The New BRCA and SubSegments of a Segment

First and Foremost,
To all women who have hereditary patterns of Breast Cancer, but have a negative BRCA work up....there is new information which deCode has released in Nature Genetics. I was very excited about this and look forward to some significant replications.

From a recent MarketWatch report
Common variants previously discovered by deCODE on chromosomes 2q35 and 16q12 are together involved in an estimated 25% of ER+ breast cancers. The analysis in today's paper also reveals that a fourth known set of variants, located on chromosome 10q26 and accounting for approximately 16% of breast cancers, appear to confer risk exclusively of ER+ tumors. deCODE is applying these variants as the basis for a DNA-based reference laboratory risk-assessment test the company plans to launch in the coming months

The rationale for such testing is all the more compelling in ER+ cancers, since drugs such as tamoxifen have been shown to be successful in preventing as well as treating these cancers, and other drugs now in development may prove to be safe as long-term prophylactic therapy as well.

This is huge news. Imagine being able to pinpoint risk for ER+ breast cancer. We already have medications which can reduce the risk of these cancers!!!!

I think the excitement was there until......I looked at the Odds Ratio! So to recap, "New genes for breast cancer, but the increased risk is only 20% above the population". In fact, that was the largest effect. So I want to say Ho-Hum about these tests and probably will. But, the American Cancer Society is recommending MRI for those who have an increased risk for breast cancer. Notably once that risk is 25% about the population risk. This MIGHT put people into this category....I say MIGHT!

So this leads me to my next question is this a medical test? Or a recreational genomics test?

A report by BioArray News..

By Justin Petrone
Hoping to insulate themselves from regulatory pressures from at least one state health agency, some direct-to-consumer genetic testing services may position themselves as disease-risk testers while others may focus more on recreational genetics, such as determining genetic ancestry.

Thus, I ask what testing company could insulate themselves when it is obvious that even ancestry testing can reveal medical data!!! Personally, I feel that when applied...any genetic test can identify medical risk.

So is all genetic testing medical? To subsegment in a hope to protect from legislation is disingenuous at best. The government is going to come down hard on these companies... All in the name of protection of the public. Why? Because the public like the physician is not quite ready for this.

Blaine points this out over at The Genetic Genealogist.
Some concept questions were failed by over half of participants. Which only reinforces the public's lack of understanding and susceptibility to hype. Much like the WSJ hype on this finding. Shame on Marilyn over at the WSJ for not reporting the mild increased risk and instead lumping this in with the BRCA gene risks!

The Sherpa Says:
The public is anxious to buy into hype. Companies are anxious to build hype and it seems all too convenient that the press is willing to help. The path is getting complicated. Let's use the principles on this one. 1. Await replication 2. An Odds Ratio less than 2 is not that impressive 3. Don't believe the reports, unless translated by a professional.

Oprah, Oprah, Oprah!

In a gut wrenching episode of Oprah the other day Randy Pausch spoke about pancreatic cancer. It is a scary disease as almost everyone dies from this cancer AND it is so difficult to detect. He is correct, we know so little about pancreatic cancer. We know so little about its pathoetiology(Cause of). We are learning a little about pancreatic cancer genetics.

But what scares the hell out of me is when a well respected pulmonologist and critical care specialist comes up to me today and says "My wife's father had pancreatic cancer. She's scared to death about getting it. She saw on Oprah a genetic test and something called 23andMe. Can you help me get these tests?"

Woah......Big fella!!!! I spent 30 minutes going over familial pancreatic cancer, doing a quick family history and coming up with the fact that there is minimal risk in this 40 year old woman. Other than sever neuroses from watching Oprah and being scared even more.

Frankly, I think Oprah is wonderful for pointing out revolutionary breakthroughs. But, last time I checked, 23andMe, Navigenics, etal. are not testing for the more common causes of familial pancreatic cancer.... BRCA2, Melanoma-Pancreatic, HNPCC, etc.

He then says "But can't we just get one to put her mind at ease?" I said "Well, what she needs is an evaluation" He says "But she just wants the test." That is when it hit me like a cold flash of water in the face. Why does she only want the test?

That is what we need to answer. This answer will lead us to comprehending other questions like

1. Does she understand what the test does?

2. Has she gotten an explanation of the issues of testing?

3. Is she aware of the costs?

4. Did she have a bad outcome with a counselor or doctor about genetics before?

5. Is she aware of genetic evaluation services?

We could always point her to a site like GeneForum for a little FAQ on gene testing. Or we could take the time to sit down and explain things to her. This is directly related to My Last Post with Beta Blockers for everyone. Doctors don't have that 3 hours to explain. This is the same damn reason people with futile illnesses are languishing ventilators in our ICUs costing millions of dollars for incurable diseases, that ultimately end in death. Doctors don't have the time to explain. How in the hell can we give them time? Teach the consumers.

This is precisely what we need to do. The ACMG has issued a statement which Hsien covered nicely. Also it seems people like DNADirect are moving in this direction with Virtual Consultation.

Heather Shappell over at Informed Medical Decisions, a leading expert on phone consultation and leveraging of services and I bot wonder why do we need 20-80 pages of report to explain what can be done so simply in person or via the phone. While I think the virtual is a great thing to leverage our services...there is something to be said of a nice handshake. I have peeled through a few 80 page DTC testing reports. Lots of fluff and no real information. The pie charts were nice though.

The biggest crux of all genetic testing should involve some trained clinicians. This is emphasized by the ACMG statement.

That is why it leads the statement

1. A knowledgeable health professional should be involved in the process of ordering and interpreting a genetic test.

The Sherpa Says:

I bet if this lovely woman knew the limitations and likelihood with testing she would not want to go it on her own. Too bad her wonderful physician husband can't give her that counseling. My concern is that Oprah may not have indicated the use of genetic evaluation by a skilled clinician PRIOR to testing. And we all know what Oprah says is seared in the minds and hearts of MOST of America. Oprah, give me a call. We would love to educate you and your viewer about the promise of Genomic Medicine.

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.

Happy DNA Day!!!

Lots of great posts on this DNA Day. First, I would like to tell Misha at GenomeBoy....Doubting Thomas was eventually one of the greatest supporters.... This is in response to my post yesterday. I think he might have called me Sherpa Buzzkill if he wasn't my friend.

I love that guy....seriously. Here's a man who has the paper and is a hell of a writer. Now he throws caution to the wind and signs up for the PGP. You gotta admire the courage. Pre-GINA mind you! But after the clarification of my exaggeration of the PGP informed consent profile, I thought it would be good to clarify the policy of the Delaware Valley Personalized Medicine Project. For full disclosure, I sit on the ICOB where we will meet and determine whether a SNP is medically actionable. The first meeting is in June.

The view from 30,000 feet is

Technical:
1. The databases are designed to keep genetic data and phenotypic data separate from personal account information.

2. Storage of certain personal information such as account information is encrypted.

3. The network perimeters are protected with firewalls.

4. All connections to and from our web portal are encrypted with a VeriSign SSL Certificate with Extended Validation (EV) and server-gated cryptography (SGC). This is the most trusted and secure option for SSL.

5. Internal and external audits of perimeter and software code security are performed.
Employees' use of the databases is monitored and records of all access to personal information are maintained.

Physical:

1. Access to the building housing the Coriell data center requires an electronic keycard badge ID for entry into the facility.

2. Physical access to internal servers is restricted to authorized personnel.

Administrative:

1. Access to personal information is restricted to certain employees for limited, approved purposes based on their specific responsibilities.

2. Annual privacy and security training is required for employees with access to personal information.We meet HIPAA IT requirements

For more information about this wonderful project take a look at their site and at my posts.

I am going to skip the recap for now. I will post the recap tonight.

The Sherpa Says:

Thank you to the readers who pointed me toward the San Jose Mercury News. Very interesting article.... If GINA gets enforced like these laws, then we can expect some very good patient protection. But we still need protections like the DVPMP

Timely Release and A Unanimous Vote

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

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

The notable item...

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

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

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

GINA first, then the floodgates open!

When preparing my plan for genomic medical services I saw one HUGE barrier.

That barrier to entry was NOT

1. The shortage of providers

2. The lack of educated physicians

3. The lack of evidence base

4. The cost to enter

It is and soon will be was

Passage of Federal Legislation Preventing Genetic Discrimination.

Ladies and Gentleman. Tomorrow, the 24th of April 2008...that barrier will be blown away.

So here's the question to congress. "Are you ready for the rest of the fly by nights entering the game?" Cogent indicated that a full 75% of Americans would be interested in genetic testing for health benefits IF AND ONLY IF......There was federal legislation protecting against discrimination.

That day has come.

The Sherpa Says:

I find it wonderful that the 24th medical specialty will find its patients on the 24th of April. Even funnier is how the Sherpa's life revolves around....the 24th. What is going to happen the day this bill gets signed into law? Stay Tuned....

GINA will PASS! Thanks GTO!

I was eating lunch today at the Lotos Club with a good friend and mentor from SF today. This gentleman sits on corporate boards and is a tremendous advisor. Do you know what he said to me? Mind you, he always seems to have an answer and the experience to back it up. Today he said "I don't know" That's right, he said those 3 words. I was blown away. He and I agreed that the only reason was simply because.....No One Knows. I liken our venture into genomic medicine much like the microsoft and internet ages. No one knew...they were making up the rules as they went along.

Today, it is the same. Try to play with fire? You get burned. Try to find money for the perfect model and you get beat by someone rushing to market with something less than perfect....who then ends up buying a competitor. Jeez, genomics is the wild west. But I am back East!

I think we are well on our way. But legislators are stepping in and making the playing field bumpy for the non-medical types. Just as they send out threatening letters, the NY Times posts that Doctor No is going to say Yes. It is reported that GINA will have it's day in the Senate!

I have been saying forever that if you pass GINA, all the physician misconceptions of genetic discrimination will be washed away. That being said, there is some good advice here. Always consult your geneticist or counselor regarding these implications.

So as my poll closes tomorrow, it is pretty clear the majority lies with GINA getting passed next year. I voted for next month.....To quote my Friend Happy Gilmore "Somebody's Closer ;)"

So with GINA on its way, it is only a matter of time before we have more people enter this industry. Speaking of industry? Who is going to the Beyond Genome Conference in June?????

I will be speaking there about the fusion model of genomic medicine. Don't miss it! All 20 minutes of it ;)

To close on a Snarky note

My friend and I were eating and I said. Imagine what it will be like in 20 years? We will be the old timers. He said "Yeah, it'll be just like the internet crowd. You will probably be saying 'Man back then it really was amateur hour!'"

The Sherpa Says:

GINA is merely one hurdle.....now we really have to start with education.....of everyone. We must not let our curse of knowledge lead us into thinking everyone can do what we do. Who wants to help me start teaching? Call me. Oh, and Misha....I hope this pic meets your approval.

Are you Serious?

While I was lauding Misha ( One of the 10 PGP'ers) and correcting some misconceptions about the PGP informed consent process....something much bigger was happening. I don't know how I missed it...but I did...


Google Buys Into Navigenics!!! That's right...Google now has a stake in 2 of the big 3.......Me? I am the 4th...merely a little guy. Our humble abode is now protected thanks to the NYS and CT Attorney Generals...for Now, well at least until Google can buy New York State.


From Business Week!!


Size of Investment Not Disclosed
Calling 23andMe an example of a company "generating a whole new batch of information of interest to a broad range of people," Pederson says Google wants to extend its capabilities into genetic testing. The precise path and business contours of the emerging gene-testing market remain unclear, but if Navigenics succeeds it "will generate a lot of a very new type of information with potentially far-reaching value," says Pederson. "We felt it was important to get involved now, at the early stage, to better understand the information generated by this fast-moving field."





Did anyone see my post about the Master Plan????? Did anyone watch the Movie??

Read an excerpt from the story



"The Google Story"

Sergey Brin and Larry Page have ambitious long-term plans for Google's expansion into the fields of biology and genetics through the fusion of science, medicine, and technology. . . .One of the most exciting Google projects involves biological and genetic research that could foster important medical and scientific breakthroughs. Through this effort, Google may help accelerate the era of personalized medicine, in which understanding an individual's precise genetic makeup can contribute to the ability of physicians and counselors to tailor health care treatment, rather than dispensing medications or recommending treatments based on statistics or averages.


"We need to use the largest computers in the world," Venter said. "Larry and Sergey have been excited about our work and about giving us access to their computers and their algorithm guys and scientists to improve the process of analyzing data. It shows the broadness of their thinking. Genetic information is going to be the leading edge of information that is going to change the world. Working with Google, we are trying to generate a gene catalogue to characterize all the genes on the planet and understand their evolutionary development.




Geneticists have wanted to do this for generations."Over time, Venter said, Google will build up a genetic database, analyze it, and find meaningful correlations for individuals and populations. . . . Google's data-mining techniques appear well-suited to the formidable challenges posed by analyzing the genetic sequence.It has begun work on this project, but has not been required to disclose any information about it publicly since the work has no impact on its current revenue and profits."




People will be able to log on to a Google site using search capacities and have the ability to understand things about themselves as they change in real time," Venter said. "What does it mean to have this variation in genes? What else is known? And instead of having a few elitist scientists doing this and dictating to the world what it means, with Google it would be creating several million scientists."Google has empowered individuals to do searches and get information and have things in seconds at their fingertips," he went on. "Where is that more important than understanding our own biology and its connection to disease and behavior? With Google, you will be able to get an understanding of your own genes. Google has the capacity to do all of this, and it is one of the discussions I have had with Larry and Sergey."


My business colleauges say "A rising tide raises all ships" But I have to tell you, I am a little worried that they want to end around healthcare not just end arounding IRBs.


My guess. Google will acquire every single bit of DNA database they can get their hands on. Why? Knowledge is power. And they want both.


The Sherpa Says:


Since this is an industry...couldn't we liken this to the XM/Sirius merger? In all seriousness. These corporate genomics companies see medical genetics as a non-scalable model....so they want to get rid of it all together. Flying to the top of the mountain does not get you back down it. I plead with Google, please get some medical guidance. Please!!!!

Piracy or Privacy? Some Thoughts.

First I want tell everyone how absolutely amazed I am by Misha Angrist. I don't know if you know who he is. But I now tell you that you must. He is one of the PGP 10. I know, it sounds alot like the Oceanic Six...but seriously Misha is way better looking than Jack!

I also want to apologize to Misha....I over-reacted with the article. What article?

The article now in Nature Genetics Reviews addresses the topic of open-consent which has popped up again! Daniel over at Genetic Future points out this excellent article written by "Jeantine E. Lunshof1, Ruth Chadwick2, Daniel B. Vorhaus3 & George M. Church4 "About the authors"

In this beautifully written paper they expound on several issues facing genomic technology and science. From the article:

Current developments in genomics challenge the established framework of biomedical ethics because the empirical facts of the genomic science change too fast for the reflections of ethics to keep pace with.

Whoa!!! Isn't this precisely what we were thinking about when the HGP began? Didn't we anticipate this deluge? I think we did. Science should never trump ethics.....EVER!!!

These developments have ethical, legal and social implications that call for strong cooperation between science and humanities6. While looking for approaches that can adequately address the moral and policy issues that are raised by emerging genomic technologies, ethicists are increasingly aware of the need for a shift in emphasis, even if it ultimately requires revision of key concepts in mainstream biomedical research ethics.

As long as we don't drop the Declaration of Helsinki or Call the Belmont Report trash, in the name of scientific progress.

Consent is relevant in building large-scale databases containing genotype data that are inevitably traceable to individuals, as well as in generating 'personal genomes'. What pragmatic moral guidance can be offered under these new circumstances?
In this article we argue that the reality of the new genetics and genomics urges us to abandon the traditional concept of medical confidentiality.

Just because we can't guarantee complete confidentiality, should we abandon it? Or perhaps just the concept of confidence. This could take some work ladies and gentlemen. We are talking about the social reprogramming of an entire nation!

Comprehensive data sets to establish informatics links among ten thousand to a million human genome sequences and extensive phenotype analyses are needed to effectively generate and test hypotheses, but they also enable the identification of the individuals whose DNA sequences they contain. This puts the validity of the existing consent protocols into question. If promises of privacy and confidentiality need to be abandoned, what are the implications for meaningful consent in the context of genomics research?

Whoa there! Who says we have to abandon promises of privacy and confidentiality? Perhaps they merely need to be modified?

Genetic privacy can be taken to denote a particular instance of the general concept of privacy, although often it is used as a value-laden concept that is qualitatively different from 'normal' privacy14 — a concept that presupposes adherence to genetic exceptionalism15. By contrast, we subscribe to the view that genetic privacy is just one instance of privacy.

I agree. privacy is privacy. Regardless of genomic or proteomic.

They then go on to argue that the whole system is already somewhat a sham. They mention the sickle cell trials in the 70s. The arguement that discrimination existed in a group (African Americans) where individuals existed that were carriers of Sickle Cell Disease.

The experience with sickle-cell anaemia screening in the United States demonstrated, as early as 1972, that stigmatization of individuals on the basis of their membership of a particular group is a real risk18. Whether this is based on genetic or other traits, conventional individual privacy protection misses the point. It does not work in the case of so-called non-distributive generalizations about groups in which the individual profile is indiscernible from the group profile.

They concede that GINA is a hope to help this. But I agree...the new discrimination will not be based on the color of your skin. It rests in your Copy Number Variation and your SNPs. But who is to say "everyone" will have access to your genome? Unless you are GenomeBoy

So I read on......

I did have a little bit of shuddering when I read these next 2 incongruous parts of this article.

Confidentiality implies trust in private and in professional relationships between individuals. The maintenance of confidentiality by professionals is vital to the trust in the profession, for example, to the public trust in physicians, lawyers or members of the clergy.

AND

Although, in clinical medicine, veracity is the legal norm in many jurisdictions, physicians may try to justify the withholding of information by invoking the 'therapeutic privilege'. In research, there is no such privilege, and when seeking informed consent from research subjects, distorted or incomplete information could undermine trust in researchers and in science.

So that upset me a little. Admittedly, trust is important in the relationship between a patient and their physician....but not really.........

Still though, just because someone can identify you....doesn't mean that they will. I have some problems with this argument. Do we use credit cards on the internet? Should we stop using 128 bit SSL because someone CAN steal our card info? How would shoppers feel if they were told in huge letters on the website "YOUR CARD INFORMATION CAN BE STOLEN BY USING THIS SITE?" How many companies would go belly up after that "Veracity"? The public operates under a thin veil of presupposition. All chaos would exist if this were not the case. So I give you the PGP open-consent

Open consent as part of the Personal Genome Project implies that research participants accept that:

• Their data could be included in an open-access public database.
• No guarantees are given regarding anonymity, privacy and confidentiality.
• Participation involves a certain risk of harm to themselves and their relatives.
• Participation does not benefit the participants in any tangible way.
• Compliance with monitoring of their well-being through quarterly questionnaires is required.
• Withdrawal from the study is possible at any time.
• Complete removal of data that have been available in the public domain may not be possible.

The moral goal of open consent is to obtain valid consent by effectuating veracity as a precondition for valid consent and effectuating voluntariness through strict eligibility criteria, as a precondition for substantial informed consent.

This is their Open-Consent option. It makes sense. It sounds like the credit card promise...sorta.

But what gets me is the close.....

Alternative solutions are scarce. Veracity requires broad consent in any case of collection and long-term storage of comprehensive data sets. However, an overly broad consent could become meaningless. The most likely pragmatic solution would entail maximizing data protection while informing people about its limits.............................. The role of ethics is neither that of an alibi nor of a straightjacket.

The Sherpa Says:

As long as this is what it is then I am ok with it. But if this is the introduction of SOMA, Free Love and the Bokanovsky process then I have to call it a day! Seriously is this worth a 60 Minutes episode? I don't think so. We need Informed Consent and that is exactly what it is. Does it mean no privacy? No. It means compromised privacy at best......for now! Tomorrow I will tell you about what the DVPMP is doing in this arena. Stay tuned.

Why Biostatisticians should get paid better

I am always amazed by the mathematical nature of genetics. Everyone can understand the A,T,G,C bases. The whole theory of DNA replication is easy. But let me tell you what is not. Biostatistics. Anyone who has a taken a course or two can surely back me up.

In the American Journal of Human Genetics there is a novel model for calculating Odds Ratios in Genome Scans. Why am I pointing it out here? Simple...there are several ways we analyze genetic data. This is a new way. Several papers as well as several corporate genomics have their individual way of calculating multiple SNP risk.....personally I feel that all of these should be published for peer review.

That still doesn't address my title. Why should the biostatistician get paid more? The mathematic link to genetics is huge. I am surprised there are not a significant amount of training programs emphasizing these statistical tools for physicians...But there are very few. Even the same for biostatisticians.....They are the workhorse of Evidence Based Medicine and Genomics. Why so little training in med school?

I guess we can just chalk it up to another field missed by curent graduate medical education. But don't worry, many advanced biology degrees miss it too.

In genetics there has been a shift away from the classical biostatistics to more probability based statistics. Such movements include the Bayesian changes that really started to move forward in the late 1990s. This has revolutionized our analyses.

No other field has relied so heavily on the backs of statisticians. But, Why I am commenting on how complicated genetic analysis is? Because now that we have alot of DTC testing going on, we may begin to devalue how important genetic discovery, scientist geneticists and clinical geneticists are. But even more so, we will begin to forget how very valuable the biostatistician is.

What is a biostatistician? You can find them at the Analytic Bridge....a network of "Analytic Professionals" Yes, even like us dorky gene heads, they have their own network!

So why am I posting about this on a Personalized Medicine blog? I just told you! If we did not have bioinformatics or biostatisticians, we would still be stuck with the punnett square! So today I say, "Thank You Markov Chain Guy!!!"

-Steve

They Could've used the Sherpa!

So, I am glad that I have been posting on this subject for quite some time now. It seems we all have been blogging about it. Today, Blaine points out an article at Forbes, which is further proof that someone is reading the Sherpa. Matt and Bob, sorry about slamming you before....I just needed to know where your loyalties stood. I did wonder about your journalistic neutrality. But the article you write today is neutral and shows that maybe you had read about my concerns. Thank you for putting this out there!

I hope you see the power you have to hype and over-sell. I am glad that you co-authored this piece. So let's take a looksie at what is going on...From the article

Over the last six months, New York State's Department of Health has sent letters raising the specter of fines and jail time to six online gene-testing firms that offer consumers the ability to peer into their genome to assess their future risk of getting diseases such as cancer, heart disease and multiple sclerosis. Often, it turns out, the services offering these DNA deep-dives are doing so without the involvement of a doctor. That puts them on the wrong side of the law.

The Sherpa warned them of that back in 2007. In fact I worried that these authors articles may have encouraged the companies to sell and consumers to do the deep dives!

Targets in New York's letter-writing campaign include the high-profile 23andMe, in Mountain View, Calif, (run by the wife of Google (nasdaq: GOOG - news - people ) co-founder Sergey Brin) and Navigenics, of Redwood Shores, Calif., as well as their publicly traded partners Illumina (nasdaq: ILMN - news - people ) and Affymetrix (nasdaq: AFFX - news - people ). The letters say the companies cannot perform their gene scans on New York residents without a permit. Warning letters to three more online gene-scanning firms are due to go out soon, New York says.
It seems regulations are going to be enforced. How? To Whom?
I have the litmus test for these regulations. I really wish, that rather than speak ill of me at open bar cocktail parties, these companies would have sought me out to speak about how we could do this the right way. I admire all of you (corporate genomics founders) for risking and bringing this to the forefront.....But, you all did it the wrong way. You trumped geneticists, you trumped physicians, you tried to play doctor!

And now you are going to feel the heat. Even though Spitzer is not around anymore....New Yorkers do not screw around when it comes to this!

So I ask my readers..."Why didn't these companies come seek the Sherpa's path?"

I think it is because of greed. Or perhaps the arrogance that only millions of dollars and a nice spot in SF can buy you. Well...we will recover from your follies....Back in New York we already are. And by the way, You need CLIA and NYS approval to test in New York.....D'Oh..

Or perhaps some sorry legal team gave them poor advice. You should have used my team, they knew.

Complicating matters is the fact many online gene testers, including 23andMe and Navigenics, don't actually perform the scans themselves; they are simply Web portals that disclose the results of tests performed by contract labs. "There are very few federal regulations in this area," says Elliott Stein, an attorney who represents gene-tester HairDx, which just received a letter from New York. "Unfortunately for these companies, they've got to deal with the regulations in each and every state, and often that is a judgment call."

Or maybe they thought...."Hey, after all...this is only recreational"

"Frankly, it blows my mind that someone would be saying that looking at whether you are going to get multiple sclerosis is recreational," says a New York official who spoke on condition of anonymity. The official says New York is not about to shut the services down but, "we would refer them to the attorney general's office" if they continue to operate in violation of the law.

This IS the practice of medicine, your tests are diagnosing predisease. Even if they are "low penetrance" gene SNPs. All three should never have posted health related information, unless they were prepared to practice medicine.

Simple enough. Now that you have taken your lumps, please give me a call so we can move forward in the right direction. DNADirect is moving that way and we welcome that. I hope we all can evaluate the literature in a transparent way. EGAPP is working on it and so are we at DVPMP. I hope this DNA Perspectives will help as well....Navigenics is moving this way too. So please listen, transparency is key to trust. Many are going to begin to distrust if you don't stick to this....

Because,

Now your basecamp is coming after these companies too...

California health regulators are also investigating 12 complaints from the public about certain online gene testers. California won't name the targeted companies, but notes that in the state "all genetic tests must be ordered by a licensed physician." Overall, 24 states prohibit or limit so-called direct-access testing without a doctor or other medical professional's involvement, according to a 2007 survey by Johns Hopkins University's Genetics & Public Policy Center.

I had posted on this too. Hopkins delineates this very nicely!

So Corporate Genomics........the ball is in your court. I await your calls. And if you don't want to call me...I have some other interested medical geneticists who would love to help....

The Sherpa Says:

There are several solutions to all of these issues. All of them flow through licensed physicians and medical care. Trust me....I am starting to feel like Cassandra at least towards these CEOs! For the consumers, fear not. We will get physicians and other healthcare providers up to speed. I promise. Until then, call me.

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?

GINA needs you!!!

From my gmail today...news that the GINA may reach the floor of the senate this week!!!

This is it! GINA may go to the Senate floor this week!

Take action to secure success for GINA

The Senate may consider the Genetic Information Nondiscrimination Act (GINA) as early as the week of April 14th! This legislation provides fundamental protections against the misuse of genetic information in health insurance and employment decisions.

We need your support to make sure GINA is successful.

Please take 5 minutes or less to make the following 3 phone calls.

A staff member will answer and take the call:

Call Senator Reid at 202.224.3542 and thank him for his support of GINA.

Sample script "My name is (YOUR NAME) and I am calling to thank Senator Reid for his leadership on the Genetic Information Nondiscrimination Act, or GINA. I would like to encourage him to take swift action to ensure GINA's success. Thank you!"

Call your two senators and ask them to support GINA. You can find their names and contact information at http://geneticalliance.org/senator.list

Sample script "My name is (YOUR NAME) and I am a constituent of (NAME OF SENATOR). I am calling to ask for (NAME OF SENATOR).s support for the Genetic Information Nondiscrimination Act, or GINA, and all the procedural motions needed to support this legislation. This legislation provides fundamental protections against the misuse of genetic information in health insurance and employment decisions. It is vital for all Americans to have these basic protections. Thank you!"

Thank you for your support,

Joann A. Boughman, Ph.D.Executive Vice PresidentAmerican Society of Human Genetics

The Sherpa Says:

What are you waiting for? Call Now!!!!

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.

OK for Journals but Cut From the LA Times

It is important for all of us to contribute to the literature and assure the success of new and upcoming journals. I want to point you in the direction of 2 of these journals published by Future Medicine in London.

I mention this because I just finished my manuscript for The Journal entitled Personalized Medicine. This is an excellent journal with a tremendous potential. I recently published here and intend to send a significant amount of my work its way. But what is most important about these journals, Pharmacogenomics and Personalized Medicine, is that they are giving an opportunity for younger scientists, physicians and stake holders a voice.

This is important especially because as we interview with reporters, there is no guarantees that it will end up in their article. BTW Anna, I loved the article. Anna Gosline wrote an LA Times article which she spoke with me about. Well, I guess Muin is a bigger name than me ;)

Everyone should read this article....It is excellent. And Anna, if you need some medical advice feel free to call us and you can be one of our cadre of Navigenics patients.

I have recently begun to realize the potential of pairing patient centered care with genomic medicine. By putting these two ideas together....we may have a winner. I think that these two parallel ideals may actually be synergistic. Put plainly, moving the care in a patient centered way that DOES NOT REMOVE the healthcare practitioner, but places them as the coach, enables patients to make better choices by understanding their genomic risk. First by taking a family history and secondly by using appropriate genetic testing. Just like Muin said.

Ok, now the gossip fix. Did anyone read the Sunday Times? Well Navigenics was in it. Slapping 23andMe in the face. From the article

The company has been authorized to sell the service to residents of every state except New York (Told you so), Ms. DuRoss said. New York residents must join a waiting list until state health officials license the company’s designated lab to provide services to New Yorkers.

Even if that regulatory hurdle had been cleared, Ms. DuRoss said she doubted that the company would have invited customers to provide saliva samples on the spot. “It’s a little awkward to ask people to spit in public,” Ms. DuRoss said. “It’s a very private thing.”

Woah!!! We (Navigenics) are classy and tactful, You (23andME) are classless. That's what it sounds like to me ;)

The Sherpa Says:
When my next article is published I will let you know. I hope it serves as a good compass. Speaking of compass, take a looksie at Daniel's post at Genetic Future....he seems to think these big corporate genomic companies will be fighting each other for quite some time....He may be right. Maybe they could read my article? Then they would realize what they needed to do. Differentiating themselves is definitely a start.

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!

Al Gore and WebMD

I want to take the moment and laud Navigenics. Yes...as I am hard on all. I am equally fair. I recently took their wonderfully funded CME course on WebMD. I am so very impressed with their desire to educate physicians.

This is the key to the provision of Genomic Medicine. I am currently working on an article about corporate genomics, brick and mortar services, and what is often called Patient Centered Care. The crux of my theory is that nothing will move forward without the education of health care providers. So Bravo to Navigenics....I have been very hard on you in the past. Just as I have been hard on other companies like 23andME and deCode. I am certain that I am hated in Iceland or Forbes.

In addition, by funding a study at Mayo regarding how patients interpret these results you are going to contribute to the line of literature which indicates that physicians can't even interpret the test results....so I applaud you for distinguishing yourself from your competition. When will 23andME follow your suit? deCode?

We are all in the same industry. To be fair, I just am hard on all. I hope you ALL understand and know that I am here to protect the patient and provider first. That is my charge. We have a large mountain to climb and anything that smells like Scientific Match.Com should get taken out with the rest of the garbage at basecamp.

Lastly,

A little birdy told me you had Al Gore on Monday? How come your PR people did not get that in the NYT????? He is after all a partner at KP.

-Steve

Back to the Basics.

I used to play football and had a coach who said "If you block and tackle better than anyone, then you will win championships"

I thought he was crazy. I thought you had to have super talent to win. But year after year it is clear in the NFL that teams who block and tackle better...win. You know this to be true in all sports.

So here at the Gene Sherpa, I am going back to the basics. I have been getting away from that and being a little preachy and in fact turning into a tabloid...While it does generate alot of blog hits.....Searches for Navigenics has sent my hit rate rocketing on FeedBurner....I think we need to report on how we are doing in our progression to Genomic Medicine.

So when I open this month's edition of Internal Medicine News "The Leading Independant Newspaper for the Internist-Since 1968" it is nice to see several headlines involving genetics. But it is sad to see the front page reading "Help Wanted: Internists Needed"

Yes it is true, there is a lack of primary care providers and it is only getting worse. They are suffering from the same problem as the medical geneticist. Not enough pay for the value of services provide....

But there is some good news, Primary Prevention works. We are already seeing the benefits of the HPV vaccine reducing the incidents of abnormal pap smears. HPV is a virus which causes cervical cancer. The first signs of an abnormal cervix are found on a Pap smear. In fact a reduction in cervical biposy of 22% is a very big sign we are headed in the right direction. Imagine that....Vaccines work.

In addition to all of the Genetic/Genomic Centered articles there is a subsection which I had mentioned in prior posts called "Genetics in Your Practice". In this section the cover connective tissue disorders like Marfan Syndrome. This is especially timely after the lawsuit involving John Ritter's death. Aortic Aneurysms are genetic and familial. In fact we have seen patients with such conditions. Timely detection by ultrasound can avert sudden death. It is important to pick up the subtle clues by taking a family history. Often a referral to a Medical Geneticist may aid in the diagnosis and treatment.

This is not to say we always get it right. We were wrong about the intitial pathogenesis of Marfan Syndrome....but now we know "better".

Often, I have heard a comment about "Outliving" BRCA risk. We know that BRCA cancers are often earlier onset. We also say that their penetrance (ability to cause disease) is not 100%. Meaning, not all people with BRCA mutations get disease. But, we may be wrong.....In a new study of postmenopausal women with BRCA mutations, Dr Tice of UCSF reported on 114 BRCA 1 and 90 BRCA2 women who were unaffected by age 55. From he study he concluded and validated this fact. Women with BRCA1 or BRCA2 mutations who are unaffected at 55 years old. Mutation still confers a lifetime risk of breast and ovarian cancer of 50%....

Outlive risk??? Huh....Wrong again. Interestingly enough, most prophylactic mastectomies and oophorectomies are done in women younger than 55. Is this because most BRCA diagnosis are in younger women. Well when analyzing the raw percentages, it turns out uptake is twice as great in women younger than 55....Maybe it is because some geneticists and counselors are telling the patients about "Outliving" the risk. I guess they over credited those modifier genes.....Or maybe they didn't see a genetics professional at all. This can be a big problem with H/O specialists. Oh and Bradbury's study the average age of the 88 studied was 42 years old...hardly old enough. I still cannot find how may were over 55. In that study, older age was considered older than 40!

Ok, so here's the skinny on the Navigenics cocktail parties. Around 50 people were there last night. Alot were employees of the company. Opening night a head count of 90. Different from the reported count. Here's the kicker.....open bar, good looking bartenders, good discussions...... There, I have sated my tabloid fix

The Sherpa Says:

Those who climb the mountain on a weekly basis must not get too arrogant. The mountain can punish you as well.

A New Hope

I just got out of a meeting with a Very Nice Angel Investor. He had some really interesting ideas that I am dying to tell you about....but I just can't.....for now.

But what I can do is now tell you about how sad I am that I missed "Navigenics 2008 Opening Day" I don't know who was pitching...but from what I heard it was a success. Speaking of success, I just had another patient come to me with the magic 84 page printout. It will be interesting to see how the Mayo study comes out regarding all of these lab reports and patient comprehension. A few days ago a patient was seen by us for Pharmacogenomic analysis and he was puzzled by the laboratory reports and data. He actually thought that the boiler plate information on the bottom of the report was actually personalized. He asked "If I only have 2 copies of this, then why does it have 9 different types on my report?" I kindly reported that it was the boilerplate explaining all of the poor metabolizing alleles. Of which this patient had 2. Yes reading lab reports can even be tricky for physicians. Think it has changed since the 90s? Dream on!

It is no surprise that genetic counselors are on staff at Navigenics. It is the right thing to do....but how many genetic counselors know what CYP 450 is? Oh I mean what CYP 450 are. How in the world can we reconcile this? Even better question....how may physicians know what CYP 450 are? But there is a new hope. An institution being set up by myself and others. We are currently looking for donors and we endeavor to set up educational events and group sessions. We will work with Corporate Genomics, Academic Genetics, Corporate Labs, Academic Medicine to develop training workshops. Interested???? Email me.

This type of education is the future. We need to walk patients and physicians through reports, through taking family histories, through medications....together. Preferably face to face or television to television. It is my belief that we cannot do this through a scalable 84 page report....or a Flash'd/XML'd out site. No amount of money will replace the human element. So we need to train more Sherpas....and I am looking for funding to do it.

The Sherpa Says:

I am headed to SoHo tonight. Maybe they will have a million or two lying around???? After all, this is a new industry ;)

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

T minus 21 hours

Till Navigenics Launch.......
Stay Tuned!
-Steve
p.s. Congrats to Amy over at....oh wait...she hasn't started a blog yet ;) But in all seriousness, congratulations. Thanks to Jonathan at Tree of Life for leaking this......

DVPMP and Me

So today I want to ask all of you a question. Is there a conflict of interests if I participate in the Delaware Valley Personalized Medicine Project and sit on its Informed Cohort Board? I have been giving this some thought lately....

This is a wonderful project with some very secure privacy measures akin to Swiss Banking. Unlike other Direct To Consumer projects this is Funded. Unlike others we will be evaluating on a rolling basis and releasing data that is reviewed by our board. I would love to participate.

So I ask.....would it be a conflict if I reviewed the data AND had submitted a sample?

If I paid for the 23andME or deCodeMe would I have reviewed my OWN data. You are damned right I would. So what makes this different? I would be reviewing and commenting on others' data too. The important point is that we only release medically actionable information after we have discussed it. So in essence I would be blinded to my data until after we had reviewed the studies.

So........

I ask....."What do you think?"

Jessica Queller and BRCA1

First I would like to apologize to Spiegel and Grau. I missed you gracious letter. Please give me a call.


Second.....I am catching some serious heat about the deCode rant! I never knew so many smokers were hoping to escape cancer and angrily flaming me with emails. Here's a hint ladies and Gentlemen........Quit Smoking and maybe you will avoid cancer. To all of those who decided to fill my gmail yesterday....thanks for reading this blog. I appreciate your interest.


I don't know how many of you picked up the USA Today on March 31st, but in it was a profile on Jessica Queller. She has written a book called:

Pretty Is What Changes-Impossible Choices, The Breast Cancer Gene, and How I Defied My Destiny

About the Book....
Eleven months after her mother succumbs to cancer, Jessica Queller has herself tested for the BRCA “breast cancer” gene mutation. The results come back positive, putting her at a terrifyingly elevated risk of developing breast cancer before the age of fifty and ovarian cancer in her lifetime.
Thirty-four, unattached, and yearning for marriage and a family of her own, Queller faces an agonizing choice: a lifetime of vigilant screenings and a commitment to fight the disease when caught, or its radical alternative—a prophylactic double mastectomy that would effectively restore life to her, even as it would challenge her most closely held beliefs about body image, identity, and sexuality.

The Sherpa Says:
To understand the human issues surrouding genetics we need to experience or read others' experiences. I think many of you already know of my family's history.....very similar.
I am hoping to invite Jessica to the blog. Wish me luck.....

Safe to Smoke? Bull$h!*

I am so pissed off this morning. Mainly because of the assault that must be led by Phillip Morris, DeCode and the Devil Himself.

In a recent press push.....from as far as I can see. There is now a "magic bullet" for smoking and avoiding cancer. Recently published data in the Journal Nature is being over hyped. From Good Morning America to Fox News to MSNBC to my friend Hsien at Eye on DNA (Well hers isn't so much hype)

From Her blog

All three studies identified regions on chromsome 15 that are associated with nicotine dependence, lung cancer, and peripheral artery disease. The deCODE study focused on SNP rs1051730 located on chromosome 15q24 in the CHRNA3 nicotine acetylcholine receptor. People with one copy of the “T” version of this SNP had:

30% increase in risk of lung cancer OR of 1.3
20% increase in risk of peripheral artery disease OR of 1.2

Half of people of European descent have at least one copy of the higher risk SNP and 10% may have two copies which increases their cancer risk by 80%...... OR of 1.8

From the Nature Report
Tobacco is thought to be responsible for about 5 million premature deaths every year and smoking is still clearly the largest risk factor. But the new results suggest that, amongst smokers, some people may be as much as 80% more at risk than others thanks to their genes.

A solid analysis...but there are some old statistics out there that you need to know...
First, in the quoted 80% study the Odds Ratio of cancer in Homozygotes was 1.8. OR of 1.8 equals an increased risk of 80%.....That is small potatoes. Why? See here.

Well, In an environmental analysis in 1990 it was found that children exposed to Household exposure to 25 or more smoker-years during childhood and adolescence doubled the risk of lung cancer an odds ratio of 2.07. Obviously genotype was not evaluated.

So why is this group of smokers likely to quit if they even won't quit to prevent their children from getting cancer? Just chalk it up to the genes!

So what is the risk of cancer for smokers? You should go to the NCI website and see for yourself.

Is this a worth while genetic test? No. The risk of head and neck cancer, something smokers get too is skyrocketed in the face of family history or alcohol consumption. If you think 80% is high, try 4200%....... naive reporters (Except for you Amy, sorry to bash your colleagues) To predict lung cancer risk more accurately, try the M.D.Anderson Model.

Why is this study and the press surrounding it silly and misleading? Because smoking causes more than just lung cancer......The study should have included all cancers....in that case you would have found much more interesting results...

The Sherpa Says:
Bottom Line, if deCode comes out and markets this test they should be shot. If they do sell it, it is only a sign of how absolutely horrible the financial position they are in. Smokers don't need further encouragement to keep smoking.....It is hazardous to them and the ones they love. Just quit....most people can't stand your smoke or paying for your cancers.... Here's to NY!

CLIA? What's that????

You gotta love the shenanigans of these supposed non-clinical SNP Chip testing companies.....Yes, I have decided to call them what they are. They are not Genome Testing companies, they are SNP chip testing companies and guess what? Linda and Anne ran into a buzz saw or maybe revealed their true intentions the other day. Thanks to Daniel over at Genetic Future for pointing this "D'Oh" out......

It turns out that the lab where they had been testing YOUR DNA....Well, not really because when you sent it to them it became THEIR DNA. It turns out that they are not CLIA certified. What is CLIA?

From the Website

Background

• Congress passed the Clinical Laboratory Improvement Amendments (CLIA) in 1988 establishing quality standards for all laboratory testing to ensure the accuracy, reliability and timeliness of patient test results regardless of where the test was performed.
  


• A laboratory is defined as any facility which performs laboratory testing on specimens derived from humans for the purpose of providing information for the diagnosis, prevention, treatment of disease, or impairment of, or assessment of health.
  


• CLIA is user fee funded; therefore, all costs of administering the program must be covered by the regulated facilities.
  


• Centers for Medicare & Medicaid Services (CMS) (formerly Health Care Financing Administration) assumes primary responsibility for financial management operations of the CLIA program.

The real story....using a non-CLIA certified labs means that no one is held accountable to quality standards or reliability testing. CLIA serves to protect patients.....As Homer would say "D'Oh!"

So anyone who got the 23 and Me test prior to the supposed switch should not be too sure about that Ancestry Painting...And that outlaw streak in you may just not be attributed to the "supposed" link with Jesse James

They say

Though CLIA certification and oversight are appropriate for specific health and disease-related testing, we are complying with these guidelines to be consistent with other types of laboratory testing.

This switch does not affect in any way the nature or quality of the information we provide. We are still using the same technology as before. However, the transition from one lab to another has resulted in delays that are temporarily increasing the length of time it takes to process customer samples.

At no time have we experienced any problems with data quality. We are confident, after comparing genome scans from the previous and new laboratories, that they produce consistent information at greater than 99.9 percent accuracy. That means customers who had their samples processed before the switch will not be at a disadvantage now or in the future.

0.1% isn't that a whole ton of SNPs?????

The Sherpa Says:

Clinical laboratory testing certification is the LAW for health care providers.....Why would 23 and Me need to scramble and use a CLIA certified lab? Hmmmmmmm..........Navigenics? Can you hear me? Me Thinks You have some competition coming........And to the Ladies of Mountain View......Prove It!.....Offer to resequence all the customers who previously tested PRIOR to the switch and then allow them to compare new results with the old results! Oh and BTW.....in New York you need NYS certification too.......Betcha Affy forgot to tell you that.

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.