Thursday, November 27, 2008

The Health Thing to Do This Thanksgiving

In the US, today is Thanksgiving. A day where family and friends come together and appreciate what we have. We consume massive amounts of food, drink, some smoke, and not surprisingly get admitted to the hospital the next day.

This year I would like to offer up the one healthy thing you can do. Take your Family History. Started in 2005, the Surgeon General has named today, National Family History Day. So visit the HHS website and find out who has what, who died, how may end up saving your life. When your done and if you are concerned about it, Come See Us! We even do home visits!

The Sherpa Says: Happy Thanksgiving to all. Today I am thankful for YOU, my readers. Have a great Holiday!

Wednesday, November 26, 2008 debuts!

I love the web. I have a twitter that is only shared by some good friends....but it never fails that I have people who are interested in what Helix Health of Connecticut is up to "lurking" my twitters......(I always wondered, are the people who use twitter called Twitterers or just Twits?)

This is the case with a company. I was informed today that someone at was now following me.. So I went to their site... It was a face page that I have up here....I began to wonder who was following me on twitter, so I dug deeper....

It turns out that was founded by PhD Geneticists, not MD Geneticists and is run by the a company called discoverme technologies.
What is MyGeneticist and who are DiscoverMe Technologies???
From their site
"At the heart of DiscoverMe Technologies is the mission to help people live healthier, more peaceful lives by facilitating informed medical decisions based on our analysis of personal genetic information."

We are committed to high standards of integrity in contributing to the best interests of our clients, health care professionals, our team and our communities, based on our continual pursuit of scientific, clinical and operational excellence."

"Founded and operated by scientists, DiscoverMe serves to complement existing healthcare systems and to make a positive impact on society by facilitating informed health choices."
So I then began to wonder....What is
myGeneticist is a service that enables individuals to understand the information stored in their DNA, so this knowledge can be used to make healthy life choices.
myGeneticist offers continuously evolving service suites based on scientific advances in pharmacogenomics, where drug prescriptions and dosages are matched to complement an individual's genetic makeup.

Through myGeneticist, clients will gain access to the most comprehensive genetic analysis of their DNA and, with the help of our highly accredited clinical team, be able to understand their most appropriate drug choices and dosages for any given situation, where quality scientific research enables definitive clinical action.

Conversely, our clinical team will work with partnering healthcare providers to facilitate the use of our services to augment existing healthcare clinics and practices.

Lots of words, but still no answers...Who is i.e. the clinicians and scientists? and most importantly what do they do? A highly accredited clinical team, sounds alot like MD geneticists or maybe clinical pharmacologists or maybe just MDs. I wonder who?

The Sherpa Says: A lurking twitterer reveals a stealth service which looks like it will launch in the PgX space, very, very soon......I look forward to finding out who they are and what they offer....We need more telegenetics services, especially when it comes to PgX.....

Tuesday, November 25, 2008

Death of the MicroArray/oaCGH

I just got out of a lecture given by Allen Bale M.D. a researcher and clinician here in the Department of Genetics at Yale....

I have come to the conclusion......

MicroArrays are going bye-bye....

Why? Allen detailed several unique strategies to "Trick" High Throughput(HT) Genome scanners into doing the heavy lifting, or what used to be heavy lifting/expensive lifting of microarray analysis.

How will this beat MicroArrays?

1. No more expression Arrays....Instead you can do reverse transcription and then do HT sequencing.....bp length too small? Just link all the sequence together.....

2. No more cytogenetics and Array CGH. Solexa's machine can churn through these sequences pretty quickly....hell, if nanopore comes through we could technically assess methylation at the SAME time!!!

3. It will beat them on price. When you have hungry lab rats trying to use their governmental grants as cost effectively as possible, they will find a way to "Adapt" their research to using these machines.

Bottom line.....places like Yale are already beating the "business" of MicroArray technology. That's why Illumina bought Solexa....they already see it coming..

The Sherpa Says: If I were an investor, I would steer clear of companies that are ONLY in the MicroArray business.......And if you are in the diagnostic space......beware of SMS, it will completely replace standard diagnostic tests...... Why do a BRCA sequence when you can just look at the mutations in a SMS run???? For 6000 Myriad will do all the HNPCC costs 12 USD to run them through a do the math......and the DTC genomics companies are already lining up with NextGen......

Sunday, November 23, 2008

Paradigm Shifts.....

I am busily preparing for the Coriell ICOB meeting in Philadelphia coming up shortly. We are set to examine a whole host of new SNPs and their relevance to disease. I also am ramping up our practices in Connecticut and New York City. Traditionally a consult service, Helix Health of Connecticut is going to really put its money where its mouth is...we are taking on a full time role in management of patients.

We certainly are excited about this move. We initially didn't want physicians in our communities to think we would want to "steal" their patients....which has never been our aim....but now after multiple requests by our consulted patients we will begin seeing full time primary care patients in our clinics starting in January of 2009.
Call now to start an intake, we are already filling up quickly.....

We will carry out the usual intakes and genomic consultations, but this time we will also be doing the full time quarterbacking. Sniffles, Chest Pain and Depression all deserve Personalized Medicine, don't you think?

Our team is committed to this and stand ready to serve.

We will be carrying out some amazing projects which I will share with you shortly.

We believe our communities are ready for this care, we hope the government catches on before it's too late......

To Your Health,


Thursday, November 20, 2008

Oprah's Community against 23andMe

When Public Relations Backfires

Genes provide Minimal Benefit!!!! Seriously Oprah!

Genotype Score in Addition to Common Risk Factors for Prediction of Type 2 Diabetes......

That's right, the New England Journal of Medicine has 2 publications in the Journal this week. What's the take away?

Paper One: Conclusions A genotype score based on 18 risk alleles predicted new cases of diabetes in the community but provided only a slightly better prediction of risk than knowledge of common risk factors alone. The C-statistic was 0.900 versus 0.901......some on....can we even call that better? The nearer the C statistic to 1, the better the predictive value of the can we really say it is worth it???

Paper Two: Conclusions As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up. In this study they use the area under the ROC, where the change is 0.74 to 0.75....again lackluster results...

You tell me? I just gave a lecture to several residents in Internal Medicine......I asked what the barriers where to taking a family history. One pragmatic resident said "So let's say I get the family history. What will I do clinically different?"

These articles in the New England Journal of Medicine make me pose the same question.......

What do I do with this only slightly, increased ability to pick up disease risk?

The answer? No one knows......Is it worth spending thousands of dollars on a test that doesn't dramatically improve detection of predisease risk?

I am not so sure.....

The bigger question is, are predisposition SNPs what we should be studying instead of rare copy number variants????

The Sherpa Says: With stats like this, DTC companies will be dead and so will the microarray business.....Will we achieve personalized medicine with such disappointing results???? Yes, but not via DTC...or via Oprah.

Tuesday, November 18, 2008

Not Intended to Diagnose or Treat

Andrew at ThinkGene comments on something that I have not been able to effectively explain.

We trust health assets like “medical advice” to exist. That is, we trust that public medical information describes reality such that it may be applied to measurably improve health. This is a challenge because medical advice, especially preventative medical advice like genomics, is a trust asset: an abstract idea with value applied to the indefinite future.

This is a very precise explanation. We pay for medical advice.......which may include diagnosis or treatment.......We trust trained health professionals to give that advice. We trust that they are capable of giving that advice......Why?

Well, we have a licensing system in this country that helps us assure that quality. In addition to that licensing we have things such as Board Certification or eligibility which also let us know that the practitioner has a certain set of skills, verified by a specialty.

These hurdles are required. Why? They are required to help establish "trust" in the system...

Andrew goes on to say

However, that trust is under attack, and as the immediately profitable but eventually catastrophic erosion of the term “insurance” now jeopardizes the financial industry, the meaning of term “medical advice” is now being eroded by greedy companies.

This system had been under attack for a very long time.....It had appeared that things such as "Alternative Healthcare" or "Nutriceuticals" had carved their own niche and it was Understood by the lay public that this system existed "Outside of the trusted practice of medicine" Thus the DIETARY SUPPLEMENT HEALTH AND EDUCATION ACT OF 1994 opening the field wide open for alternative care.....Prior to this the FDA regulated nutritional supplements.

The public knew that these systems existed in parallel tracks and that the quality of care by alternative systems would likely need to be "backed up" by standard medical care....a very small few, swore off western medicine, but these were the patients who would often present to an Emergency room with some "Morning Report" type case of undiagnosed diabetes, heart disease or cancer. Morning Report cases are often tales of very bad diagnoses (Bad for the patient, incredibly instructive for the resident)

But what is happening now is the replacement and possible erosion of the trust in medical advice. Why? Science or perhaps PseudoScience has evolved. Reporters relying on press release have adopted "Newly Published Results in Nature Science" as the Truth......Despite this not always being the case....even Russ Altman commented on this the other day.

The public is now understanding that Genomics is part of healthcare.....and with good reason, it IS healthcare. But the layperson doesn't have such a nuanced view and can't understand limitations of Non-Medical Medical Advice when it comes to genomics.

I Repeat "But the layperson doesn't have such a nuanced view and can't understand limitations of Non-Medical Medical Advice when it comes to genomics."

A gene is a gene, and to convince them of otherwise takes quite a bit of effort. The string of though goes something like this: "Genes are medicine, thus a genetic test is medicine.....and genetic advice, must be medical advice....

Thus, I implicitly trust the genomic testing advice....which in disclaimer is not for "Diagnosis or Treatment"

Andrew has reported on precisely this confusing thing on a DTC genomic website and press release. It can be easily viewed as confusing when a company tells you "Helps the patient make informed personal health decisions" Despite Andrew highlighting the "state of the art medical advice and services" he should have high lit "Helps the patient make informed personal health decisions"

This is the crux of this argument. When a patient usually wants advice about personal health where do they normally go?

The Doctor....Despite WebMD being the first link for Medical Advice on google, we eventually end up at the doctor's office...BTW the web tools for genetics in medicine are woeful, with over 1/3 having wrong answers or misinformation...

So what is personal health? In my opinion it is the realm of medicine. Health can be viewed in many ways, but protecting health and restoring health has always been viewed as a medical trait. Ever heard of preventative medicine?????

So Andrew is correct, the line is getting awfully blurry. When companies start making claims which blur that line while hiding under the legal nomenclature "This Service is not intended to Diagnose or Treat" it can be very confusing for the public....and with fantastic PR and being named as the invention of the year, we can be certain that the public is starting to lose sight of that line.....

But I say, isn't this what these companies want anyways? They want to replace modern care with "Wiki-Style" care.....I think we have seen that already...

This may or may not be a good thing.....Personally I think it is a horrible thing, but the scientist in me accepts the null hypothesis "There is no relationship"

So when would it be a bad thing? If the replacement of current medical advice takes place without the same licensing and regulatory guidelines that exist in current medical advice, then we may see a true erosion of trust in Medical Advice, which when it happens will lead us right back to where we began, with skilled professionals giving us the trusted advice we sought in the first place....

The Sherpa Says: "Genetic/Medicinal Advice" could be placed back in the dark ages if we start allowing it to be sold without the stringent regulations or to be able to jump the turnstyle through legal jargon and avoid regulations that are placed on it currently. This is one of those dangerous shortcuts that the Sherpa won't jump start the system by cutting the climbers off at the knees simply because you don't have enough crampons to climb the mountain....

Monday, November 17, 2008

Francis Agrees with the Kid!

First, Hat Tip to Mr Weber, a longtime reader of my blog. Thanks to him for bringing this to my attention.

Well, I also said that the slack could be filled by Physician's Assistants and Nurse Practitioners. Which probably only fired up the NSGC more.....

It turns out someone......Francis Collins agrees with me.

Collins and the other speakers noted the emphasis in PA training on patient education and taking family histories and PAs' ability to spend the time with patients needed to obtain a detailed family history.

"The current system puts physicians in a difficult position," Collins said. "There's too much emphasis on procedures, and not enough on personal interaction. Therefore, the heavy lifting will have to be done by PAs and nurse practitioners." He described the PA profession as a possible "fulcrum" for the integration of genomics into health care.

So Mike, if you read this....give me a call. Sorry I missed yours......

The Sherpa Says: We need PAs and NPs to do the heavy lifting in obtaining family histories and helping to carry out genomic medicine. Why? Most CGCs wouldn't get that a poor reaction to wellbutrin could be due to a cytochrome p450 2D6 polymorpism. Or that a Reynold's Risk score is altered when identifying family members with heart attacks.....They could learn, but it would likely take another 2 years of training an already overburdened field......

Friday, November 14, 2008

When family history falls short v.1 and the Wall Street Journal

When does family history fall short?

I outlined it in my last post but I figure now might be a good time to review one of the instances when family history falls short.....

But first I want to clarify. When I say family history, I mean at least a 3 generation examination performed by a trained healthcare professional.......not a meeting over Thanksgiving Dinner.....

Those four scenarios I mention include

1. Rare chromosomal anomalies that occur in less that 1% of the population
2. Rare monogenic disease
3. Congenital Anomalies
4. Severe Trauma

Today let's focus on Rare Monogenic Disease. Why? In the Wall Street Journal today, there is an article about a man who is stricken with EOAD.....Early Onset Alzheimer's Disease.....

From the article

"Now 51 years old, Mr. Kammerer, like many Alzheimer's patients, had no history of the disease in his family."

This is a common thing I hear about Alzheimer and yes, even early onset Alzheimer Disease....

Why is this important? Well, we have very little in the way of prevention for AD, we have pretty poor therapies as well. So naturally we would like to know what's coming, and avoid or at least plan for the train wreck....

When I was speaking at the American Geriatric Society meeting in CT earlier this year, I went over APOE e4 testing and Early Onset Alzheimer Disease too.....we covered in some broad strokes, but also cleared up a lot of misconception by physicians...

Yes....but first some good Stats:

1. Family History of AD increases risk of AD lifetime by if you have a baseline pop risk of 7-10% this would be 25-50% lifetime risk....

2. Genetic testing identifies 40-80% of EOAD, depending on the study you read

4. 60% of those who have EOAD have a family history.....meaning FamHx misses 40%

But for this important caveat......

Although most individuals diagnosed with EOAD have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, or reduced penetrance.

So do you guys understand why I say a family history should be done by a trained pro? You can miss things like this, especially if you don't ask about ages of death or other causes......

I ask if anyone has died in a car crash when I take family histories.....not many people do that....but it can be a predictor of seizure disorder, sudden cardiac death, Alzheimer disease, have to know what to look for......

So what I found most interesting about this story.....the take away point was not there......even if there was no "family history"......where is the story about genetic testing to identify risk in the children.....that would make for a great discussion or follow up......Is it ethical to test children for this risk? The American College of Medical Genetics would say, "No"

So what do you think???

Does Mr Kammerer have no family history? Does he carry a gene mutation? These are Bayesian questions that need to be answered......we know his pretest for having a family history is 60%...... we also know his likelihood of having a mutation in one of the 3 genes for EOAD (PSEN1, PSEN2, BAPP) is approximately 40% (Low end estimate).....

So do you think he should have seen a healthcare professional to offer genetic testing?

I would say yes. This is one of the times when a rudimentary collected family history may fail us, but perhaps a professionally collected one would show something...

So would a SNP testing identify this risk???? Not most of the Chips.....More importantly, do you really want to get those results in your "home office?"

The Sherpa Says: This genetic testing business is confusing. Not exactly what I would say could be sent out into the world without some training wheels......Not to be "paternalistic" but what if this SNP was on the CHIP.....soon we will have really cheap whole genome analysis and IT WILL be on that.....we have to have a serious discussion of how we can create tools to help us.....not replace us....before the public gets hurt.

Sleep on it.......Nawhhh

That's the advice I get......often.....Sometimes I take it, sometimes I don't........

My friend has pointed this out several times.......In fact in my last post, my generalizations lead some people who I wasn't even talking about to get upset. I am sorry about that. But it is no big surprise, the Sherpa has managed to piss off enough people to play out Carly Simon's song...........

You know the one......

You're so vain, you probably think this song is about you

You're so vain, I'll bet you think this song is about you

Dont you? dont you?

But in this case it is a blog post......and the unnamed source is revealed........a little company on the outskirts......To be is not about a man......and it is not about someone named Hsu or a company named 23andMe. It is about a company whose marketing tools include fooling the consumer into thinking family history catches less than a SNP scan........I will do what Carly Simon did.....indicate that a letter in the answer is "E"

But I am right and maintain, properly gathered family history has been studied for decades.....GWAS/SNP testing......less than 5 years......

This is why you can't algorithm out genetic counselors, someone needs to track down and verify these histories, and with the geneticists too busy to think straight, someone needs to do it.......until turns out there are many people working on creating social networking of family medical histories.......brilliant would absolutely remove the burden of healthcare workers actually doing it....if each patient enters their own history and links to other family members......we then have a self-report of medical history tree.....which is way more accurate than self reported family history....This is the type of thinking that will lead to earlier diagnosis.....through a well studied mechanism.....You may be too late for that one, but let me give you another.....

Rather than invest all that time working on algorithms to pump out reports on barely valid data, we should have more people in silicon valley working on real tools to move personalized medicine forward......yeah I said it.......want to save healthcare? Find a way to auto medical code thus removing billions of dollars spent of healthcare coders each year. What's a coder? Let me explain..........

To get paid by insurance a doctor has to tell the company 4 things.

1. Who the patient is.....the policy number

2. Who the Doctor is.....the National Provider Identification number

3. What the patient has.......the International Statistical Classification of Diseases and Related Health Problems Number (ICD-9)

4. What was done on or to or for the patient...the Current Procedural Terminology Code

With these four things in hand an insurer can approve or reject a what is asked or pay what the insurer thinks is fair......

What's the problem? People go to school to learn how to do coding for doctors....why? If coded right, the doctor can collect more money....If coded wrong the doctor makes less......

Doctor's hate menial tasks like this, so they spend their hard earned money on coders, but I am about to let the Valley in on a secret......sorry coders, but your days are numbered....

Coders make between 35 and 50 k per year. Not a lot per person, but if you come up with a program to do the coding, you could save a doctor that much per could end up saving a hopsital, which often has 10 of these guys on staff 500,000k per year....

There are currently a little under 100,000 of these people at work in the healthcare system.....100,000 at 50,000 USD you see where I am getting......that is precisely 5 billion dollars A YEAR!!!!!

Betcha not many people know that!!! This could be a 2.5 billion dollar a year company, instantaneously, not ever needing to create a market......Like DTC genetic testing has to do....

I have tech compatriots who say that the DTC genetic testing is the kernel of thought that tech feels is just the start of the healthcare revolution......

I think, man.....why didn't they put Navi or 23andMe's millions into a coding company......

That would be the start of the true healthcare revolution.

....Here's a hint, We ARE an expert society, we outsource things to experts, when we can, we try to replace experts, but that rarely can happen. Instead we should focusing on automating menial coding...This empowerment movement would come quicker and the billions in GDP would come sloughing off if we can do one thing.....find a way to remove everyone from healthcare that doesn't talk directly to a patient for the purpose of diagnosing and treating them........If you do that, the GDP spent on healthcare would drop to 8% guaranteed. Here's a hint, don't pick on a field of experts first....all you will get is push back. Which is why ASHG has opened another front on DTC.....

Go take the tech money and pick on the operators, administrators, human relations, custodial, marketing, public relations, coders and everyone else that spawned from providers not wanting to do it......rather than decide to push slightly scientific tests on a scientific field that demands the highest levels of accuracy......Early diagnosis happens more often when a doctor has the time to spend with a patient. Not from a panel of SNPs......most of the time....

The Sherpa Says: True, empowerment can be a good thing....but if you empower healthcare practitioners with a 5 billion dollar bonus for spending 5 more minutes with each patient instead of worrying about coding, then we really could realize personalized medicine.........

Thursday, November 13, 2008

Family history misses what?

In the last two days I have been fighting off false claims from certain employees of certain unnamed DTC genetic testing companies. Their claims/anecdotes.......

"Family history is not that misses alot.....which is why SNP testing is superior"

Huh???? Other claims "The false negative rate on family history is surprisingly high....which is why need SNP testing"

Says who?

I decided to take matters into my own hands........I turned to pubmed......

Maybe they were right? Maybe there was a whole set of data implicating that a properly ascertained family history misses risks.......especially controlled for environment. Why controlled? Any idiot knows that if you smoke, eat poorly and don't exercise you are likely to get a chronic disease even if it doesn't run in your family, so that doesn't really count as a false negative....I would be surprised if any one did this set of studies, but nonetheless I looked at this the scientific way......lit review.....

I first just searched family history.....what did I find? 54,000 articles.....phew.....someone has actually studied family history ;)

For interest sake how many GWAS papers are there? type in GWAS and you get a whopping 79.........hmmmmmmm...let's say I missed half.....that still is 160 VERSUS 54,000

Give me a break.......

One family history study reported on college freshmen girls who had a family history of drinking problems....guess what? They ended up drinkning more......There's a shocker!!

But seriously, I want to know how often Family history falls short. There must be something to it I suppose...why else would most physicians report "Family History Non-Contributory" on history and physicals? I suspect it is the fact that non-contributory means "I can't interpret or take it, therefore it contributes nothing to my assessment"

I do know that often with strong monogenetic disease you can get a negative family history.....especially in the case of new autosomal dominant disease or recessive disease.....but this is often because these patients die before they can have kids.....but in heart attack or multiple sclerosis or even diabetes, the reduction in fecundity can't be that strong......

We even see reports in response to chemo and cancer stage having family history inplications....

Among patients with stage III colon cancer receiving adjuvant chemotherapy, a family history of colorectal cancer is associated with a significant reduction in cancer recurrence and death.

So is it true? Is my equation Genome + Environment = Phenome + Metabolome hopelessly proven wrong???? You see, I say Genome + Environment is roughly equal to.......Family History

Provided that the environmental component is not greater that the genomic component this should work out pretty nicley.....unless of course you move to Chernobyl or decide to live in a Benzene factory....

So could I be wrong? Could Family history be non-contributory......In 3 cases I say yes....

1. If you are adopted, estranged or "just didn't talk about it"

2. If you cannot obtain medical records to verify self report of family history

3. If you believe in spontaneous generation

In Number One, that is likely to change as the environment of sharing health information changes.....I already see it.......30 year old women know family history better than 60 year old women do.........

Well, aside from these 4 topics.......not a single report of family history being totally useless

1. Rare chromosomal anomalies that occur in less that 1% of the population

2. Rare monogenic disease

3. Congenital Anomalies

4. Severe Trauma

But other than that......

54,000 articles vs maybe 160 articles.......Family history wins.....just about everytime.....and in common chronic disease the evidence is overwhelming.....why? Often multifactorial disease relies on multiple genetic combinations, inherited together....what an easier way to inherit these combinations than when passing them on through families.....

So the next time someone tells you that SNPs are better than family history you tell them......54,000 articles is a lot more to go on than 160....unless of course they are talking about the 4 categories where it is not so useful......

The last time I checked......that's not where DTC is.....

The Sherpa Says: Anecdotal evidence of n less than 100 is highly suspect and is likely to be used as a marketing ploy and to fool you......The "Sound of Science" is merely just the sound of silver tongued scientific shennanigans and Fads........Don't believe the hype....Family history IS the cheapest Whole Genome Analysis we have.........Not Family Genome Scans......Family History, plain and it has 54,000 Articles of research 270 times more study than SNP scans.......

Sunday, November 9, 2008

Burrill and Company Personalized Medicine Meeting

For all those people "In the Know" The Burrill Meeting is THE meeting to attend if you want to gain insight into the future of where Personalized Medicine is heading. Last year I was unable to attend but Wired had a good breakdown. This year is the 4th annual event and guess who is invited to speak........your friendly, neighborhood Gene Sherpa! I am blown away and extremely excited to be a part of this. Why???? Burrill knows where PM is at and where it will be.

Last year someone said

"Biomarkers, the genes, proteins, and other things that personalized medicine products measure, can initially appear to be strong signposts that forecast how a disease or treatment will work out, but many of the sophisticated scientific indicators prove worthless to doctors. Several of the panelists referred to markers that are truly useful and easy to identify as "low-hanging fruit", which seem to be rare commodities in the real world. "

Hmm.....I wonder if Kleiner thinks that way???? They should. This is where the puck is going to be for quite some time. I do think we will proceed to some higher level stuff including systems biology and physicians turning into genomics experts, but that will take some time. So while we are working towards that, let's not kill the goose for a few "golden eggs"

That is why the Burrill Meeting is so important, because industry will finally have the chance to discuss the barriers and investors will have the chance to hear about them....Putting Personalized Medicine into Perspective is key to guiding right investment, especially in this environment.

So do you want to know who's coming to dinner? How about the agenda?

Here are the Heavy Hitters/CEOs

Mari Baker CEO Navigenics
Linda Avey pulled out :(
Steve Burrill, no further explanation's his party!
Mike Christman CEO Coriell Institute for Medical Research and the CPMC!
Randy Scott CEO Genomic Health
John Sninsky VP Discovery Research Celera
Dean Sproles CEO Iverson Genetics Diagnostics......Dean is my age!!!
Timothy Thompson CEO Proventys (Ralph Snyderman's Baby)
Jeffrey Trent President T-Gen(Where Dietrich Stephan took sabbatical from)
Peter Vitulli CEO Sciona
Robert Wells, yes the founder of the Personalized Medicine Coalition
William Young CEO Monogram Biosciences

Now for the Physicians

William Wachsman Heme-Onc UCSD
Gary Vygantas Senior Associate Burrill
Eric Topol Cardiology Scripps, Yes. the original Maverick! This is the guy that motivated me to just do it!
LTC Alexander Stojadinovich, Surgeon, Walter Reed Hospital, USMCI. The Colonel is in the know, so follow or get the hell outta the way!
Bruce Quinn, Policy speciaist with a keen understanding of Medicare Billing and Coding
Franklyn Prendergast, He is Genomic Medicine at Mayo!!!!
Steven A.R. Murphy, Geneticst, Internist, Yale, the other Maverick, President Helix Health of Connecticut. Chief Medical Officer TotalDx.
Robert Monroe, Pathology, BioImagene
Asif Dhar, Deloitte Consulting
Susan Desmond-Hellmann, Genentech, Heme-Onc

All the rest of the fantastic speakers can be found here

Stay tuned for the coverage......I will be on the ground reporting from San Fran!!!

The Sherpa Says: Meetings like this energize the basecamp. Won't you come join the climb?

Saturday, November 8, 2008

God Bless Michael Crichton, Here Comes Google.

I want to take today and Sunday to reflect on the vision of a fantastic writer a true futurist and a wonderful physician. His Name is Michael Crichton MD. Yes true, he did write some fantastic books....but in each of them a true moral being told......

Just because we can do something, doesn't mean we should.....Even more importantly his stories revolved around those who make great discoveries and how they become corrupted by fame and avarice.

His words are most important in an age when everything is "Science" I actually see Michael reminding us of how we can't let, false science be pushed forward as truth. Never more is this evident than in the "Best Invention of 2008"

Today the Wall Street Journal agrees with my point.

You see, I have mentioned Dr Crichton several times in the past.....a Graduate of Harvard Medical School and a lover of science and medicine, he is quite a role model. From the WSJ...

A medical doctor by training, Crichton knew better than to treat scientists and technologists as a priestly class, immune from temptations of fame, profit or power........As a result, Crichton was sometimes accused of being a Luddite. In fact, he was a champion of good science, and never more so than in a 2003 lecture at Caltech, hilariously titled "Aliens Cause Global Warming."

I too have heard those words about my blog and my ideas. It is the unreasonable man who challenges "conventional wisdom" upon whom the world depends for change. Bad Science is no replacement for Lack of Truth....we must be very careful as we push forward advancing healthcare with technology and "science" We must be very sure that if we are to put something forward for patients that the benefits clearly outweigh the risks......And if we are to have no chance of healing we at least Do No Harm....

That was Dr Crichton's message. I am so very sad to see him pass......his 26 novels and numerous screenplays will be a forever reminder of how

"As the 20th century drew to a close," he warned, "the connection between hard scientific fact and public policy became increasingly elastic. In part this was possible because of the complacency of the scientific profession; in part because of the lack of good science education among the public; in part because of the rise of specialized advocacy groups which have been enormously effective in getting publicity and shaping policy; and in great part because of the decline of the media as an independent assessor of fact."

This is why I formed HelixGene with Drew Y, This is why we started Helix Health of Connecticut, This is why we volunteer to teach Genetics to High School Students, This is why we always have to remember that "Bad Science is no replacement for absence of evidence"

I see the storm clouds rising, people looking to make healthcare efficient, people who didn't study the biological sciences....instead they chose computer science.....I just hope and pray we can demonstrate that science can be just as bad as poor programming.......

Need further proof they are coming? From the WSJ....Bret Swanson

On health care, let's face facts. We are not going to "solve" the entitlements crisis by gouging American producers to pay for the current Medicare/Medicaid abomination. Much better to transcend the issue with medical innovations and an entrepreneurial, consumer-driven market where more physicians go into medical technology, more nurses replace doctors, more technologies replace doctor visits, and, with properly-aligned incentives and real prices, more citizens take better care of their own health and thus their pocket books. The only way to escape current predictions of scarcity is the unforeseen abundance that entrepreneurship can bring

The Sherpa Says: Technology is not is not even bad just is....and when you pair that with Bad Science....well, then you have some problems.......Oh Michael we need you now more than ever......

Thursday, November 6, 2008

Nature is so Wrong!

Nils over at SciPhu has decided to stop posting about DTC and his stance. Why would such a great scientist/blogger decide enough is enough? Nature made him do it...Huh? Yes Nature and its eloquent arguments about personal genomics......

From Nils

"I have voiced opinions on this too, but have decided to desist more arguing (for a while) after reading this editorial in Nature biotechnology"

I am going to deconstruct the arguments in Nature right Now!

1. We need to move from late to early diagnosis

It is virtually impossible to conceive of a sustainable form of healthcare that operates as the current systems in industrialized nations do. At present, healthcare is based on the late diagnosis of disease and the division of diseases into a few categories based on some overarching gross similarities. And it firmly places physicians as the central gatekeepers of information.

So this argument says.....That in the current system...

1. Doctors cannot do early diagnosis

2. Patients should be responsible for early diagnosis

3. The current system is not adapting to early diagnosis

Why is this nature argument a fallacy?

1. Doctors have been doing earlier and earlier diagnosis.....Ever heard of Pre-Hypertension or Pre-Diabetes? These conditions are getting detected at earlier and earlier stages, physicians ARE doing a better job of finding this out.....

2. Patients can interpret laboratory tests and should because we don't have enough healthcare providers to interpret the data......Huh? Ok, so I propose that we have 2 levels of care, the one level in places like Harlem where it is an under served community. We have a patient take a blood test and then have the patient interpret the results. Heck we could give them a computer and Internet.......Good luck! Oh and the other system where doctors and other healthcare practitioners decide to practice and deliver care.....Nice argument.....

Patients should not be responsible to defend themselves in a court case because they can't afford an attorney, they shouldn't be responsible to design their own homes because they can't find an architect, Hell, there is even H&R Block for people's taxes.....Why are we trying to cut out healthcare professionals because costs are high? I say costs are high because we don't have enough professionals...instead we have coders and healthcare administrators............Would you expect a patient to interpret a liver biopsy? What about an X-Ray? So why in the hell would you say they should interpret their own genetic information? Garbage argument.....

3. Huh? The system is adapting to early diagnosis and adherence to standards of care. Ever heard of PQRI? What about JCAHO and the preventable outcomes evaluation? The system is working to prevent errors and diagnose early.......Just b/c it's not enough doesn't mean you destroy the system.....

2. To do this we need find ways to utilize the potential unleashed by large scale analysis of genetic-material.

The healthcare of the future, on the other hand, if the technical potential to provide personalized medicine is ever to be realized, will probably require a greatly expanded emphasis on diagnosis and monitoring, early and subtle intervention, monitoring of the impact of intervention, and gradual adaptation of treatment with the evolving physiology, metabolism and lifestyle of the individual.

So this argument says that we don't have enough people to monitor the care of patients, so we scrap that system and put everything in the hans of the patient.....over the internet I suppose. There are 3 things wrong with that.

1. What happens when a patient mis-diagnosis him/herself? What happens when the ignore the "Service engine soon" light? The same people avoiding healthcare now are precisely the ones who have diabetes diagnosed at a late stage, or the patient who comes in 5 days after his heart attack.

2. What's to say the the Internet will motivate that person to change? Doubtful at best.....Patients need professionals to monitor their health....end of system can serve all.....even crazier.....who maintains privacy of that patient?

3. Even crazier....who does a patient sue when the diagnosis is missed???? The system?

Nature's solution?

3. But, the medical professionals and healthcare systems do not currently have the capacity to adequately respond.

Faced with this huge expansion of data on ‘my’ health, it will simply not be affordable to maintain our dependence on medical gatekeepers, whether they are physicians or genetic counselors, without individuals taking a much greater responsibility for their own wellbeing. Whether the medical establishment likes it or not, it will be too cumbersome and too expensive to conduct personalized medicine if all diagnostic-to-therapeutic decisions depend on doctors.

Ok, mythbuster number 3.....the amount of data relevant to a patient's care and health WILL NOT CHANGE THAT MUCH IN THE NEXT DECADE!!!!!

But you could greatly overwhelm the system by introducing bogus bits of information that have absolutely nothing to do with health outcome.....Don't believe me? Did you read the incidentalome written in JAMA. Russ Altman and Zak Kohane (advisors to 23andME wrote this)

Here's the excerpt:

Genomic medicine is poised to offer a broad array of new genome-scale screening tests. However, these tests may lead to a phenomenon in which multiple abnormal genomic findings are discovered, analogous to the "incidentalomas" that are often discovered in radiological studies. If practitioners pursue these unexpected genomic findings without thought, there may be disastrous consequences.

First, physicians will be overwhelmed by the complexity of pursuing unexpected genomic measurements.

Second, patients will be subjected to unnecessary follow-up tests, causing additional morbidity.

Third, the cost of genomic medicine will increase substantially with little benefit to patients or physicians (but with great financial benefits to the genomic testing industry), thus throwing the overall societal benefit of genome-based medicine into question.

They said why are the advising a company which puts all that data out there???? Good question.....

The Sherpa Says: Because the system can't handle the data we should throw out the interpreters of the data????.....Listen.....this isn't Cobol you freaking chuckleheads! This is years and years of scinetifically proven medical physiology, biology, and healthcare which doesn't just get replaced with a better model.......We may Augment....but never completely replace....until the evidence tells us what we are doing is incorrect we shall continue with what we have.

Wednesday, November 5, 2008

Genetic Test or Family History? Which Matters More?

I would say that when used in combination a 3 generation family history and appropriate genetic testing are probably the best tools we have to identify risk for and diagnose genetically linked disease.

So what matters more to patients? What risk means more? The results of a genetic test OR their family history. Hsien Lei touches on this briefly at Eye on DNA, but the interpretation she provides is not exactly what the article said or studied.....What article? Well the one I am about to tell you about...

Published in the Archives of Pediatrics and Adolescent Medicine this week an article entitled:

The article sought to study:
To evaluate the effect of the genetic risk information source (family history vs genetic test results) on parents’ concern about their own and their children’s genetic disease risk.

In lay terms, which mattered more and carried more weight when "assessing" risk by a history OR genetic testing.....
Hsien interprets this Family History of Disease Scares Parents More Than Genetic Test Results .... I wouldn't say scares......I would say concerns.....or means more to them.....
Fear was not studied in this analysis......Concern was....

The Method:

Parents first received a vignette about their hypothetical genetic risk, randomized as either a family history assessment or genetic test results. Next, parents received a vignette about their youngest child’s hypothetical genetic risk, similarly randomized.

The Vignettes:

Imagine that you have family members with a disease that causes severe symptoms in adults. Having this “family history” means that (you/your youngest child) has a 30% chance of developing this disease. A 30% chance means that 3 out of 10 people will develop the disease.
“How concerned are you that (you/your child) might develop this disease?”


Imagine that (you/your youngest child)gets a genetic test result that says he/she has a 30% chance of developing a disease with severe symptoms in adults. A 30% chance means that 3 out of 10 people will develop the disease. “How concerned are you that (you/your child) might develop this disease?”

So this clearly is a high risk gene 30% likelihood is about what the risk is for Ovarian Cancer carrying a BRCA gene mutation. "Roughly" for my CGC readers who like ranges......

The Results:

Parents were more likely (twice as likely) to be concerned about their own disease risk when
the risk estimate came from a family history assessment vs a genetic test result (odds ratio, 1.96; 95% confidence interval, 1.44-2.68).

But here's where it gets interesting.......Patients perceive the risk of their child's as the same as their own.....clearly not a mendelian concept or even a genetic concept......Even more interesting was the fact that despite this being the case 73% of the time, the other 27% actually were concerned that their child's risk was HIGHER than their risk...... have to love denial!!!!!


Positive family history of disease generated greater concern about parents’ own risk of inherited
disease than did genetic test results.

The Sherpa's Conclusion? People don't know what the hell they are doing when analyzing genetic risk. Nor do they know what the hell they are doing analyzing multifactorial disease risk in pedigrees....

So I ask you....."Should we expect them to?" Isn't this the exact reason why we have geneticists and genetic counselors? Our job is to interpret family histories and genetic test the doctors' case they interpret full medical history, perform physical examination and review of systems and evaluate other lab values oh, and medication history too.......

Why should we expect patients to know or understand these concepts? Oh, I know why.....because we are trying to thrust onto themselves the diagnostic and interpretive responsibilities in some crazy screwed up way to save costs for the American Healthcare system.....By doing non-clinically valid DTC testing which will be pushed down our throats by Time magazine and the PR firms of the silicon valley DTC firms.....

Or at least that's what some one in this field told me......Personally, if you want to save healthcare the coders, HR departments, compliance people, essentially fire everyone who doesn't lay their hands on a patient or handle their lab specimens.........That's where the fat is NOT in direct care.....

The Sherpa Says: Pedigree analysis, Bayesian Interpretation, Molecular Biology and Genetics are not taught in high school...why In the hell should we think everyone will be able to use DTC testing, which doesn't even throw family history into the mix......Silly....real silly......Stick with your Sherpa.....don't try to climb mountains on your own.....

President Obama and the Genome

Now that we have a new president many may wonder what will occur in the realm of personalized medicine. Well, the short answer is ALOT. Several things that the democratic majority in the house, senate and executive branch plan to enact.

1. Senator/President Elect Obama's Personalized Medicine Bill will likely pass. What does that mean?

He has proposed an interagency task force on genomics research, modernize FDA review of genomics tests and expand support to genomics researchers, including funding and creation of a new mechanism to allow researchers across the country to access and analyze genomics research. As president, Obama will continue to support advances in personalized medicine to help ensure early detection and treatment of cancer and other diseases. The bill appropriates $75 million a year to establish a National Biobanking Initiative and another $26 million to "Realizing the Potential of Personalized Medicine".

This means greater regulation in the field....including DTC testing. Too bad for Rupert Murdoch but we are actually going to require evidence for testing...

2. Increased funding for Personalized Medicine in Oncology

The Obama-Biden plan will help our health care workforce grow by expanding funding for loan repayment, adequate reimbursement, grants for training curricula, the Nurse Reinvestment Act of Title VIII of the Public Health Act, and infrastructure support to improve working conditions. The Obama-Biden plan to double cancer research funding will also help recruit and retain clinical researchers who specialize in cancer by providing adequate funding for oncological study.

3. Obama will likely be having Francis advise him....The big geneticist from MY institution! Can only mean good things

The Sherpa Says: The tribe has spoken......Look forward to seeing you in San Fran!

Tuesday, November 4, 2008

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 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 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 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 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 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

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.