And probably Why Andrew's results were delayed) But it is also why LabCorp has now locked out all other corporate genomic companies for now....

This debate is going to boil down simply to this...I posted yesterday and maintain this position

"Predisposition is Pre-Disease". This is the case with BRCA testing, it is the case with some robust SNPs. The ICD10 codes will catch up with this....

If it is not the case (i.e. for entertainment purposes only, NO HEALTH IMPLICATIONS) then they don't need medical regulation.

So I ask, are the SNPs which are being tested for and reported robust? Are they medically actionable? If so, then you are absolutely practicing medicine...You can't deny that at all..........

Once again from Dr Ralph Snyderman,

Today, most health-care expenditure is focused on the later stages of this process, long after the development of many underlying pathological changes. Until recently, it could be argued that the focus on treating disease was justified because the ability to predict, track, and prevent its onset was not technically feasible. This is no longer the case, and the emerging sciences of genomics, proteomics, metabolomics, medical technologies and informatics are revolutionizing the capability to predict events and enable intervention before damage occurs. Personalized risk prediction and strategic health-care planning will facilitate a new form of care, which we have called 'prospective health care' [1].

The Sherpa Says:
So is it really over-regulation? Or is it just calling some genomic tests "The Practice of Medicine". Which brings up an even more interesting point. Why would anyone want "health related genetic tests" if they Weren't diagnosing a Pre-Disease?

Genetic Over-regulation? Simple Answer.

Why all the worry over regulations?

I was washing the dishes this morning when it finally hit me. With all of this concern coming from Washington D.C. and all the entrepreneurs (like myself) pushing something to market for "brand recognition" i.e. the Mayo or Coca Cola....face it....there is a Branding Element. Well, while we are now moving through MBA or MD 101 what hit was the answer....

You may be asking yourself "What is the question?" But I am here to tell you that the question doesn't matter as much as the answer does. But if you must know....the question is "What is disease?" We have all these people talking about the wellness industry, but we have to be serious with ourselves. There are a whole lot of well people walking around with LDL's that are over 160 (BTW that is pretty high). But if they never get tested for LDL, they never have a diagnosis.

So, I ask you. "What is disease?"

From Webster's

1: obsolete : trouble

2: a condition of the living animal or plant body or of one of its parts that impairs normal functioning and is typically manifested by distinguishing signs and symptoms : sickness, malady

3: a harmful development (as in a social institution)

So what really is disease....Well to break it down it is "Dis" (Lack,Not, Away) "Ease" (Ease). So this basically says that anything which confers a lack/dearth of ease could be disease.

I think this definition is DEAD! The concept was created PRIOR to molecular diagnoses.

I read just about everything that Ralph Snyderman writes. Who is Ralph Snyderman? Ask Misha.

Seriously, he came out with an idea which I think is absolutely brilliant. It is called Prospective Healthcare. Not personalized, not genomic.....ProSpective. Why? Because we will be able to diagnose disease at earlier and earlier stages. His graph is even lifted and put in the WebMD/Navigenics CME course....which BTW is five pages and five questions. Not exactly a whole course line. So if you are looking for a "curriculum" Navigenics. Give me a call and I can help you out.

I have lifted a subset of his graph and put it as the pic for today.

I know, I know but I need to bring this full circle so bear with me ok?

Dr Snyderman has stated that

Today, most health-care expenditure is focused on the later stages of this process, long after the development of many underlying pathological changes. Until recently, it could be argued that the focus on treating disease was justified because the ability to predict, track, and prevent its onset was not technically feasible. This is no longer the case, and the emerging sciences of genomics, proteomics, metabolomics, medical technologies and informatics are revolutionizing the capability to predict events and enable intervention before damage occurs. Personalized risk prediction and strategic health-care planning will facilitate a new form of care, which we have called 'prospective health care' [1].

You gotta love it!

So he says tomato I say "Tomatoe". Either way you slice it. It is what it is. But here's what it means. "Is preclinical disease, disease? Can you diagnose it? Can you treat it?" The answer in some instances is unequivocally YES. This is the case for impaired glucose tolerance.....prehypertension....So I ask you "Can you treat BRCA carriers?" YES. Is it a disease? It has an ICD9 code(V84.01). And it does determine certain insurance coverage, such as breast MRIs.

Well....

Do you see where I am getting? Everyone is up in arms over Over-Regulation(get it?). I think the answer is simple. If your test indicates a predisease condition that "May occur", then you my friend are diagnosing the "New Disease" named predisease. Therefore, you are practicing medicine. So the litmus test and answer is this. If your test does what I have just stated, it should be subjected to the same regulations as the practice of medicine. If it does not, then it should be stated PLAINLY, not at the bottom of a report in teeny weeny writing. I.E. this test has nothing to do with you "Health"........

There...back to the dishes...

The Sherpa Says:

So is it really over-regulation? Or is it just calling some corporate genomic tests "The Practice of Medicine". Which brings up an even more interesting point. Why would anyone want "health related genetic tests" if they Weren't diagnosing a Pre-Disease?

Nice Quote Tom

I wrote several months ago about Tom Morgan and bogus MI testing,
I haven't talked about him in a while. But I remember when I was a medical student rotating in genetics at Yale. Tom was literally running around talking about how great SNPs were and how they hold the potential to help define heart disease risk. He was so animated that I quickly jumped on board as a resident. I pulled up Newsweek and guess what....Tom the super excited about SNPs and Genomic Medicine Doctor

From Newsweek ....But we already know where Newsweek stands on this.

Dr. Thomas Morgan, of the Washington University School of Medicine in St. Louis, worries that the business is getting ahead of the science. While researchers have clearly identified a chromosomal region linked to heart attack, for example, no single gene—including some being analyzed by DTC companies—stands out as the smoking gun. And undiscovered genes may turn out to be major risk factors. The result, says Morgan: "I might scare myself or reassure myself falsely based on the very limited knowledge that we have."

Wow!!! That's right. Tom is on the same page as the entirety of the field of genetics!
Does that mean this testing is worthless. Absolutely not....when viewed in the light of an appropriate medical and family history.

Also today I want to highlight how quick information in this field travels. I was recent speaking with a member of CorbettAccel and we chatted about marketing and communication. I told them that guerrilla works best....believe it or not. Speaking of Guerrilla........
You should check out news.thinkgene.com Berci spoke about them earlier last week and I wanted to let you know they are out of beta. Good Luck Guys.....this field moves at light speed. BTW you should check out the founder's blog as well.

The Sherpa Says: "Market Share doesn't wait for the evidence"....which is precisely why we set up shop in 2007! I hope other brick and mortar personalized medicine practices jump up soon. I look forward to helping them with the nuances of growing a practice while delivering the best care available. As the say....imitation is the highest form of compliment.

Paduan Learners and Francis

What I always find amazing is the enthusiasm with which medical students learn genetics. My colleague came back from some of our house visits and I had some time to teach. It is as if they were never taught genetics to begin with. I just finished up an hour long lecture with the 3rd year medical students of New York Medical College. I often hear so many..."Oh Yeahs" or "Oh....I get it" answers....That is what motivates me.

After the hour long lecture....I often the tell them that they now know more genetics than their attendings (Older Physicians). This often makes them feel very empowered. I walk these students through the history of modern medical genetics and tell them about the lack of providers in the field. Often this is accompanied with several expletives about how Mendel did us wrong.....


Did you know that medical students in this new century still think that 1 gene makes 1 protein makes one phenotype? It is true....despite the evidence for alternative splicing, methylation, epigenetics...I could go on and on. There is a reason why a certain unnamed CEO at a certain unnamed genomics company said "Teaching Doctors genetics isn't hard....It's impossible"


I think you know who that company was........Unlike others that are teaching physicians through CMEs.


What I really want to know is.....how many doctors are doing what I just did? I am looking to build a Clone Army and don't have the ability to go to Kamino. So to quote Jerry....."Who's coming with me?" Please email me!


The Sherpa Says:


Congratulations to Francis Collins on his recent Ethics award. He is the George Washington of our genomic union. If we could only clone thee....methylation and all!

Over-regulation

Today I wanted to focus some attention on the issues of regulation and over-regulation. This is super important now that Wired has called this "business" an Industry. (Mr Goetz, next time feel free to call me when looking for quips.) When writing any good business plan one should obviously do a risk analysis and a SWOT analysis. If this is not done there likely will be failure to identify perceived threats to your business or business model.

Why is the Sherpa talking about business? Because, Genomic Medicine is being driven by business. Why? Because academia has failed to take the bull by the horns. Why? They are comfortable in their own realm. This is a stretch for them. I often like to blame this on the fact that Geneticists aren't usually trained in Internal Medicine (Most are Pediatricians) and Internists aren't trained at all in Genetics. While this is true, there are many other physician stake holders out there including OBs, Surgeons, Oncologists (Which are usually Internists), FPs, RNs, DOs, I could go on and on. But the mere fact that I don't mention much about them is simply because it is more of the same. In addition, only recently has the government been putting its dollar behind genetic research in common diseases. So why touch this risky topic of Pharmacogenomics, Risk Stratification and Genomic Medicine?

If you look at the business side of Genomic Medicine it becomes clear it was designed by those who do not value genetic services....other than testing. But here's the real reason: Genetic Care is a losing proposition. You cannot make millions of dollars from hiring the best genetic counselors and geneticists and taking Insurance payments. In fact you would be lucky to get minimum hourly wage for their services. Don't believe me? Talk to the Advisory Board Company.

So why is it a push, push, push for testing? Because insurers pay for testing...in fact they pay a pretty penny. Myriad charges 3125 for the BRCA analysis, some DTC companies charge several hundred more for "brokering" the test. They claim that the rest is cost for genetic counseling. If this is true, I applaud them for paying the genetic counselor 300 to 400 per case. That is the proper salary for them. If not, then where is that money going?????

To bring it full circle......Testing is where the money is at (right now). What is the Threat to testing? Over-regulation. The government can make it so tough to operate a lab that it is not economically feasible. Will that ever happen? I sure hope not....but it is headed in that direction. This is why the big firms like 23andMe are now scrambling to switch to CLIA approved labs.

Ladies and Gentleman, I submit to you that CLIA is only the beginning.......

I know that I have been pushing for self-restraint from these companies. Media hype and Marketing Ploys even affect physicians. This is the reason why they could kill this field for all of us if not done properly. Don't get me wrong, in the seeds of these companies lies some potential to do great things....It just hasn't been growing that way yet. But if you piss off the AMA, ACP, SACGHS, FDA, CMS, GAO, US Senate, Department of HHS, FTC, ACMG, NHGRI....I could go on and on.....Point is, the beltway is salivating over this topic.

But the truth is, by rushing to market they have brought this plague of over-regulation on all houses. This is coming, trust me. Government always has a way of stepping in too late and then over reacting (at least when it comes to legislation). This was the threat that should have been anticipated.....but more importantly...In any good business plan there should be some strategy to mitigate this threat. Where in the hell was that? Why hasn't this been enacted? Rookie mistake.

The Sherpa Says: We need to work with the government. Now more than ever. Otherwise....the US Govt. could crush the entire promise of Consumer Invested Health Care. Or at least destroy the vendors who stand poised to bring about this revolution. Look no further than at our candidates

4 Days too long

As I sit here in the Sheraton New Orleans before our presentation I am re-living my days here in New Orleans....

When we arrived I immediately had to go get Jambalaya.....and then diarrhea..........

The next day I went to the "World Famous" Cafe DuMonde....I was filled with excitement about this exotic sounding place.....If I only would have google'd it first. When I approached the cafe from Jackson Square I saw what seemed to be perhaps a beach side cafe with a starving artist out in front of it.....I must admit when I got in the Green and White Awning open air cafe I saw a neat business model and tasted what I deem "smooshed funnel cake". It turns out at the Cafe Du Monde, the waiters take your order, pay the cashier...almost as if they are reselling the goods........meaning the Beignet! That fried dough smashed with powdered sugar....sounding eeerily like a Rye Playland funnel cake. Guess what in addition to the funnel cake....sorry "Beignet" they also sold coffee laced with a retinal poison called Chicory. That's correct...long term consumption of this substance leads to dimming of the vision and damage to the retina.

What in the hell? Clog your arteries and go blind at the Cafe Du Monde......So good actually that I went twice! Take That Medicare! Feel free to pay for my stents!

The Sherpa Says:

Stay Tuned for more...I have to go set up now.

500 Hospitals want to know....

Lots of stuff happening online today. I just left a conference call where I was the invited guest panelist along with Robert Resta CGC. The Advisory Board Company and The Innovations Center presented an Issue Brief entitled-The Genetic Testing Frontier: Impact on Clinical Care, Market Opportunities. Hundreds of hospitals were online wondering how they too can get a piece of the action.....

Also....did anyone read the Washington Post today? Genetic Testing Gets Personal again another article on this "revolution" non subscription link here

"We call it consumer-enabled research," said Linda Avey, co-founder of 23andMe, based in Mountain View, Calif. "It's about changing the paradigm of how research is done."

Well Said.......You could also call it uninformed cohort analysis...."Free Kits?" Come-On....nothing is free. Davos, you sold your DNA for some fancy flash animation and trinkets....I am guessing the Belmont Report is not required reading in MBA schools...Hey guys don't worry, here are the Cliff Notes

The Belmont Report explains the unifying ethical principles that form the basis for the National Commission’s topic-specific reports and the regulations that incorporate its recommendations.

The three fundamental ethical principles for using any human subjects for research are:

(1) respect for persons: protecting the autonomy of all people and treating them with courtesy and respect and allowing for informed consent;

(2) beneficence: maximizing benefits for the research project while minimizing risks to the research subjects; and

(3) justice: ensuring reasonable, non-exploitative, and well-considered procedures are administered fairly (the fair distribution of costs and benefits.)

These principles remain the basis for the HHS human subject protection regulations.

Paradigm of how research is done???? Isn't that why we developed IRBs? To protect from those who want to change the paradigm and injure the patients? IMHO these companies need to immediately develop research protocols and IRBs. End of story....nothing less. The consumer should be allowed to at least ask questions to another person.

It can be entertaining, Venter said, to learn one has a gene for soggy earwax. "But if you're on the receiving end of one of these tests and are told your probability of having a serious problem is 62 percent, what the hell does that mean?"

And that is assuming the results are correct. As it turns out, many gene tests today search for DNA patterns that have been linked to a disease or trait in only one or two studies. Such findings are often overturned by later research.

Enter the trained professional.....This is precisely why we need more Sherpas!!!

Dr Venter is completely correct....the brick and mortar where professionals exist is the transition point. Even 500 hospitals online today acknowledged that. Now where do we get these individuals?

Exacerbating the problem is that virtually no one is watching over the industry. The Food and Drug Administration does not regulate most gene-based tests, and there is no federal proficiency-testing system for companies offering them.

Enter the SACGHS and EGAPP...2 organizations devoted to helping best practices....In addition, the ICOB at the Delaware Valley Personalize Medicine Project will also help shape this future.

"It creates an air of charlatanism that doesn't help the field," Venter said.
All told, concluded a study in this month's issue of the American Journal of Human Genetics, "There is insufficient scientific evidence to conclude that genomic profiles are useful in measuring genetic risk for common diseases or in developing personalized diet and lifestyle recommendations for disease prevention."

That is my number one concern. Here's why...geneticists and genetic counselors require referrals from physicians who don't speak genetics, but watch the national news and read the New York Times...If they link Medical Geneticists with Scientific Match.....There Ain't no way in hell any self-respecting, butt-covering, good physician will refer patients to such "Qwacks" simply due because of the confusion. All press is good press? Don't think so...especially when the NEJM posts such a confusing article failing to clarify the difference.

"I very much worry that all this emphasis on a 'gene for this' and 'gene for that' raises the risk that people will conclude that that's the whole story," Collins said. Instead of empowering people to make healthful changes in their lives, that could simply make them "more fatalistic," he said, "in which case, what's the point?"

Me too Francis...Me Too....

The Sherpa Says:

To climb the mountain we need unreasonable people that won't quit....Corporate and Academic can exist together...provided they do the right thing. Do it yourself surgery is probably just as "Revolutionary" so why isn't anyone on that money train? BTW the pic is of do it yourself LASIK.....I bet that is a best seller.

They're HEEEERE!!! Navigenics in New York

Well in a move to trump NY or a business plan that does include physicians. Navigenics will Launch April 8th in NYC!!!

That's right

From a counselor's email sent by dnanyc@navigenics.com

Dear xxx,

Navigenics invites you to be one of the first people in NYC to experience first-hand a leading-edge approach to health and wellness.

Navigenics is launching its first genetics service April 8th. We truly believe this company will revolutionize the way we think about our health. Our first service, called the Navigenics Health Compass, tests for genetic risk markers for 18 actionable common conditions—cardiac disease, several cancers, Alzheimer’s among them—and arms you with specific information on how you can mitigate your individual risk for developing each condition, including personal genetic counseling sessions and customized health and wellness content. To celebrate the launch of our first service, we are coming to New York City for two weeks in April (April 8 – 17) to host a series of exciting and informative events. We will be installed at a SOHO location, and I encourage you to join us for some of our events. (Please see the calendar invitation below.)

Please help us celebrate this transformation for medicine: from a “sick care” model of “wait and see” to the emergence of early risk detection. The time has come to empower individuals with the opportunity and knowledge to take preventative steps, and a hands-on approach to their family’s health and wellness!

All the best,
The Navigenics Team

RSVP@navigenics.com

Now it will be interesting to see how their competitors 23andMe and deCodeMe react. Our practices stand ready to pick up the pieces and serve as an information source for both patients and physicians who have lost their compass, or just want to learn about this new technology.

The Sherpa Says:
I'll be there. How about you? To all my physician freinds, give me a call and I can explain what the hell is going on.... You should go to these events....Seriously, they look pretty impressive

A thought....

What if we had a 1000 USD genome by next year? Where would we be? What would we have? What problems would that create? Who would benefit? Who would lose?

I have been thinking alot about this lately. Mainly because I had known for a while that the Applied Biosystems' Product was coming in under 60k. Trust me....under 60k USD. My friend and ex-President of TV Guide had sent me something this week and I wondered how quick this would move up the charts and into the press.

So I ask my readers..."Where would we be in 1 year from this date if we had the capability to sequence a whole genome for 1000 USD? No not the SNP scans being paraded on the Today show...A whole genome, CNVs and all. What problems would that create? Who would lose? Who would benefit?

I have some ideas and will post them in the coming weeks....Starting with "Where would we be?"

The Sherpa Says:

Let me know what you think....

I am so getting sued by ABC!!! Or NBC take your pick!

Maybe not 99% similar. Suracell? Not so Sure

Today I want to post on several things that you may have been reading about. The first of these is the twin studies on copy number variation and methylation. Huh? I said "copy Number Variation and Methylation" What are these? I thought everything was about SNPs? I am certain you must be asking yourself these questions. Well, fear not. Unfortunately methylation and copy number variation do not have millions of dollars, corporate giants, VC or PR firms pushing their importance....

But these unique changes make us probably on the lines on 90% similarity. Which, when you look at each other makes a little bit more sense. Right? Just like the fact that 18k genes encode our complex organism. How in the heck does that happen? Well I am here to tell you that SNPs are just the first chapters of our genome novel. Which is a great thing...Imagine if we said...."That's it, end of the story...we know it all" I think that day would be a very sad day for all of us....because on that day G_d would certainly play a joke on all of us. This reminds me when my friend said "You know, I've got it all figured out." The next day, he wrecked his car and then found out he was going to be a daddy.....Well, I guess everything that was in his previous reality was figured out...

So what is the deal with the twin studies? Identical twins are supposed to be identical right? Incorrect. Huh? Well these things have been shown in other studies as well. Let's face it, as geneticists we know that even identical twins are not so identical. In the 1980s and 1990s there were multiple reports of things like Non-random X inactivation leading to X-linked diseases in females. Yet we were still teaching mendelian genetics in university and not teaching any genetics in medical schools.

We don't have it all figured out...and the stuff we have figured out is probably not ALL figured out. A recent article in the American Journal of Human Genetics reminds us that we need to take everything in perspective and always double check things....especially when it comes to your health. They review the science behind Suracell and Salugen and Sciona.....But they do it with a sneaky name A Critical Appraisal of the Scientific Basis of Commercial Genomic Profiles Used to Assess Health Risks and Personalize Health Interventions

That certainly sounds like they reviewed 23andMe and deCodeMe doesn't it? Well....they did not. However they do comment that the SNPs used in the "Nutrigenomic" companies...which were already given the "Honorable Mention" by the GAO. What is the take home on Nutrigenomics?....Find the right company and understand that our understanding as physicians and scientists is pretty young....We have only gotten through the first chapters...

The Sherpa Says: Let's keep reading this book of life....Act when we can but not in an irrational manner. Let's rely on the science....and let the Sherpas guide us...not the press or a rock solid public relations firm. Last but not least, we may be able to sequence a genome for 60k....but we still have a HUGE knowledge and Manpower Gap!

60 is the trigger for Alzheimers

Finally, a weekday post! I know, I have gotten in this vicious cycle of posting on the weekends and keeping them up for the first few days of the week, just so those readers who don't check the rss or even switch on a CPU on the weekends don't miss a beat. Listen, I read Tim Ferriss' book too...but I now have to step it up.....

Today I want to bring an interesting topic to light. Why are people scared of genetic testing? Is it the discrimination (which doesn't exist) or is it something more deeply rooted like "Genetic Determinism"? In counseling for things like breast cancer risk, some often say..."You may have outlived your risk for early onset breast cancer" This is a sticking point for me.....Who ever outlives genetic risk? Completely, I mean. There are so many variables out there that can give you cancer...who is to say that just because you are 65 your BRCA mutation won't give you that cancer? I couldn't be hard pressed to say that so vociferously. I say this because even with the strongest genetic influences there is always an exception. This is exactly the case with Alzheimers and ApoE4.

Well now a study recently released called the Arizona ApoE4 Cohort Longitudinal Study of Cognitively Normal Individuals (Say that 3 times fast) indicates that 60 may be the age of kickoff for cognitive decline in ApoE4 carriers.

According to the article in Internal Medicine News......
There is a particular pattern of decline in ApoE4 homozygotes (2 copies) that tend to precede any diagnosis of mild cognitive impairment (a stage prior to full blown alzheimers or other dementia). Or prior to anything that can be seen on radiologic brain imaging....

So what does this mean for the clinician? It is huge....Instead of outliving your risk...we now may identify those with ApoE4 who will likely get Alzheimers......CAUTION, these results are currently being replicated and I wouldn't want to promise anyone that we have a perfect ApoE4 phenotype detector quite yet. But it is important to have this....Why? Because up to 10-40% of homozygotes will NEVER develop Alzheimers. So when can we say you have "Outlived your risk"? The answer is never...but we can say "You will be less likely to have ApoE4 related Alzheimers than someone who is your same age with this cognitive deficit." That is what should be said.

Now the real quandary..."How can we stop it from getting worse doc?" That is for another post.

The Sherpa Says:
Too many in the genetics field are quick to give medical advice. I warn that perhaps we should check our training and liability insurance before we start doing this. I recommend that all of us in this field work together to provide the best care possible. I never say never and never say always....in genetics as in life, there are NEVER any definitive answers...except "sometimes" and "it depends" That being said..........We should always be performing routine screening exams on carriers of any genetic changes. Confused yet? Don't be. Just follow my lead.

CF "success" story

Today I am writing about something I call truly Personalized Medicine. This topic hits near and dear to my heart and I am going to talk about this because it is an ethical dilemma.

The recommendations for genetic screening by the American College of Medical Genetics, the American College of Obstetricians and Gynecologists, and the National Institutes of Health were issued in 2001. According to recent letter in the NEJM it turns out that the birth rate of children with Cystic Fibrosis has dropped.

The number of infants born with cystic fibrosis in Massachusetts decreased by 50% from one four-year period to the next according to this letter in the NEJM. They attribute this to the Newborn screening available in Massachusetts since 1999. In addition they also report a drop in those patients born with "supposedly" the worst outcomes...those with two Delta F508 mutations. This is the most common mutation and has been "associated" with worse outcomes. But not all rests on this gene, there are modifiers of this disease.

Here is the most important point they make.....The children born with CF in the future may actually have less significant disease and may need to have less aggressive or less early interventions.

But here's what they don't say.....Preconception screening for this disease is important, but a highly personal choice..... despite what the ACMG and ACOG say. There are some children who are doing just fine with CF. As for adults with CF like the 74 year old patient who I diagnosed a few years ago, I am certain they would not want to have never been born. Especially my friend who now has CF AND 2 very healthy children. He would want us to be able to predict worse outcomes preconceptionally. We are on that road now. But until then we still will be doing Preconception evaluations as well as Prenatal evaluations. This is because the aforementioned patients are the exception and not the rule.....

Genetic Issues are complicated. Despite this seemingly great report, there is more to this story....Much More. This is why I have had issue with haphazardly Shipping off CF testing for prenatal care and the poor guidance give by some OB's/Midwives regarding test results. This is not to say all OB's do a poor job of giving pre and post test counseling....but the data indicate that quite a few do. Only 19% self-reported thoroughly reading ACOG's Guidelines on CF testing!!!! Only 1 in 5 OB/Gyns can answer 5 fairly simple questions regarding CF correctly...at least in some groups of this study. This indicates a knowledge gap. I have seen it personally and it is quite distressing.

The Sherpa Says:
To get the best evaluations, you need people trained in the field, skilled with this complicated type of testing AND its complications. This is why I ask that every Ob sending genetic testing at least calls a geneticist or genetic counselor. We cannot assume that everyone knows what we know! If you are a pregnant or planning please ask your OB to let you speak with a geneticist if she sends genetic tests.....